Lipids -stored in adipose cells of animals, long term energy storage, chem messenger
(hormones), insulation/cushioning, structure (phospholipid membrane)
Why are lipids well suited for long term energy storage?
● high energy bonds between carbon and hydrogen
● 2x energy/gram than carbohydrates (concentrated more compact)
Five Forms:
1) Fat: Triglyceride / Triacylglycerol
Glycerol
+
3C chain, each with
hydroxyl (OH)
3 Fatty Acid Chains (via anabolism/dehydration/ condensation)
- 4-24C unbranched chain w/carboxylic acid (COOH) at one end
-classified by #of carbons and saturation (double bonds)
*hydroxyl from glycerol reacts w/carboxyl on fatty acid, forms ester bond*
Fatty Acid Properties
Saturated: max # of H atoms, all single bonds, solid@rt, from animals (lard/butter)
(Mono/poly)Unsaturated: double bonds, liquid@rt, (mono-olive oil, poly- sunflower)
Fluidity: longer chain = more hydrophobic = less fluid, unsaturated = less fluid
2) Phospholipid =Glycerol, 2 fatty acid, 1 phosphate (w/polar head group): amphipathic
Polar Head: negative polarity, hydrophilic
Non-Polar Tail: No polarity, hydrophobic
Phospholipid Self-Assembly: spontaneous, in water due to hydrophobic interactions
-form micelle, single layer of phospholipid, polar heads outward, nonp tails inward
-Phospholipid bilayer is a double layer of phospholipids where the nonpolar tails
aggregate forming a hydrophobic core; basic structure of plasma membrane
3) Steroid= 3 6C rings + 15C ring; cholesterol, hormones (estrogen/testosterone)
4) Wax= long chain hydrocarbons
● Primarily wax esters: a long chain hydrocarbon with an ester group that is not a
triglyceride (could also involve alcohol, aldehyde & ketone groups)
● plastic properties; deforms under pressure w/no heat, solid@rt, liquid under heat
● thermoplastic: polymer that becomes a liquid when heated, glassy when frozen
● Natural: animal (bees, shellac) vegetable (soy, jojoba) mineral (fossil fuels)
● Synthetic: polyethylene, polypropylene
5) Carotenoid= natural fat-soluble pigment: vitamin A, antioxident
● 40C alternating double/single bonds, terminated w/cyclic groups
● in photosynthetic material: plants, algae, used to absorb light (beta carotene)
Enzymes- biological catalyst (speeds reaction rate→ fast enough to support life)
-made of proteins, not ribozyme [made of RNA] hydrolysis @ phosphodiester bond of RNA
-ends with ‘ase’, root suggests its substrate ex. ATPase
Catalyst: chem agent, changes rate of a reaction, not consumed by reaction (reusable)
Substrate: reactant that enzyme acts on
Active Site: pocket where substrate binds & is converted to product
-R Groups on amino acid of enzyme interact with the substrate @active site
Catalytic Reaction: bond breaking + forming
● Change in Free Energy (ΔG): energy diff btwn prods and reactants (exergonic -ΔG)
● Exergonic: releases energy, needs activation energy to break bonds, (uses heat)
● Activation Energy: amt of energy needed to push reactants over energy barrier
○ heat=agitation=instability; peak of instability = transition state
**Enzymes lower EA, do not affect ΔG** MSCOv
● active site brings reactants closer + in correct orientation 4 reaction
● strains bond/puts under stress, easier to break
● R-groups provide appropriate microenvironment
● bind covalently to substrates in intermediate step b4 returning to normal
○ properly orientates substrate, changes chem at active site
Sequence of Events: E + S→ ES→ES*(transition)→EP→E + P | E+S
substrate binds to active site→form enzyme substrate complex→ enzyme envelopes substrate→ enzyme
product complex→ products lose affinity for site | enzyme available for another S
Enzyme Specificity
● Substrate specific: recognizes one substrate only; even differentiates enantiomers
○
●
Induced-Fit Model: enzyme changes shape for better fit w/binding substrate
○
●
Exception: racemase (an isomerase) that can convert for each enantiomer
binding induces a favourable change in the shape of the active site
Reaction Specific: enzyme specific to one chemical reaction (sucrase/hydrolysis)
○ *metabolic enzymes: most can do forward+reverse reaction*
Factors Affecting Enzymatic Rate of Reaction [S]T°ApH
● single enzyme can catalyze thousands or more reactions a second
● Substrate Concentration: more substrate [S] = faster binding speed
○ Enzyme Saturation: active sites on all enzymes are engaged: can only increase
productivity by adding more enzyme molecules (rate slows when reaching
saturation bc all enzymes are at max potential)
● Temperature: high temp = more collisions = faster rate
○ each enzyme has optimal temp; temp too high = denaturation
● pH:optimal pH (most btwn 6-8) (stomach: 2) (intestine: 8)
● Availability of Cofactors: more readily available = faster rate
Enzyme Regulation
Inhibition- molecule binds to an enzyme, prevents from catalysing reactions: irreversible if
covalent bonds involved, if bonds are weak = reversible (metabolism reg) -exist for negative
feedback, maintain homeostasis
Competitive: same site as substrate, sat curve reaches saturation, takes longer
○
antabuse competes w/aldehyde oxidase-prevents acetaldehyde→acetic
acid=build up of acetaldehyde (feeling of hangover, pill deters alcoholism)
Noncompetitive: binds elsewhere; makes enzyme insensitive to substrate by interfering
w/active site/altering enzyme conformation; less receptive/effective
○ sat curve will NOT reach saturation; %inhibitor = %decrease in reaction rate
Allosteric Regulation- effector attaches to another site, not the active site of enzyme
Allosteric Site: specific binding site on enzyme for effector, not active site
Allosteric Enzyme: has allosteric site, changes btwn (in)/active conformation
Allosteric Activation: stabilizes conformation that has a functional active site
Allosteric Inhibition: stabilizes conformation that lacks active site [inactive]
Cooperativity: allosteric site is located between subunits, binding of one effector could
stabilize the conformation of all subunits; requires multiple subunits
● positive coop: activation, negative coop: inhibition
Macromolecule Indicators
Iodine-starch, yellow→black-blue
Benedict’s Reagent- reducing sugar, bright blue→dark orange/red
Biuret- protein, pale blue→deep violet
Sudan IV- test for lipids, clear→dark red/orange (not water soluble, but lipid soluble)
Proteins
Amino Acid (Monomer): sometimes referred to as residue,
● Amine (NH2), Carboxylic Acid (COOH), H Atom, R-group on chiral carbon
● Amphiprotic: has acid+base qualities
○ ionized form observed in aqueous bc acid donates H+ to base (NH+3, COO-)
● 20 Amino Acids: defined by R-group, 8 are essential: cannot be made by body
○ Polar R: ends w/OH, SH, or amide (CONH)
○ Non Polar R: end in Cs, C rings (hydrophobic)
○ Acidic: neg charged ions (COO-)
○ Basic: pos charged ions (NH2/3) (more H)
Primary Structure: polypeptide chain, unique sequence
● condensation/dehydration of 2 amino acid groups (N+C terminus required)
○ forms peptide bond, amide | backbone = everything but the R-groups
●
determines shape→function, thus binding (ex. antibodies enzymes neurotransmit)
○ slight change can be bad, ex. sickle cell anemia;hemo crystallizes+cells clot
Secondary Structure: alpha helix, beta pleated sheets (coils/folds; not all proteins have)
● due to H bonds at reg intervals along pep backbone
Tertiary Structure: interactions btwn R groups and/or backbone
● Hydrogen/Ionic bonds/Hydrophobic Interactions (interior of protein)
●
Covalent bonds: disulfide bridge: 2 (SH) of cysteine amino acid → S-S
● Proline Kink: only amino w/R group attached to amino, forms natural kink
Quaternary Structure: aggregation of 2+ polypeptide subunits
● Globular: spherical, water soluble (hemogoblin)
● Fibrous: threadlike, water-insoluble, (collagen, structure, 2 pep supercoiled)
Protein Folding: spontaneous, aided by chaperonin which provides ideal environment
Conformational Change: reversible shape change,still functional, in response to physical +
chem conditions, part of protein’s function ex. carrier protein
Denaturation: shape change, disturb function, irreversible, alt in environ (pH, salt, temp,)
● ex. egg white
Renaturation: some can return to functional shape aft denaturation, others can’t in crowded
environment of cell
Nucleic Acids- information/gene storage, identical copies possible, evolution evidence
● chem energy (ATP), form enzyme w/other groups, signal molecule
Nucleotide (Monomer): DRAW THIS
● sugar + base + phosphate
● Pentose Sugar (2: Ribose/Deoxyribose)
○ 5C, all have OH on ribose, deoxy- OH on 2’ is missing
● Nitrogenous Base (5: Adenine, Guanine, Thymine, Uracil, Cytosine)
○ Purine (AG): 6C+5C, Pyramidine (TUC): 6C
○ AT = 2 H Bonds, CG = 3 H bonds
● Nucleoside: base+sugar; glycosidic N-bond: 1’ OH on sugar and H on base (dehy)
○ A: Adenosine G: Guanosine
○ C: Cytidine T: Thymidine U: Uridine
(add deoxy if on deoxyribose)
● Phosphate (1-3 P molecules: mono, di, tri)
○ attached to sugar of nucleoside at 5’
Nucleotide Nomenclature: nucleoside name + prefix + phosphate
● Example: adenosine triphosphate = ATP
● Example: Nucleotide that has a pyrimidine base that forms 3 H‐ bonds, a deoxyribose
sugar and 2 phosphate groups: deoxycytidine diphosphate = dCDP
Nucleic Acid Building
● Single:5’s phosphate’s OH + 3’s OH form a phosphodiester bond via dehydration
●
backbone: phosphate→ 5’ → 4’ → 3’
●
DNA Double Helix: 2 non-parallel (3’-5’) strands held w/base pairs (AT/CG)
○ ladder: sugar/phosphate = sides, rungs = H bond btwn base pairs
○ overall negative charge: phosphate groups (PO3-)
Carbs- booklet
Membrane Structure
Plasma Membrane- phospholipid bilayer, each layer = leaflet
● Hydrophobic core is formed as a result of water surrounding the phospolipids
● “Fluid Mosaic Model”: fluid movement, mosaic: membrane has diff molecules
Fluidity is affected by:
(Singer and Nicolson 1972)
○ Saturation: double bonds prevent tight packing
○ Hydrophobic Restrictions: lateral: same leaflet | flip-flop: rare, opp leaflet
■ Asymmetry: leaflet facing inside is diff than the other; restrictions in the
flip-flop motion help maintain this asymmetry
○ Cholesterol: large: interrupt inter-m attraction | non-polar: stabilize hydrophobic
■ large @ low temp, non-polar @ high temp
Mosaic: integral+peripheral membrane proteins carbs, cholesterol
Integral Membrane Proteins- spans the entire width of the bilayer
● most are transporter proteins (carrier, channel), work in facilitated transport
● Channel: help small opp charged ions cross hydrophobic core, tunnel-like
● Carrier: moves large uncharged molecules by conformational change, gate/door
Peripheral Membrane Proteins- non-covalently bound to either side of membrane
● extracellular: communication, receptor/recognition proteins (antigen/glycoprotein)
● intracellular: structural support, cytoskeletal protein immobilized on membrane, attached
to cytoskeleton
Carbohydrates- extracellular, signals + help other cells recognise it
● Glycoprotein: carbohydrate + protein Glycolipid: carbohydrate + lipid (phospholipid)
Phospholipid Layer: Draw Diagram
Membrane Function- (solute is dissolved, solvent is larger)
●
maintain internal cell environment, similar to homeostasis@cell lvl, selective barrier
Passive Transport- no energy required, high→ low conc, collision theory
Simple Diffusion: small neutral molecules (O2 CO2), no need for membrane proteins
● molecules move across semi-permeable membrane/down conc gradient
● continues until equilibrium is reached | osmosis in lab setting
Facilitated Transport: requires channel/carrier transport proteins
● channel proteins move small charged particles (ions) through the hydrophobic core
○ must be oppositely charged, tunnel-like
○ Aquaporins: channel protein, facilitates water movement in natural osmosis
● carrier proteins move large uncharged molecules (ex. glucose)
○ change conformation/shape, act like gate/door
Osmosis: water will move to dilute solute, high → low water conc.
●
Tonicity: osmotic pressure due to the diff in conc across semipermeable membrane
○ influenced by solutes that can’t pass the membrane from outside of cell
○ Isotonic: water:solute ratio is same out and inside, equal movement in+out
■ equilibrium in animal + blood cells
■ plant cell: flaccid
○ Hypotonic: less solute:water outside, water moves into cell
■ osmotic lysis (expansion+burst) in animal, hemolysis in blood cells
■ plant cell: turgid/swelling (normal), internal pressure up bc water entry
○ Hypertonic: more solute:water outside, water moves out of cell
■ cell shrinks in animal, crenation in blood cells
■ plant cell: plasmolysis, membrane/cytoplasm shrink from cell wall
Active Transport- ATP required, low to high concentration/against gradient of pump
●
●
●
requires a pump transport protein, ATP causes conformational change
Coupled transport is possible w/some pumps (sym+antiport)
EX. Na-K pump: antiport, oscillates btwn 2 shapes; 3Na out, 2K in
Direction of Transport: Active + Passive Only
●
●
●
Uniport: single molecule in 1 direction (channel)
Symport: 2 molecules in same direction (Na/Glucose symporter)
Antiport: 2 molecules in opp directions (Na/K pump)
Bulk Membrane- transports molecules too huge/polar to pass through membrane
● cell membrane folds in to form vesicles
Endocytosis: entry to the cell
● Phagocytosis: cellular eating; large particles/cells are ingested
○ simple life: digestion, complex: defence against foreign particles
○ Phagocyte: white blood cell, ingest foreign substances
● 1) Pseudopodia (extension) wraps around a particle to engulf it into the cell
● 2) Phagosome encloses particle in itself; a large sac, size of a vacoule
● 3) Phagolysosome results when a phagosome and lysosome merge
● 4) Hydrolytic enzymes from lysosome digest the particle
● 5) Residual body, has indigestible material, discharged by exocytosis
● Pinocytosis: cellular drinking, dissolved substances are invaginated (inward fold)
○ occurs in most cell types, unspecific
●
●
●
●
●
●
●
Receptor-Mediated: intake of molecules that bind to a specific receptor on cell
○ Ligand- molecule that binds to a receptor protein
○ Coated Pits- Clustered receptor proteins on membrane which has
Coat Proteins- helps form vesicles for endocytosis
1) Ligand binds to receptor
2) Membrane pinches to form vesicle
3) Ligand detaches from receptors
4) Vesicle pinches into 2 parts: free ligand, empty receptor
5) Ligands fuse with lysosome
6) Receptors return to cell surface
Exocytosis: movement of materials from cell to cell surface in membrane bound vesicles
● vesicles formed by Golgi or from endocytosis, function for: Secretion: release of waste,
toxins, signaling molecules Recycling membrane proteins Restoring cell membrane;
membrane SA needs to be constant (balance endo) SRR
Molecular Mechanisms: Historical Experiments
Meselsohn & Stahl- discovered which DNA model of replication was true
Conservative: 1 daughter is the parent, 1 daughter is newly synthesized
Semi Conservative: both daughters have 1 parent strand, 1 newly synthesized
Dispersive: daughter duplex made of segments of parent and newly synthesized DNA
1) Grew E. Coli cells in heavy nitrogen (15N>14N), DNA has nitrogen bases
2) Transferred to 14N medium, 1 round of replication, density gradient centrifuged
a) conservative: show 2 bands, semi+dispersive: show 1 band (saw 1 band)
3) Another round of replication in the 14N medium, density gradient centrifuged
a) semi: 2 bands (14/14,14/15) dispersive: 1 band [conservative: 15/15 14/14]
Garrod- first to suggest genes affected chemical reactions in metabolic pathway
●
genes → enzymes → phenotype
●
Alkaptonuria: buildup of homogentisic acid causes black urine
○
individuals lack enzyme to break down alkapton (no enzyme→alkaptonuria)
○
thus symptoms of inherited disease (inheritance→no enzyme→symptoms)
○
genes dictate phenotypes via enzymes (genes→enzymes→phenotype)
○
hypothesis based on chem rxns taking place in steps (metabolic path)
Beadle & Tatum- “one gene one enzyme hypothesis”, based on^ (wrong; code for others too)
● used bread mold bc short life cycle, can grow on minimal media
● hypothesis: bread mold has all enzymes to make all amino acids (no essential)
○ test by mutating (x-rays), isolate; see if can grow in complete, not minimal, test
which amino mold couldn't make [minimal+1 amino (arginine)]; grew
○ pathway responsible for arginine broken; bc enzymes; genes responsible
○ further isolated mutant to identify which step in pathway was broken
○ metabolic diseases- inherited+gene funct. dictate production of enzyme
○ one gene one protein: not all enzymes are proteins, some RNA (ribozymes)
○ one gene one polypep: protein may have more than 1 subunit
○ some genes don’t make polypeptides, one can produce multiple (splicing)
Watson & Crick- Central Dogma:DNA<-->RNA→Protein
Model
Sequence Hypothesis
Central Dogma
Contributor
Watson (1965)
Crick (1958)
Statement
Positive: transfers from nucleic
acid to protein exists
Negative: transfers from protein to
nucleic acid do NOT exist
Marshall Nirenberg- deciphered first codon, Nobel Prize for interpretation of genetic code
● synthesized artificial mRNA w/identical RNA nucleotides, 1 codon (ex. UUUUUUU)
● result: 1 type of polypeptide (phenylalanine), experiment repeated w/other bases
Replication-base pairing lets DNA strands be templates for complementary strands
DNA Replication Complex: anchored to fibres of nucleus, pulls in parent strands
Initiation: starts at ori, single ori in prokaryotes, multiple in eukaryotes fuse; bidirectional
● Helicase: separates DNA templates at replication forks, disrupts H bonds
● SSBP: bind to unwound single strand DNA to keep them apart in replication
● Topoisomerase: relieve tension in DNA due to unwinding; snips/glues together
● Primase (RNAP): adds primer, only needs template, makes 3’OH for DNAP
○ Eukaryotes: 15+ DNAP (greek letters), Prokaryotes: 5 (roman numerals)
Elongation:
●
DNAP III: catalyses elongation of DNA by adding nucleotides to 3’OH (5’ → 3’)
○
w/addition of new nucleotides 2 P groups hydrolyzed into pyrophosphate
●
DNAP I: replaces RNA primer w/DNA complementary to template (5’ → 3’)
●
antiparallel DNA→leading/lagging strand (okazaki fragments: 1000-2000 nucleotides)
●
Ligase: catalyses missing phosphodiester bonds
Termination: ends at end of chromosome or if bubble/fork meets another bubble/fork
DNA Repair/Proofreading (1/109 final error, 1/10000 initial=15000 errors per replication)
● Mismatch (uncorrect pair), Missing bases, Fused bases
●
UV light→pyrimidine dimers (fused TT); Xeroderma Pigmentosum- can’t repair
●
Nuclease: breaks phosphodiester bonds in DNA + excises out the nucleotide
Nucleotide Excision Repair (NER)
○ endonuclease binds to middle of chain, DNAP fills gap, ligase seals
○ exonuclease: binds to ends 5/3, in DNAP I+III, instantaneous
■ DNAP recognises mismatches + replaces nucleotide upon excision
Telomeres- get shorter after every replication bc lagging strand needs primers
● at end of chromosome, non-coding, multiple repeats of same sequence
● prevents erosion, more of a protective cap to prevent unwinding
○ uncapping/shortening is sensed, if too short, it will stop dividing (senescence) or
self-destruct (apoptosis)
●
conception:15000 bp, birth:10000 bp, death:5000bp → added before fertilization
●
Telomerase- (ribonucleoprotein) adds telomeres via reverse transcriptase
○ extends 3’ parent- reverse transcribes w/internal RNA template (repeats)
○ primase add primer, DNAP alpha elongates| human- int: AAUCCC-TTAGGG
○ cells live longer w/telomerase, this is why somatic cells are finite
Telomeres are only added to germ cells, cancer cells’ telomeres don’t erode
○ added to germ cells bc baby would die via replication if not long enough
●
Transcription- DNA→mRNA
Gene: stretch of DNA which is transcribed; transcription unit
Promoter: where RNAP II first binds, upstream, AT rich (2 H-bonds, easier to unwind)
● transcription start point, Pro: Pribnow (-10) TATAAT, Eu: TATA (-25) TATAAA
Initiation: Pro: RNAP recognises/binds to promoter, Eu: transcription factors bind prior
● Transcription initiation complex: eukaryotes only, if TF+RNAP are both on promotor
● TF: some control how often genes are transcribed
Elongation: RNAP unwinds 10-20 bases+adds comp. RNA bases, DNA reforms behind
● many RNAP can transcribe simultaneously
● Coding = Sense, Non-Coding = antisense = template, transcript = new RNA
Termination: terminator sequence (transcribed) Eu: AAUAAA
● Pro: stop at sig | Eu: RNAP continues 100s of bases, mRNA released 10-35 aft sig
RNA Processing- Eukaryotes Only
Post-Transcriptional Modifications (5’ cap, polyA tail; prevent degradation)
● 5’ Cap: modded guanine, signals ribosome attachment
● PolyA: 50-250A tail to 3’ added by polyA polymerase, help export mRNA from nucleus
Splicing: removal of introns: intervening (noncoding) sequences, interspersed btwn exons
● exons: coding regions, expressed (except leader 5’ UTR + trailer 3’ UTR)
● splice site: at end of intron snRNP/snurps bind (ribonucleoprotein/ribozyme)
● snRNP: excises intron, rejoins exons
● Co-Transcriptional: occurs at same time, more loops = 5’ end, detached = 3’ end
Intron Function: alternative splicing- one gene many polypeptides; exons not constant
exon shuffling- ^beneficial recombination/crossing over, change
protein domain w/no effect on sequence
Transcription
Translation
Purpose
DNA→mRNA
mRNA→polypeptide
Genetic Code
Triplets
Codons
Location
Nucleus
Ribosomes (Cytoplasm/RER)
Molecules
RNAP, RNA nucleotides
Ribosomes, tRNA, amino acids
Translation
RNA: rRNA/mRNA/tRNA, made by eukaryotic RNAP I,II,III in nucleus (euk, pro has 1)
● Primary Transcript: precursor to rmtRNA, will be spliced, has introns
● snRNA: small nuclear- plays structural/catalyst role in spliceosomes
● SRP RNA: part of signal recognition particle, recognise secretory pps in translation
● mRNA: transcribed from DNA, triplets = codons, codes for amino acid
● tRNA: carries amino acid to ribosome, has anticodon (complementary to mRNA)
2D cloverleaf, anticodon-bottom loop, 3D L-shape, amino acid attach site on 3’
Ribosome: ribonucleoprotein: double strand rRNA, alpha helix protein
● subunits: large: 60S, small: 40S, final: 80(Svedburg: speed of object sedimenting in centrifuge)
● binding sites: 1 mRNA btwn subunits, 3 tRNA (Exit, Peptidyl-chain- Aminoacyl-next addition)
●
free→cytoplasmic proteins→cytosol/mitochondria/chloroplast/nucleus/peroxisome
○
●
water soluble, folded by chaperonins, starts all translation
bound→secretory proteins→plasma membrane/secreted by exocytosis/lysosome
○
nascent protein will reveal a signal peptide (20 amino acids at N-terminus)
→signal recognition particle halts translation, binds to SP, brings translation
complex to the signal recognition particle receptor on ER membrane
→polypeptide put in translocon (like channel protein, threads pp in ER lumen)
→signal peptidase cuts off signal protein (not part of final product), released
Initiation Steps
Prokaryote
Eukaryote
Ribosome binds to mRNA
Shine Dalgarno sequence
5’ cap
Ribosome locates Start Site
(small subunit moves along
mRNA until reaching AUG)
Initiation Factors
-help to find start codon
Kozak Sequence
-help to find start codon
Initiator tRNA binds
w/start codon @P site
formyl-methionine amino acid
-has an aldehyde/=O
methionine amino acid
-has an amine
Large Subunit Binds
-requires energy, end
-requires energy, end
Elongation: (polymerization)
1) Codon Recognition: aatRNA→A site, H bonds formed btwn codon+anticodon
2) Peptide Bond Forms: ribosome catalyses bond btwn P-site to A-site amino, involves
the carboxyl at the end of pp chain→chain increases, add to A-site amino
3) Translocation: ribosome shifts over 1 codon A→P, + P→E, empty A-site ready
→1+3 require energy, translocation is unidirectional: 5’ to 3’, 1 codon, 3 nucleotide
Termination: STOP codon (release factor) binds to A site (no aatRNA for STOP)
Release Factor: adds water instead of amino acid, hydrolysis btwn tRNA and PP
Translation Complex Disassembles
Golgi body- where post-translational modifications occur
● Addition of sugars, lipids, phosphate groups
● Removal/Cleavage of some amino acids/whole pp chains
● Polymerization: 2+ polypeptides join to form protein (hemogoblin)
● Folding: (ex insulin- connecting sequence+leader removed after folding)
Polyribosomes: when 1 mRNA has 1+ ribosome, (multiple copies simultaneously)
Mutations
Genetic Code: universal: all living things use the same codon code for same amino acid
redundant: (64 codons, 45 tRNA molecules, 20 amino acids)
non-ambiguous: each codon only signifies 1 amino acid
20 amino acids and a STOP codon; start codon = Met; stop=/=amino acid
Reading frame: triplet grouping (codons) of a genetic message
Wobble Hypothesis: base pairing rules are flexible in the third base of the codon and its
corresponding tRNA anticodon (less amino than codon)
Mutation: change in genetic material, disorder/disease = harmful & passed on
Spontaneous: error w/genetic machinery in DNA replication or enzymes
Induced: exposure to mutagenic agents (mutagens)
● Physical: radiation, UV light, x-ray | Chemical: base analogues: similar to DNA
base, pairs incorrectly, distorts DNA Helix, change base properties
Effect of Mutation: RNA Codon, Amino Acid sequence, Protein Function
Codons
● Point Mutation- Substitution: one nucleotide is replaced with another
● Frameshift- Insertion & Deletion: loss/addition of 1+ nucleotide pairs
● No Frameshift- # of nucleotides added/lost is a multiple of 3: extra/missing amino
PolyPeptides
● Missense- altered codon codes for diff amino, may/may not have effect on protein
○
ex. Sickle Cell, A→T, glutamine→valine, negative
○
○
ex. antibiotic resistance/back mutation (restores original sequence), positive
ex. sometimes change in amino acid doesn’t change function, neutral
●
Nonsense- codon→stop codon, truncated protein, digested by cell, lethal 2 embryos
●
Silent- altered code for same amino w/no effect on protein; neutral; no amino diff
Mutation
Point Mutation
Frameshift
Missense
Nonsense
Silent
Yes
Yes
Yes
Yes, extensive
Yes
No
No frameshift
Yes, +/- amino acid
Yes
No
Gene Expression- amt of products formed, controlled at various levels, frequency of
transcription, regulatory proteins, effective binding of RNAP, splicing, transport channels,
protect/degrade mRNA, ribonuclease #, protein synthesis speed, post-transmodifications
Eukaryote: 1 gene 1 protein; splicing for variation; promoter controls 1 gene
Prokaryote: related genes in tandem, 1 promo can control more than 1 gene (operon)
1) Transcription: affects if RNAP can bind&transcribe, affects # of enzymes long-term
● Genes that are actively being transcribed are ON
● Genes that are not actively being transcribed are OFF
Types of Expression
Definition
Type
Constitutive
always ON
Housekeeping/Regulatory
Inducible
OFF, turned ON as needed
Structural, Catabolic
Repressible
ON, turned OFF as needed
Structural, Anabolic
Anabolic: repressible, usually on, produces essential nutrients
● nutrient production stopped only if in the environment
Catabolic: inducible, usually off, breaks down complex molecules
● waste of energy to make enzymes that break down substance when not present
2) Protein Activity: alters protein/enzyme function, short-term, quick, molecular
Negative Gene Regulation
Operon: group of genes that share a promoter
Regulatory Gene- makes regulatory protein, before operon, constitutive
Regulatory Protein: allosteric, binds to operator and blocks RNAP
Promoter- DNA region where RNAP binds, acts as ON/OFF switch
Operator- controls RNAP access, can activate/repress transcription
Structural Genes- to be transcribed by RNAP
Repressible: regulatory gene/repressor made in inactive form, activated by corepressor
trp Operon: produces tryptophan
● 5 genes for 5 polypeptides for 3 enzymes for trp synthesis
● trpR- regulatory gene/repressor constitutively expressed as inactive
○
trp binds to trpR, makes it active, binds to operon→ off; corepressor
○ negative feedback/feedback inhibition
Inducible: regulatory gene/repressor made active, inactivated by inducer (catabolic)
lac Operon: breaks down lactose
● lacZ- B-galactosidase: hydrolyzes lactose into glucose and galactose
● lacY- Permease: transports lactose into cell
● lacA- Transacetylase: adds acetyl group to galactose (unclear significance)
● LacI- regulatory gene/repressor, constitutively expressed as active
○ allolactose binds to LacI, inactivates, off of operon, turns on; inducer
● Positive Gene Regulation: cAMP on lac turns on production of enzyme
3) Eukaryotic Chromosome Structure: unwound affects reading ability of info, structural
● 2 arms, divided by centromere; p = petit, q = long arm
● Centromere: made of repetitive sequences
● Histone: proteins w/positive R-groups that bind w/DNA’s neg phosphate groups
○ Core: H2A, H2B, H3, H4 Linker: H1 (5 types total)
Four Levels of Packing: like protein
● Nucleosome: 8 core histones (2 of each) w/DNA wrapped twice around each
○ 10 nm diameter, beads-on-a-string, H1 attached to DNA near nucleosome
○ stays intact whole cell cycle
● Solenoid/Chromatin: H1 histones aggregate, stacking to form chromatin fibre
○ 30 nm diameter, supercoiling begins!
● Looped Domain: chromatin forms loops-attach to nonhistone proteins:form scaffold
○ 300 nm diameter
● Metaphase Chromosome: looped domain further coil to compact chromatin, which
results in the metaphase chromosome; called that bc it’s best seen in metaphase
Supercoiling: controls which genes are expressed
● transcription occurs if chromosome region is uncoiled, diff levels affects transcript
● Mitosis: inactive, most condensed
● Interphase: less condensed, scaffold less defined (attached to nuclear envelope)
chromosome occupies restricted area, most maintain solenoid+looped domain
Euchromatin: loosely packed chromatin area, active transcription (light stain)
Heterochromatin: densely packed region on chromatin, inactivated (dark stain)
Chemical Chromatin Modifications:
● Methylation: attachment of CH3 groups to DNA base, usually cytosine
○ occurs after S phase/replication, normally on unexpressed regions
○ suppresses expression, removal turns gene ON (neg gene reg)
● Histone Acetylation: attachment of COCH3 to histones, changes shape
○ loosens grip on DNA, activates expression (pos gene reg)
○ if removed (deacetylation), gene expression is suppressed
Biotechnology- manipulation of biological organisms, usually w/DNA
Isolating- disrupt membrane (detergent), precipitate w/ethanol, take/store DNA precipitate
Amplifying in Vitro- polymerase chain reaction, kary mullis Purpose: increase amt of DNA
Steps
Natural
PCR
-helicase unwinds (starts at ori)
-uses heat (denaturation 95°C)
Priming
-RNA primer
-Primase
-2 DNA primer
-Annealing temp (50-65°C)
Elongation
-Nucleotides
-DNAP
-Nucleotides
-Taq polymerase (72°C)
Termination
-End of Chromosome
-Meet another replication bubble
-End of DNA template
-Change in Temp
Unwinding
Target Sequence: appears after 3rd cycle
Primers: complementary to each end of target region of DNA, 20-30 nucleotides, 3’OH
Taq Polymerase: from thermoacidophile (thermus aquaticus) in hot springs, heat stable
● before Taq: PCR required 3 waterbaths, and addition of new DNAP at each step
○ Thermal Cycler; plate that heats/cools, takes 1-2 hours to complete
After 30 cycles, more than 1 billion copies are made
Amplifying in Vivo- use of bacterial cells
Transformation: alteration of bacterial genotype; uptake of foreign (often naked) DNA
● naked: DNA not inside a cell; therefore donor can be dead or nonexistent
Methods of Transformation
● Natural: some have surface protein-recognize/transport closely related DNA
● Artificial: may occur if cell wall is made permeable (2 methods)
○ Chemical: Cold CaCl2 followed by heat-shocking
○ Electroporation: shocked w/electric current to create holes
System
Vitro
Vivo
Definition
out of natural environment
inside natural/cellular environment
DNA Amplification
PCR
Transformed bacterial cell w/DNA
Advantage of
System
DNA can be partially
degraded and still be amplified
few errors in replication bc
proofreading (PCR has repeat
limitations)
Gene Cloning
1. Form recombinant DNA (genes from 2 diff sources combined)
DNA cut w/same restriction can be ligated together; (complementary sticky ends)
a. Gene of interest is put into a cloning vector (bacterial plasmid)
plasmid: few genes, self-replicating, can incorporate into chromosome
not req for life, resistance under stress, ^genetic variation/survival
R(esistence)Plasmid: resist antibiotics, carries sex pili gene
F(ertility) Plasmid: genetic recombination, encodes sex pili
Sex Pili: cytoplasmic bridge for bacterial gene transfer/conjugation
F+m→F-f, -/female bacteria becomes +/male upon receiving F+ plasmid
→Only 1 strand of plasmid is transferred; complimentary synthesized
episome: genetic element- either as plasmid or part of bac chromosome
Parts of a Cloning Vector
1. Ori: allows plasmid to replicate in host cell
2. ampR: resistance against ampicillin, if cell not resistant (no CV), it dies
3. LacZ: β-galactosidase will change clear substrate (X-gal) blue
a. recombinant put btwn lacZ/promoter, if blue in X-gal, no recomb
4. Cloning site: where gene of interest is inserted/ligated
a. has upstream promoter→ is where transcription will occur
b. DNA ligase seals gene of interest w/plasmid
2. Transformation: gene of interest will replicate w/the cell
a. bacteria grown in liquid medium flasks, incubated at optimal growing temp
3. Selection: identify bacteria w/gene of interest (no vector/vector no gene/vector w/gene)
a. Plating: putting sample into medium w/antibiotics and X-gal
i.
select for clones w/vector/proper transformation; antibiotic (ampicillin)
ii.
select for clones w/vector+GOI/proper ligation; X-Gal (blue=wrong)
Medium Contents
No Vector
Cloning Vector
Recombinant DNA
Amp
no growth
white
white
X-Gal
white
blue
white
no growth
blue
white
Amp+X-Gal
st
Flavr Savr Tomatoes: 1 genetic-mod, suppressed ripening gene w/reverse orientation
Bt Plants: Bt is a pesticide; is cloned into plants so they resist pests
Cutting DNA- Endonuclease: cut in middle of sequence; breaks phosphodiester bonds
● Restriction Enzyme: recognise short nucleotides in foreign DNA
○ protection against invading DNA of other organisms (phages/bacteria)
○ cut covalent phosphodiester bonds of both DNA strands, make it harmless
○ Naming: BamHV- Bacillus amyloliquefaciens, strain H, 5th endonuclease
● Restriction Site: one per restriction enzyme, which will cut at a particular bond
○ 4-8 bp, palindromic (same sequence on complementary in opposite order)
○ results in blunt or sticky ends (w/5’ or 3’ overhang)
Visualizing/Gel Electrophoresis: can also be done on protein
● Nucleic Acids are separated by size; moved through gel medium w/electric current
● 1) restriction enzymes cleave DNA into smaller segments of various sizes
●
●
2) load segments into walls of porous gel, float in buffer solution btwn 2 electrodes
3) electric current passes through, DNA moves towards the positive electrode
○ long: caught up in web of polymers, slow short: goes farther, faster
Materials:
● Gel: liquid solution set in mould, solidifies; comb @one end; create loading wells
●
●
●
Gel Medium Type
Agarose
Polyacrylamide
Source
Seaweed Extract
Artificial Polymer
Resolving Power
(+conc=higher res)
Lower Resolution
Higher Resolution
Separation
Nucleic Acid
Nucleic Acid Protein
Liquid Buffer w/ions: medium for electric current, prevents overheating/drying
Coloured Dye: track distance moved, add density to DNA- sink to bottom of wells
Ethidium Bromide: visualization, binds to DNA, carcinogenic, glows under UV light
DNA Fingerprinting- Jefferys, (1984) Identifies person based on genetic code
● First criminal case: Colin Pitchfork, Arrested for rape/murder by DNA fingerprinting
○
Richard Buckland was prime suspect → proven innocent
Human Genome: 20-30 thousand genes, 98% is non-coding, 2% for protein/RNA
Tandemly Repetitive DNA: most non-coding, harmless to fingerprint; (VNTRs)
● Short identical sequences repeated in tandem/series
●
Subcategory: short tandem repeats (STRs) → 4 bases
●
Polymorphic: many forms, varies in length based on repeats, #varies per person
○ More than 2 standard alleles (ie heterozygous vs homozygous)
Fragile X syndrome: CGG repeats on X chromosome, May cause disabilities/autism
○ Normal: repeat 30x on 5’ UTR Fragile X: repeat 100x
Huntington’s disease: CAG repeats: <35: - 36-39: -/+ >39: +, neurodegenerative
DNA fingerprinting method/STR analysis Use PCR
●
●
●
STR Polymorphism:
● 2 copies per person: different lengths (heterozygous) or the same length (homozygous)
● STR loci are polymorphic but ratio of allelic frequency:population is small
○ Alleles shared by 5-20% of people; NA, 13 loci + AMEL (sex) looked at
Sequencing: find genome, organism’s complete set of DNA; human- 3 billion bp
Human Genome Project: international research project (98-03), map human genome
● in universities, parallel project by Celera Genomics private company
● shotgun sequencing: multiple genome copies in small fragments sequenced, assembled
w/computer matching overlapping sections (con: repeat sequence length)
Dideoxy Termination Sequencing: by Sanger (also found insulin structure)
● Dideoxyribonucleotides: 2’ + 3’ OH missing; terminates elongation
● each reaction vessel has 1 of 4 ddNTPs; dNTP: 15% ddNTP: 10% of 25%
●
separated using gel electrophoresis in 4 lanes; sequence read 5’→3’ (bottom→top)
Modern Sequencing: simplified Sanger
● ddNTPS are fluorescently dyed diff colours, can be put in 1 test tube and 1 lane
● computers read the colour wavelengths
Thermochemistry-study of energy transformation
Where does our kinetic energy come from? Potential energy in food (chemical respiration)
Where does chemical energy in food come from? light energy by plants (photosynthesis)
ATP Hydrolysis: Hydrolysis releases the end phosphate group: ATP → ADP + Pi
●
●
DG = -7.3 kcal/mol under standard conditions ,DG = -13 kcal/mol in a cell
Phosphate Bonds: called high-energy bonds, actually fairly weak covalent bonds
○
●
Each phosphate group is negative, repulsion→instability of ATP phosphate
hydrolysis yields energy→products are more stable
ATP Coupling: Energy from hydrolysis of ATP is coupled to endergonic processes
Regenerating ATP: regenerated by adding phosphate group to ADP, entire pool recycled in 1
minute, 10 million ATP consumed/regenerated per second, Endergonic: DG=7.3
● Energy for renewal comes from catabolic processes in cell
Redox with NAD+/NADH: NAD+: reduced, oxidizing agent, + e- →NADH (electron carrier)
●
●
●
●
●
Dehydrogenase enzyme removes H2 (2 electrons/protons) from substrate
2 electrons and 1 H+ stay on NADH leaving 1 H+
Each NADH molecule represents stored energy that can make ATP
Electrons in NADH fall down energy gradient to oxygen, ΔG= -53 kcal/mol (ETC)
In cellular respiration: glucose=oxidized, oxygen=reduced
Cellular Respiration- stored bond energy organic fuel→ATP,
●
glucose + oxygen → carbon dioxide + water + energy
●
C6H12O6 + 6 O2 → 6 CO2 + 6 H2O, GOALS v + collect ATP
○
●
(ΔG= -686 kcal/mol) exer
break 6C glucose down, release 6 CO2,glucose e-s→O2, w/ H+ → 6 H2O
X ADP + X P → X ATP
X= 36 or 38
Stored Energy in Human Body
Sources of Energy
Glycogen (carbs) (plants: starch)
Carbohydrates; most usable (glucose)
Fats (Lipids)
Lipids; energy after carbs
Muscle Tissue (Protein)
Protein; cells break down self at last resort
Enzyme
Reaction
Description
Kinase
Phosphorylation
Phosphate group removed to another molecule
Dehydrogenase
Redox
Electron transfer, usually to NAD+ → NADH and FAD+
Decarboxylase
Decarboxylation
Removal of carbon, usually as CO2. CO2=waste product
Isomerase
Isomerization
Produces isomers, also called mutase
Lyase
Cleavage
splitting/removal of part of a molecule
Synthase
Synthesis
formation of molecule, from 2+ molecules
Hydrase
Hydration
Addition of water to a molecule
Glycolysis- splitting of sugar in cytoplasm (glucose6C→3Cpyruvate)
Investment
Step 1: carbon 6 phosphorylated w/ATP, prevents glucose from leaving the cell
● kinase, energy absorbed
Step 2: atoms of molecule are rearranged; fructose
● isomerase, energy equilibrium
Step 3: carbon 1 phosphorylated, causes fructose to be energetically unstable
● kinase, energy absorbed
Step 4: unstable fructose is split into two molecules; DHAP, G3P
● lyase (cleavage), energy equilibrium
● dihydroxyacetone + glyceraldehyde-3-phosphate; G3P continues
Step 5: DHAP → G3P (isomerized)
● isomerase, equilibrium
Payoff. x2, below is for 1 G3P
Step 6: NADH (energy molecule) is created
● dehydrogenase (redox and phosphorylation) energy released
● electrons from G3P transferred to the oxidizing agent, NAD+, to form NADH
● uses energy from exergonic transfer above to add phosphate from cytosol to the
oxidized G3P to form 1,3-Bisphosphoglycerate
Step 7: ADP substrate-level phosphorylation to create ATP
● kinase, energy released
●
ADP picks up phosphate from 1,3-Bisphosphoglycerate → ATP
Step 8: phosphate moved from carbon 3 to carbon 2
● isomerase, equilibrium
Step 9: water removed to set up next reaction
● lyase (dehydration) energy released
Step 10: ADP phosphorylation to ATP; pyruvate formed
● kinase, energy released
Summary: glucose → +2 pyruvate, +2 ATP (2 used 4 made), 2 NADH
Pyruvate Juncture: Krebs + ETC if O2 present, fermentation (anaerobic) otherwise
Anaerobic Cellular Respiration: pyruvate undergoes fermentation if no O2 present
● only glycolysis will make ATP, cells w/no mitochondria only use this
● ATP production is the result of glycolysis coupled w/fermentation
● point is to replenish NAD+ for glycolysis reuse
○ important: NAD+ is necessary for G3P→pyruvate steps/setup for ATP prod
Alcohol Fermentation- in yeast, organisms w/no mitochondria
●
pyruvate → acetaldehyde (2C): decarboxylase, CO2 lost
●
acetaldehyde → ethanol (2C): alcohol dehydrogenase
●
NADH→NAD+ | Ethanol can’t become pyruvate even if O2 is present
○
(bread production)
(brewing/wine making)
2 pyruvate→ 2 acetaldehyde→ 2 ethanol (+2 NAD+, -2CO2)
Lactic Acid Fermentation- in humans + some fungi/bacteria, dairy, Lactate is 3C
● Lactate dehydrogenase converts pyruvate into lactic acid as waste product
○ buildup causes muscle pain, carried to liver, turned into pyruvate
○ rubbing muscles lowers pain bc gets lactate out faster
● replenishes NAD+ by removing H+, for each pyruvate, 2 for glucose
●
2 pyruvate → 2 lactic acid (+2 NAD+)
Aerobic Cellular Respiration:
Pyruvate Oxidation- brings pyruvate into mitochondria, makes it small enough to enter
●
Step 1: CO2 removed from pyruvate→2C molecule (decarboxylase)
●
Step 2: H+ added to NAD+ → NADH (dehydrogenase, redox)
●
Step 3: CoA-SH+pyruvate→Acetyl CoA (synthase, CoA: thiol- active functional)
●
2 pyruvate→2 acetyl-CoA (+2 NADH, -2 CO2, energy released)
Krebs Cycle- makes high energy molecules (NADH, FADH2, ATP) citric/tricarboxylic acid cycle
● -2 CO2, +3 NADH, +1 FADH2, +1 ATP (substrate-level phosphorylation) x2 per glucose
Step 1: 2C + 4C, recycle/removal of CoA-SH
● synthase, energy absorbed
Step 2: H2O helps rearrange atoms
● isomerase, equilibrium
Step 3: 6C→5C, CO2 and NADH are synthesized
●
decarboxylase+dehydrogenase (redox+decarboxylation), energy released
Step 4: 5C→4C, CO2 and NADH are synthesized, CoA is added
● decarboxylase/dehydrogenase (redox/decarboxylation/synthesis), energy released
Step 5: ADP phosphorylation to ATP, CoA recycled/released
● kinase + lyase (substrate level phosphorylation, cleavage) energy released
Step 6: FADH2 created (FAD+ -oxidized, FADH2 reduced|flavin adenine dinucleotide)
● dehydrogenase, energy released
Step 7: rearranging the molecule for the next reaction
● hydrase, energy absorbed
Step 8: NADH formation & recreation of 4C for step 1
● dehydrogenase (redox), energy released
Summary: 2+4, rearrange, 6→5, 5→4, ATP, FADH2, rearrange, NADH
Electron Shuttle move NADH produced in glycolysis to ETC in mitochondria
● indirect bc mitochondria is non-permeable to NADH
● outer/inner mitochondrial membrane (OMM/IMM)
Glycerol Phosphate Shuttle- in brain/skeletal muscle tissue, 36 ATP instead of 38
Electrons from NADH shuttled into mitochondria onto FAD resulting in FADH2 in the matrix
1. e- transfer from NADH to DHAP→G3P, dehydrogenase, redox; opp glycolysis step 6
2. porins on the OMM allow G3P entry to IMM
3. dehydrogenase on IMM removes G3P electrons to FAD+, becomes FADH2
Malate-Aspartate Shuttle- liver, kidney, heart, [1-3 entry, 4-6 recycle]
e-s from NADH shuttled into mitochondria and onto NAD+ → NADH in the matrix
1. transfer e-s from NADH to oxaloacetate→malate, dehydrogenase; opp krebs step 8
2. transporters on OMM and IMM allow malate to enter the matrix
3. dehydrogenase in matrix transfers e-s from malate to NAD+ → NADH
4. OAA+glutamate→aspartate + aKG, catalyzed by transaminase (aminotransferase)
a. glutamate+aspartate are amino acids, switch ketone w/amino group
5. transporters on OMM and IMM allow aspartate to exit the mitochondria
6. reverse transaminase rxn in cytoplasm: aspartate + aKG→OAA + glutamate
Oxidative Phosphorylation: Oxidation (ETC) with phosphorylation (ATP synthesis)
Types of ATP Synthesis
1. Substrate-level phosphorylation: direct ATP from ADP + P; glycolysis and Kreb’s
2. Oxidative phosphorylation: indirect ATP through O2 redox reactions; ETC
Electron Transport Chain (ETC)- all redox
●
Energy in NADH and FADH2 electrons → drive H+ against c. gradient
●
Electrons fall to oxygen (final electron acceptor, high EN)
○
●
Oxygen + electrons + free hydrogens → water (final product)
○ Oxygen drives redox reactions; lack thereof prevents process
Made of protein electron carrier molecules embedded in IMM except ubiquinone/Q
ETC Thermodynamics: each electron transfer step is energetically favourable
● Each carrier in the chain has a higher electronegativity than the carrier before it
● Electrons from NADH and FADH2 lose energy (pulled downhill)
ETC Components
Complex I: 2 e-s from NADH are transferred into complex, pumps protons across IMM
Q: e- transferred from complex I and II→Q, lipid soluble, can move within bilayer (mobile)
Complex III: e-s transferred from Q into complex, pumps protons across IMM
Cytochrome C: e-s transferred from III to cyt c, mobile, peripheral protein in IM space
Complex IV: e- transferred from cyt c→IV, protons pumped across IMM
O2: final electron acceptor in ETC, enough e- pass through ETC to produce H2O
Complex II: 2 e-s from FADH2 transferred to II via Q, no protons pumped
ETC Summary: NADH e- → O2, three proton pumps activated; FADH2 e- transferred to O2, two
proton pumps activated; electrochemical proton gradient formed across IMM
Chemiosmosis (proton motive force): facilitated diffusion of proton down c. gradient
●
Passive movement of protons → ATP through enzyme complex V ATP synthase
○
ATP is produced as protons flow through
Chemiosmosis Summary: 1 NADH=3 ATP, 1 FADH2=2 ATP, ETC is coupled with ATP
synthesis, ATP synthesis (chemiosmosis) depends on ETC
ATP Conversion
ATP
NADH
FADH2
CO2
Glycolysis
2
2
0
0
Pyruvate Oxidation
0
2
0
2
Kreb’s
2
6
2
4
Subtotal
4
10
2
6
ETC Conversion
4
30
4
N/A
Catabolism of various molecules
Proteins (amino acids): to pyruvate, acetyl-CoA or Kreb’s cycle, ammonia byproduct
Fatty acids: acetyl-CoA
Glycerol: G3P
Photosynthesis- Light energy converts inorganic compounds → organic fuel
●
Carbon dioxide + water → sugar + oxygen; energy in bonds
● Photosynthesis and cellular respiration: complementary; process has diff steps
Variants
Photoautotroph: plants (photosynthetic)
Photoheterotroph: specialized bacteria
Chemoautotroph: archaebacteria
Chemoheterotroph: animals
Nature of light: radio→gamma, long→short, red→purple
●
Form of energy w/different wavelengths, shorter wave→greater energy per photon
●
Certain wavelengths seen by us → visible spectrum: drives photosynthesis
●
Pigment: groups of light absorbing molecules, colour= wavelengths being reflected
○ Chlorophyll: absorbs blue/red, reflects green
○ Carotenoids: absorb green/blue, reflect red/orange
○
In autumn chlorophyll breaks down first → carotenoid colours show
Light reactions: photoexcitation, electron transport, photophosphorylation/chemiosmosis
“Photo”: Light dependent, in thylakoid, energy fixing, light energy → ATP/NADPH
“Synthesis”: light-independent, carbon fixing, calvin cycle, ATP→inorg to organic fuel
●
Input: water, light photons; output: oxygen, NADPH, ATP
Thylakoid Proteins
PSII (P680): absorbs light, e- captured by primary electron acceptor, oxidizing agent
Plastoquinone (Pq): moves e- captured by primary electron acceptor to ETC’s cyt complex
Cytochrome Complex: pump protons against cgradient, stroma→lumen, across membrane
Plastocyanin (Pc): e- transferred from cyt complex, on lumen side of membrane
PSI (P700): e- excited by light, captured by primary electron acceptor, P700 oxidized
Pc transfers e-s to P700 to replace lost e-s
Ferredoxin (Fd): has iron, on stromal side of thylakoid membrane, moves e-s to reductase
NADP+ Reductase: NADP+ reduced to NADPH, NADP+=final e- receptor
NAD+ vs NADP+: latter has phosphate group, will provide reducing power for synthesis
of sugar in the Calvin cycle, vs decomposition of sugar in Krebs
ATP Synthase: protons pumped in lumen go in ATP synthase w/same method in cell resp
ATP produced in stroma
Photoexcitation: absorption of light photons → splits water, releases electrons
●
atoms absorb sun energy, electrons gain energy; “excited”
○ will return to ground state if not transferred to electron acceptor
Photosystem: 100s of clustered pigments in transmembrane proteins of thylakoid
● Reaction Centre: 1 chlorophyll next to primary electron acceptor
○ Photosystem I: Reaction‐ centre chlorophyll is P700
○ Photosystem II: Reaction‐ centre chlorophyll is P680 (thylakoid)
○ #=optimal wavelength for absorption; diff, interact with diff proteins in photosystem
● light excites e- on reaction chlorophyll (centre chlorophyll a)
● primary electron acceptor traps high energy e- before it returns to ground state
●
P680 misses an e- and takes e-s from lumen/water, H2O→ H + O2
Photophosphorylation (chemiosmosis): ATP synthesis
● ETC provides energy for photosystems to pump H+ from stroma to lumen
●
Electrochemical proton gradient provides proton motive force needed to make ATP
Types of Electron Transport Mechanisms
Non‐ cyclic electron flow (Z‐ Scheme)
● Photoexcitation: H2O is split in end, O2 is released, H+ ions released in lumen
● ETC creates electrochemical proton gradient; H+ in lumen via cytochrome complex
● Photophosphorylation: light‐ dependent formation of ATP by chemiosmosis
● NADP+ is final electron acceptor and produces NADPH w/reductase
Cyclic electron flow- no NADPH made, only involves PSI P700
● ferredoxin returns e-s to cytochrome complex
● protons pumped into lumen to produce more ATP through chemiosmosis
● increases ATP production, no effect on NADPH production
○ In Calvin cycle, more ATP is used than NADPH
○ When ATP is low, NADPH will accumulate bc calvin cycle slows
○ Rise in NADPH levels stimulate a temporary shift to cyclic electron flow
Compare Electron Transport Chains
Cellular Respiration
Photosynthesis
Mitochondria
Chloroplast
H+ Pumps
Complex I, III, IV
Cytochrome Complex
[H+] high
Matrix
Thylakoid Lumen
Intermembrane
Thylakoid Membrane
Intermembrane Space
Stroma
Cyt C (IM space)
Fd (stroma side) Pc (lumen side)
Location
H+ pumped across
[H+] low
Peripheral Proteins
Calvin Cycle (Dark): Carbon fixation, Reduction, Regeneration
Carbon Fixation: CO2 (1C)+RuBP (5C)=short lived 6C intermediate, split in 2 (3PGA/PGA/3PG)
● rubisco (synthase), energy absorbed, 3 times per cycle; therefore 6 3C are made
Reduction: 6 G3P created
●
6ATP→ 6ADP, phosphorylates each 3C; kinase, energy absorbed
● NADPH used to synthesize G3P; dehydrogenase (redox), energy absorbed
Regeneration: 1 G3P exits, 5 continue cycle to regenerate start
●
G3P + 3 P from 3 ATP→ 3 ADP, resynthesized to 3 1,5-RuBP,
○
●
●
5 x 3C (G3P) → 3 x 5C (RuBP); 15 carbons in total
3 ATPs = 3 phosphates = 3 RuBP made
Synthesis reaction (synthase), absorbs energy
Rubisco: large, slow, plants need lots=½ protein in leaf, most abundant on earth
● Carboxylase: binds CO2 yields 2x PGA
●
●
●
●
●
Oxygenase: binds O2 yields 1x PGA and PG
Evolutionary Baggage: developed when there was less O2 than CO2 in air
Rubisco’s inability to exclude O2 had little effect on photosynthesis at the time
Now it is responsible for poor crop yields
Evolutionary Efficiency: atmospheric O2 is 500x CO2, rubisco fixes 4 : 2 CO2 : O2
Phosphoglycolate (PG): waste of carbon, cannot be converted directly into sugars
● Phosphorespiration, energy-expensive, required to retrieve carbon from PG
○ Photo: in light (no calvin) | Respiration: uses O2, no ATP/organic fuel
○ dangerous byproduct H2O2 in peroxisome, waste energy + reducing power
Adaptations to Limitations -photorespiration limitation (C3), adaptation to heat (C4, CAM)
C3 Plants: first organic product of its carbon fixation phase is a C3 compound
● Stomata open during day, closed at night/in hot conditions, which are harmful
● Closed stomata = decreased CO2, increased O2, no change to light reactions, slow/no
Calvin, no glucose produced, rubisco binds to O2
C4 Plants: alternate carbon fixation, produces 4C compound not 3C, (sugar cane, corn)
● Spatial/structural separation:light/O2 in palisade mesophyll, rubisco in bundle-sheath
● Specialized bundle-sheath cells beside mesophyll around vascular bundle
● CO2 is pumped by mesophyll cells into bundle-sheath cells for Calvin Cycle; CO2 is 10120 x higher than normal in bundle-sheath so rubisco binds
● PEP carboxylase can fix carbon in high O2 and lower CO2
○
1) CO2 + PEP→OAA→malate
○ 2) 4C exported to bundle sheath, releases CO2 + 3C pyruvate
○ 3a) CO2 assimilated into Calvin Cycle by rubisco
○ 3b) pyruvate returns to mesophyll to be converted into PEP (3C)
have fun at slide 38 of calvin LEL
CAM Plants: Crassulacean acid metabolism, succulent (water storing) ie pineapple/cactus
● Temporal (behavioural) separation
● Calvin cycle doesn’t stop in heat like C3
● Initial carbon fixation separated temporally
Daytime: hot, stomata closed, conserves water, no CO2 uptake
●
Light reactions → ATP + NADPH + O2
●
CO2 in malic acid from the night is released to run Calvin cycle
○
Malate (4C) → pyruvate (3C) + CO2
● Light reactions also occurring so the ATP & NADPH help run Calvin cycle
● Calvin cycle with energy from light reaction and CO2 from night storage
Nighttime: cooler, stomata open, CO2 enters
●
Enzyme PEP carboxylase (CO2 + PEP (3C) → OAA (4C); high CO2 affinity)
○
Converted to organic acid (malate) → stored in mesophyll vacuoles
● CO2 incorporation into organic acids, stored in vacuole
Look at slide 46 diagrams
Factors affecting photosynthesis: Light Intensity, CO2 concentration, Temperature
Homeostasis- “dynamic equilibrium” requires energy
Positive Feedback positive cycle ex. progesterone in pregnancy
Thermoregulation- regulation of internal body temp within acceptable range
Ectotherm
Endotherm
Metabolic Rate
Low
High
Heat Generation
Too little to warm body
Enough to keep body warm
Internal Body Temp
Determined by environment
Stable
Example Organisms
fish, reptiles, amphibians
mammals, birds
Thermoregulator
IF behavioral adaptation
Yes
Thermoregulator
Advantage
Disadvantage
High levels of aerobic metabolism
● perform vigorous activity (flight)
Enable terrestrial living
● land temp- more variable than aquatic
Energetically expensive (for 20oC)
● humans: 1300-1800 kcal/day
● alligator: 60kcal/day
Need to consume more food
Adaptations
Physical: Insulation: hair, fur, feathers, fat under skin
Behavioral:
● Gross Movement: walking jumping running etc.
● Huddling: decrease surface area & heat loss
● Relocating: finding shade/sun, migration
● Torpor: low metabolic activity; during environmental extremes, conserves energy
● Hibernation: long-term torpor; survive long low temp & little energy, body tempv
● Estivation: summer torpor; survive long high temp or low water, ex. lung fish
Circulatory: Countercurrent Heat Exchange: warm artery next to cold veins, making vein
blood returning back to the heart almost as warm as the body core
Physiological Changes HELPM
● Rate of Heat Exchange
○ Vasoconstriction: decrease superficial blood vessel diameter, blood flow to
surface (cools skin), heat loss from body, redirected to torso/organs
○
Vasodilation: increase diameter of blood vessels near body surface, blood flow to
surface (warms skin), body heat → environment
○
○
●
extreme cold- frostbite to preserve organs; hypothermia- very low body temp
cryopreservation suspends life of dehydrated cells (2-8 cell egg, blood, tissue)
■ frozen wood frogs
Evaporative Heat Loss: water absorbs heat in evaporation; sweat removes heat
●
Rate of Heat Production: skeletal muscle contract→ shivering→ goosebumps
●
Rate of Metabolic Heat Production:
○
White Fat Cell: single large lipid vacuole, sugar→fat storage
○
Brown Fat Cell: multivacuole, lots of mitochondria, endotherms, in newborns
babies don’t shiver, mitochondria: sugar→ATP/heat, no insulin needed
■
Non-Shivering/Adaptive Thermogenesis = ^brown fat cells/activity
■
Hormones→mitochondria ^metabolism, produce heat instead of ATP
Brain: Body’s Thermostat
● Sensory receptor (input): thermoreceptors on skin sense temperature
● Integration: hypothalamus, contains neurons that respond to body temperature
● Effector (output): behavioral/physiological changes
Stimulus
Cold Response (slide 30)
Heat Stress Response
Blood Vessels (heat exc rate)
vasoconstriction
vasodilation
Sweat Glands (heat prod rate)
decrease sweat production
increase sweat/evap cooling
Skeletal Muscles (evap heat loss)
shivering
N/A
Osmoregulation- affect internal pH/metabolite concentration/waste management,
composition of internal body fluid/maintain cytoplasmic composition in cells/manages:
● Body’s water content (blood volume/pressure)
● Solute composition (body fluid composition, metabolite concentration, blood pH)
● Solute Movement btwn internal fluids/environment (excretion of metabolic waste)
Examples of Osmoregulators: Marine Iguana: special organ takes salt out of system→ iguana
spits salt out head Pacific salmon: in salt/fresh water, manages body water content
Fish osmoregulation: water via osmosis (skin/gills), salt via diffusion across gills
Saltwater Fish (Hyperosmotic) (slide 7):
● Increase water volume (counteract water loss)
○ excreting small volume of concentrated urine
○
●
drinking seawater→ remove salt via active transport
Remove excess salt (counteract salt gain)
○ active transport
Freshwater Fish (Hypoosmotic) (slide 8):
● Decrease water volume (counteract water gain)
○ excrete large volume of dilute urine
● Gain lost salt (counteract loss)
○ retain salt from foods/active uptake from surroundings
Human Osmoregulation:
Body Parts and Components:
1) Total water body (TWB): liquid inside body, none in lungs, urinary tract, esophagus
2) Intracellular fluid (ICF): liquids inside cells (cytosol)
3) Extracellular fluid (ECF): liquid inside body, outside cell
4) Plasma: liquid of bloodstream
5) Interstitial fluid (ISF): liquid inside body, bathing body cells
Transport Epithelium: epithelial cells, regulate solutes, alveoli, intestine, kidney tubules
controls movement of specific solutes in controlled amounts in a particular direction
● Apical membrane: faces lumen of a body cavity
● Basolateral (base & sides) membrane: facing the interstitial fluid
● Basement membrane: anchors basolateral membrane/supports epithelial layer
● Tight Junctions: impermeable barrier between internal cells and environment
○ Limit passage of material through space btwn cells (paracellular)
●
(Re)Absorption: transport material from outside→internal environment
●
Secretion: transport material from internal environment→outside
Polarized Epithelial Cells: transport across cell; membrane on one side has transport systems
that are different from the other side; thus epithelial cells are polarized
● Active transport solute molecules increase solute concentration in interstitial fluid
● Water flows from lumen, through cells, to the interstitial fluid; secondary
Metabolic Waste mostly nitrogenous,from breakdown of proteins and nucleic acids when used
for energy/converting carbs and fat, waste converts to urea/uric acid/ammonia
Ammonia: removal of amine from amino acid, soluble/toxic, diluted w/water
● aquatic species | (0.005 mg NH3 is lethal)
● Q: Why is it safe for fish to excrete ammonia?
Urea: product of ammonia + CO2, made in liver, requires energy, low toxic (100,000x less NH3)
reduces amount of water needed for excretion
● mammals, amphibians, some sharks/fish
Uric Acid: Breakdown of nucleic acids, insoluble (semi-solid/little water loss) non-toxic
● Birds: flight & weight, migration & water loss = worth high energy cost
● Reptiles: water retention = worth high energy cost
● Embryos store nitrogenous waste in egg, prevent diffusion/self-poisoning.
Waste
Ammonia
Urea
Uric Acid
Toxicity
High
Low
Non-Toxic
Solubility
High
Soluble
Insoluble
Synthesis
amino acid deamination
NH3+ CO2
breakdown nucleic acid
Organism
fish
mammals
birds/reptiles
Excretory System- Kidney→Ureter→Bladder→Urethra
Urinary Tract Infection: bacteria in urinary tract, blood, discharge, frequent urination
Kidney Stones: crystallized urine solutes, increase water consumption, surgery
Urine: salt, water, organic compounds (4x [blood]) fluid comes from ECF, Plasma, ISF
Excretion: 200mL signal brain|600mL involuntary release, approx. 2L of liquid/day
Mammalian Kidney: pair, 10 cm long, ducts/tubules→ carry urine, dense capillaries
●
●
Renal Cortex: outside Renal Medulla: middle Renal Pelvis: inner portion
The Nephron: functional unit (million per), blood vessels surround tubules/ducts
○ contains filtrate in tubules, filters blood, reabsorption, secretion, excretion
○
Filtration: glomerulus transport epithelium filters blood→bowman’s capsule
■
blood pressure forces fluid through
○
Secretion: blood→interstitial→filtrate, protein transporters solutes/toxins/waste
○
Reabsorption: filtrate → interstitial fluid → blood, uses protein transporters
■
retain bodily fluid without replenishing it
Blood Flow: Renal artery→Afferent arteriole→Glomerulus capillaries→Efferent arteriole→
Peritubular capillaries -OR- Vasa recta → Renal vein→ inferior vena cava
Filtrate: Bowman’s capsule→Proximal tubule→Loop of henle→Distal tubule→collecting duct→
renal pelvis, ureter, bladder urethra.
STEPS OF FILTRATION
Step 1: Bowman’s Capsule: (Surrounds Glomerulus)
● Active and Passive transport
●
Glomerulus → Bowman’s capsule (High blood pressure)
● Blood retains large molecules (cells), filters small molecules, nitrogenous waste
Step 2: Proximal Tubule
● Selective reabsorption into peritubular capillaries
○ Active transport - valuable nutrients/salt
○ Passive transport of water
● pH determined by HCO3 reabsorption, H+ and NH3 secretion
● Also secretes drugs&poison
Step 3: Loop of Henle - Descending limb
●
Transport epithelium permeable to water → impermeable to salt/small solutes
●
Reabsorption of water by osmosis
○ Interstitial fluid is hyperosmotic
○ Osmolarity of interstitial fluid becomes progressively greater from outer cortex to
inner medulla
Filtrate becomes more concentrated as it moves down into the medulla
●
Step 4: Loops of Henle - Ascending limb
● Transport epithelium is permeable to salt but not water
● Thin segment: NaCl passive transport: diffusion possible bc concentrated filtrate
● Thick segment: NaCl active transport
● Filtrate becomes more dilute as it moves up towards the cortex
Countercurrent Flow:
●
Flow of filtrate in Henle and flow of blood in vasa recta → opposite directions
● Less concentrate filtrate beside less concentrated blood (and vice versa)
● Contributes to establishing the osmotic gradient
● Increase the efficiency of reabsorption
Step 5: Distal Tubule
● Water reabsorption is passive and secondary
● Regulates [K+][NaCl] controls active transport of K+ secretion/NaCl reabsorption
● Contributes to pH regulation: secretion of H+, reabsorption of bicarbonate (HCO3-)
Step 6: Collecting Duct Collect from several nephrons, function: concentrate filtrate
● Different sections have different permeabilities, permeable to water throughout
● First half only permeable to water, no other solutes, filtrate becomes concentrated
○ Enables conservation of water
● Duct is permeable to NaCl only in outer medulla, regulates amount of NaCl in urine
○
●
●
Reabsorption of NaCl by active transport→further reabsorption of water
Duct is permeable to urea only in inner medulla
○ Urea diffuses out to interstitial fluid due to high urea concentration in filtrate
○ urea and urine that is absorbed is less than that was filtered into nephron
Contributes to hyperosmotic environment: drives reabsorption of water by osmosis
enables conservation of water, filtrate becomes increasingly concentrated
Solute
Proximal
Tubule
Loop of Henle
Distal Tubule
Collecting Duct
Water
R
R (desc)
R
R
NaCl
R
R (ascn)
R
R (outer medulla)
H+
S
S
HCO3-
R
R
Glucose
R
R
Amino Acids
R
R
Vitamin/Minerals
R
R
Urea/Uric Acid
S
S
R (inner medulla)
Regulation of the Excretory System: Endocrine System (hormones used for homeostasis)
●
●
●
ADH: antidiuretic hormone
RAAS: renin-angiotensin-aldosterone system
ANF: atrial natriuretic factor
Kidney’s Effect on Blood (all below are neg feedback, slide 13, 19
Osmolarity: [solute], contributes to osmotic pressure: force prevents osmosis into solution
●
●
high solute concentration→ dilute blood, retain & intake water: (slide 13)
○ caused by water loss (sweating, dehydration, diarrhea)
AntiDiuretic Hormone: antidiuretic = decrease urination/retain water
○ short peptide, made in hypothalamus, made in posterior pituitary gland
○ readily available instead of waiting for transcript/translation
○
Stimulus: ^blood osmolarity→ osmoreceptors→ pituitary→ ADH released
●
○ Target: distal tubule, collecting ducts
○ increase thirst: increase volume of water
○ increase epithelium water permeability: increase reabsorption of water
○ dilute blood/lower osmolarity = less frequent, more concentrated urine
Diuretics: coffee/alcohol, inhibit ADH, less reabsorption, increased urine
●
Diabetes Insipidus: deficient ADH→ kidneys cannot preserve water
○
○
dilute urine, frequent urination, excessive thirst
drink lots of water, take ADH medicine
Blood Pressure: pressure on blood vessels due to pumping, blood volume^=pressure^
●
low blood pressure/volume→ increase BP and volume, constrict area, retain water
○
●
●
caused by low salt diet/water loss (sweating, dehydration, diarrhea)
juxtaglomerular apparatus JGA, detects, beside glomerulus, near afferent, secrete renin
○ effects glomerulus the most; needs high BP for filtration
Renin-Angiotensin-Aldosterone System: stimulated by low BP, steroid
○
angiotensinogen (constitutive)→angiotensin II
■
●
constricts blood vessels, aldosterone→distal tubules
■ ^NaCl reabsorption in proximal, ^water simulator
■ Aldosterone: adrenal glands above kidney reabsorption, ^BP/volume
Atrial Natriuretic Factor: stimulated by high BP, peptide hormone from atria walls
inhibit NaCl reabsorption (angiotensinogen→angiotensin II)→ decrease water
reabsorption→decrease BP/volume | inhibit renin→reduce aldosterone
Hormone
ADH
RAAS
ANF
Stimulus
high osmolarity
low BP/volume
high BP/volume
Cause
water loss
water/blood loss, low salt diet
water retention, high salt
Effect
^reabsorption
^reabsorption, vasoconstriction
decreased reabsorption
ADH and RAAS are needed because they respond to different stimuli.
pH Balance: conversion of CO2 to other compounds help regulate blood pH
●
H2O + CO2 + H+⇔ H2CO3 (carbonic acid) ⇔ HCO3 (carbonate ion)
○
carbonic acid reabsorbed in proximal+distal tubule
Endocrine System-coordinates long-term responses using chemical signals
●
Nervous: Internal Senses→CNS→Autonomic Sympathetic/Parasympathetic
Hormones- chem signals carried by blood, cause specific changes in target cells
● regulate energy use, metabolism and growth, maintain homeostasis
● can have dual role: chemical in endocrine, signal in nervous ex. epinephrine
● Peptide: short peptide sequence, water soluble, cannot pass through phospholipid binds
to receptor on surface, triggers a signal transduction pathway
● Steroid: cholesterol, lipid (not water) soluble, enters through diffusion into cell, binds to
intracellular receptor in cytoplasm or nucleus
Exocrine Glands: produce hormones delivered by ducts (outside body; ‘exo’)
Digestive System- pancreas & salivary | Thermoregulation- sweat glands
Endocrine
stimulus→ endocrine gland→ blood vessel→ target = response
Neurohormone
stimulus→ hypothalamus→ blood vessel→ target = response
●
●
Internal Senses→ Hypothalamus→ Hormones of Autonomic Nervous System
○ Neurosecretory: specialized nerve cells, secrete hormones (hypothalamus)
○ hypothalamus is the integration of the nervous and endocrine systems
Pituitary: at base of hypothalamus, anterior and posterior
○ Posterior: part of hypo, stores/secretes hormones; ADH & oxytocin
Neuroendocrine
○
stimulus→ hypothalamus→ blood→ endocrine→ blood→ target
Anterior: connected to hypo- portal blood vessel, makes hormones; stimulated
or inhibited by hormones from hypothalamus; TSH/ACTH/FSH/LH/GH
■
endocrine/secretory cells of anterior synthesize/secrete→blood
■
PRL-non tropic, GH/FSH may be non-tropic; all anterior are NE
Glucose Regulation-Pancreas maintains blood glucose levels by secreting hormones
Pancreas:
●
Exocrine Cell: 98-99% mass, produces digestive enzymes → s. intestine
●
●
Endocrine Cell: 1-2% mass, scattered, islets of langerhans\
Islets of Langerhans: alpha cells- glucagon, beta cells- insulin; antagonistic/opp
○
hyperglycemia/ ^blood glucose (aft eating)→insulin→body cells uptake glucose
w/facilitated diffusion (transporters activated), inhibit glycogen
breakdown/conversion of amino acid+glycerol to glucose in liver; vBG
○
hypoglycemia/vblood glucose (between meals)→ glucagon→ glucose from noncarb and glycogen breakdown in liver→ ^blood glucose
Situation
After Meal/Hyperglycemia
Between Meals/Hypoglycemia
Hormone
insulin
glucagon
Simulant
increase in blood glucose
decrease in blood glucose
Effect
^glucose uptake, vglycogen breakdown
vglucose
uptake, ^glycogen breakdown
Diabetes: frequent urination; mellitus type 1/2 (insulin/glucose), insipidus (reabsorption)
●
glucose unavailable to body cells→ hyperglycemia: ^blood glucose, hunger, fat for
cellular resp, ^viscosity vflow→ blurred vision, foot infections
●
kidneys excrete glucose→glucosuria (glucose in urine), frequent urination, thirst
Type 1: immune sys attacks insulin
producing cells
Type 2: decreased responsiveness to
insulin
Onset
Childhood
Adult (past age 40), Pregnancy
Molecular
Cause
Insulin deficiency
Insulin resistance (unresponsive receptors)
and deficiency
Cause
Genetic autoimmune disorder
Obesity
Treatment
Daily insulin injections
Exercise & dietary control drugs
Banting & Best (Canadians): nobel prize for insulin isolation
●
remove pancreas from dog→^blood sugar, ^thirst/urination, weaker→diabetes
●
tied off ducts to digestive tract, digestive enzyme making cells shrivel, islets remain
●
isolated insulin from islets, injected into dog→ cured
●
Leonard Thompson: first treatment with insulin injection, 14 year old, 1922
Stress Response: natural, prepares individual to handle stressor, short & long-term
Adrenal Gland: secretes stress response hormones, adjacent to kidneys
Adrenal Cortex: outer portion, long-term stress response
●
CRH: neuropeptide, made in hypothalamus→ ACTH synthesis in anterior pituitary
●
ACTH: tropic peptide, produced in anterior→ adrenal cortex makes corticosteroids
○
sex hormones (testosterone) are also corticosteroids (5 6ring, 1 5ring)
●
●
Glucocorticoid/Cortisol: glucose from fat and skeletal muscle (in liver), when out of
carbs, suppresses immune system, antihistamine/inflammatory, ^glucose
Mineralocorticoid/Aldosterone: ^kidney salt/water reabsorption, ^BP, ^oxygen flow
Location
Hormone
Stimulus
Stress
Hypothalamus
Corticotropin-releasing hormone (CRH)
Anterior Pituitary
Adrenocorticotropic hormone (ACTH)
Adrenal Cortex
Corticosteroids: glucocorticoid- cortisol, mineralocorticoid- aldosterone
Effect
^glucose production + oxygen delivery
Adrenal Medulla: inner potion, short-term stress response (fight/flight)
●
stress excites nerves→ acetylcholine (ACh)→ adrenal medulla→ catecholamines
●
Catecholamines: synthesized from tyrosine | (nor)epinephrine=(nor)adrenaline *31
●
^metabolism/energy (glycogen→glucose→ATP, fatty acids released, vkidney and
digestive activity), ^oxygen→ ^BP+flow, ^breathing, redirect blood to vital areas (brain,
heart, skeletal), increased alertness→ stimulates f(l)ight
●
Epipens: epinephrine reduces swelling, opens airways, maintains BP
Stress
Short Term
Long Term
Hormones
Epinephrine, Norepinephrine
(catecholamines)
Glucocorticoid- cortisol
|
Mineralocorticoid- aldosterone
Energy
Glucose from glycogen
Glucose from non-carb source
Oxygen
^<3 rate,BP, flow, resp rate, reg vessel size
^reabsorption of salt/water, blood volume, pressure, flow
(corticotropins)
Hypersecretion/Cushing’s Disease: overproduction of glucocorticoid/cortisol
● mimics diabetes (hyperglycemia, glucosuria, vprotein)
● cause: excess ACTH (from pituitary tumor) cure: surgery/radiation
● effects: body fat in abdomen, face, above shoulder blades (moon face/buffalo hump),
thin appendages, muscle/bone weakness, prone to bruising and fractures
glucocorticoid supplements (anti-inflammatory- asthma / arthritis / joint injuries | immune
suppressant- lupus/autoimmune disease) have cushing’s effects
Karoshi: death from overwork→ heart attack/stroke, chronic increase in cortisol (japan)
Hyposecretion/Addison’s Disease: inadequate cortisol, autoimmune/adrenal gland disorder,
need corticoids→ weight loss, nausea, abdominal pain muscle weakness (JFK)
Metabolism
Thyroid gland - one of the largest endocrine glands, makes thyroid hormones
● Location: base of neck, ventral surface of trachea, below/anterior to larynx
● Functional unit: follicle
● Structure: 2 lobes, 4 cm long/1-2 cm wide, connected by narrow neck (isthmus)
Thyroid hormones (require iodination): Peptide hormone from amino acid tyrosine unlike
most peptides→hydrophobic & diffuse into nearly every cell, not v soluble in blood
●
●
●
●
●
Receptor: intracellular (in nucleus), greater affinity for T3 than T4
Reg. metabolism: ^glucose metabolism, protein synth, O2 consumption (BP, ♥rate)
Reg. growth/tissue differentiation: digestion, reproduction, bone, muscle tone, nerve cells
T3: 3 iodine 0.3% in blood ~20% made by thyroids, 4x potent than T4, reg metabol
T4: 4 iodine 0.03% in blood ~80% made by thyroids, not very potent, T3 storage
Thyroid regulation: decrease in metabolic rate→hypothalamus→high levels of T3/T4 in blood
turn off TRH/TSH production; otherwise constantly made
Location
Hormone
Hypothalamus
TSH releasing hormone/thyrotropin releasing hormone (TRH)
Anterior pituitary
Thyroid stimulating hormone (TSH)
Thyroid gland
Thyroid hormones T3 and T4
Hyperthyroidism: ^T4, ^glucose metabolism (weight loss, ^appetite), anxiety, ^heat release
● overactive gland/surplus thyroid hormones, inflammation (thyroiditis), pituitary tumors,
excessive iodine intake/thyroid hormone meds
● Anti-Thyroid Drugs: suppressive, block hormones to blood, prevent iodine entry
● Radioactive Iodine Therapy: when drug therapy fails or post radioactive iodine-131
damages thyroid cells over time, thyroid gland shrinks
● Surgery (thyroidectomy): removal of all or some parts, may need post-surgery drugs
Goiter
enlarged thyroid gland; overactivity
low iodine→low T3/T4, compensates; overworks
Plummer’
s
lumpy, huge thyroid/neck
toxic multinodular goiter (many nodules/lumps)
Grave’s
protruding eyes, eye irritation and
double vision (8x in women 20-40)
autoimmunity- thyroid stimulating immunoglobulin
(TSI); target TSH receptors, no neg feedback
Hypothyroidism: vT4, vglucose metabolism (^weight, fatigue, vheart rate), 4x women 35-60
● Cause: low iodine, poor hormone production, after radiation therapy/thyroidectomy
●
Hashimoto’s thyroiditis: autoimmunity; attack gland→inflammation, 20x women 30-50
Treatment: hormone supplements
Thyroid Issue
Hyperthyroidism
Hypothyroidism
Weight
Loss, good appetite
Gain
Body function
^poop, light/absent menstruation
Constipation, heavy menstruation
Temperature
Warm/moist skin, hot
Cold
Neurological
Fatigue, insomnia, irritability,
nervousness
Fatigue, slowed thinking
Others
Bulging eyes, goiter
Dry skin
Calcium Regulation: parathyroid hormone, calcitonin (antagonistic) *slide 39*
Storage: 99% bones | cells: mitochondria, ER | skeletal muscles: sarcoplasmic reticulum
Function: muscle: amt changes when muscles contract | nerve: release neurotransmitters
Bone cells: osteoblast: make bone, use Ca, osteoclast: breakdown bones→Ca in blood
Parathyroid gland: 2 behind/adjacent to each thyroid lobe, 4 small ovals
● Parathyroid Hormone: peptide hormone, continuously produced (tonic secretion),
stimulated by a decrease in blood Ca (hypocalcemia)
● bone cells decomposed to release stored Ca into blood
●
kidney reabsorbs calcium, vitamin D precursor→vitamin D
Vitamin D: steroid hormone, reinforces PTH (^Blood Ca) when active
● Ingested in food or formed in skin when exposed to sunlight
●
Targets: bone→releases Ca | intestine→stimulates absorption of calcium
Calcitonin: peptide hormone from thyroid gland
● Stimulated by ^blood Ca (hypercalcemia) PTH antagonist: decreases blood Ca
● Bone: stimulates Ca uptake, inhibits osteoclasts, less bone removal
● Kidney: inhibits Ca reabsorption, ^rate of Ca loss by urine, ^[Ca] in urine
● Intestine: inhibits Ca absorption
Hypoparathyroidism: absent parathyroid at birth/accidental removal w/thyroid removal
● Symptoms: hypocalcemia, sensitive nerves, uncontrollable spasms of limbs
Hypocalcemia: deficient calcium→tetany: ^sensitivity of nerves→spasms, seizures
● Treatments: daily Ca and vitamin D supplements
Hyperparathyroidism: parathyroid tumor→kidney stones, osteoporosis, depression/fatigue
constipation, peptic ulcer, pancreatitis (Stones, bones, groans, moans, overtones (SBGMO)
● Treatment: removal of parathyroid tissue
Osteoporosis: loss of bone density→fragility ^risk fractures, joint pain, kyphosis (hunchback)
●
Causes: hyperparathyroidism (high PTH levels), over activity of osteoclasts,
hypovitaminosis D (lack of vitamin D)
Growth
GH/somatotropin: peptide (~200 amino acids), affects somatic cells, half-life 20-30 min
● Binds directly to target bone/muscle cells, stimulates growth/mitosis/metabolism
○ Hypertrophy: ^size/volume of cells ie ^bone thickness
○ Hyperplasia: ^# of cells, proliferation rate ie. ^bone length
Function: Indirect GH: tropic hormone→liver, produce IGF (insulin-like growth factor)
●
IGF-1→most cells (muscle/cartilage/bone/skin)→hypertrophy/hyperplasia
Growth Regulation: neuroendocrine pathway
Negative feedback: High IGF-1 → GHIH/SS, vGH | High GH → inhibits GHRH
Hypothalamus
Growth hormone release hormone (GHRH)
Growth hormone inhibiting hormone (GHIH) = somatostatin (SS)
Anterior pituitary
Growth hormone (GH) = somatotropin
Liver
Insulin-like growth factor (IGF)
GH Secretion: in bursts (not continuous), vw/age, ^sleep, ^night, sleep patterns affect GH
● ^GH production: exercise regularly, 8 hours of sleep, protein-rich diet, avoid stress
Dwarfism: 200+ different causes, 2 major types
Proportionate: entirely small, ‘pituitary dwarfism’, GH absent during child’s development
Disproportionate: “achondroplasia”, common (70%), some parts smaller
● Autosomal dominant, mutation on chromosome 4
●
Gene→long bone growth→legs bend→walking uses ^energy
Gigantism: continuous GH in childhood, open epiphyseal plate (^bone length)
● Cause: benign pituitary gland tumor; secrete ^GH, skull^ but brain unchanged
● Symptoms: poor blood flow, ^muscle mass/weaker muscle
○
Excess GH→salt in muscles→swelling (hypotonic)→weaker muscles
● Tallest: Robert Wadlow: 8f11”, currently Sultan Kosen from Turkey, 8f1”
Acromegaly: lateral growth ^GH (adult), closed epiphyseal plate (no ^bone length)
● Bone width^: forehead, eyebrows bulge, ^cheekbones/jaw, jaw teeth widespaced
●
Soft tissue hardens: larynx→deep voice|tongue/lips→hard breathing|nose cartilage
●
Heart tissue stiffens: cannot contract/relax, ventricle hard to fill, bigger→^pump
●
Impaired movements, muscle numbness, early death
○
●
●
^bones→crush peroneal nerve in knee which moves foot/lower leg
Lung defects: ribs expand, diaphragm stretched thin/less elasticity+breathing
Progression of Acromegaly is slow
Nervous System-transmit information rapidly, form response
Function
Description
Components
Sensory Input
Detection of stimulus
Sensory receptor/ Afferent/Sensory neurons
Integration
Processing in the brain
CNS (Brain + Spinal cord)
Motor Output
Response in other part of body
Effector cells/ Efferent/motor neurons
Central vs Peripheral Nervous System:
CNS
PNS
Brain/Spinal cord
Afferent (sensory) and efferent (motor) neurons that connect to CNS
PNS→Sensory (external/internal) or Motor (autonomic/somatic)
●
Autonomic→(parasympathetic/sympathetic)
Sensory/Afferent Division: of PNS
External Senses: somatic (skin/muscle/joint) | special (sight/sound/smell/taste/equilibrium) use
exteroreceptorsv
Receptor
Mechano
Photo
Chemo
Thermo
Noci(ceptor)
Detects
pressure/movement
light
chemicals
temperature
pain
Location
skin/muscle/ears
eyes
nose/mouth
skin
skin
Internal: visceral (fullness of stomach, blood pressure), uses interoreceptors
Motor/Efferent Division: integration center signal→effector cell (responds to stimulus)
Somatic Senses: external/internal stimuli, sends signal to skeletal muscles (voluntary)
Autonomic Senses: sends signal to smooth/cardiac muscle and organs (involuntary)
● Sympathetic: prepares for stress (Epinephrine/norepinephrine) vusually antagonistic
● Parasympathetic: restores body to normal balance (Acetylcholine)
Sympathetic
arousal/energy generation
Parasympathetic
calming
^heart rate, ^lung gas exchange
vheart
rate vlung gas exchange rate
Nerve: group of neurons bundled together
Neuron: structural/functional unit/cell, when mature- cannot divide
Excitable: large/rapid electric signals/membrane potential change possible (muscle/neuron)
Components of a neuron
Components
Description
Function
Cell body (soma)
Main part, has nucleus/organelles
basic (protein synthesis metabolism)
Dendrites
Short, branched extensions
receives input from other neurons
Axon (nerve fiber)
1 per cell, extension, may branch
sends information
Axon hillock
Site where axon originates
where action potential initiates
Synaptic terminal
End of axons
contains/releases neurotransmitters
Impulse Conduction: dendrites→cell body→axon hillock→axon→synaptic terminal
Types of neurons: Sensory neurons, Interneurons (CNS), Motor neurons
Sensory: afferent, signals from sensory receptors→CNS, in neuron clusters (ganglia)
Interneuron: association neuron, signals from sensory neurons→effector neuron
● excitatory or inhibitory
Motor: efferent, on tissues that respond (muscle contraction, gland hormone secretion)
Supporting/Glial Cells: 90% nervous cells, structural/metabolic support to neurons
● Astrocytes (CNS): star shaped, communicate with neurons, no conduction
○ Blood-Brain Barrier: Seal off blood vessels in brain (tight junctions)
● Oligodendrocytes (CNS)/Schwann cells (PNS): insulate electrical axon impulses
○ Forms Myelin Sheath: lipid molecules, poor conductors, electric insulation
■ Neurilemma: myelin sheaths around each other (like insulated wires)
■ Nodes of Ranvier: gaps between cells that wrap around the neuron
Nerve circuits: transmitting/presynaptic (axon)→synapse→target/postsynaptic (dendrite)
Divergent: 1 presynaptic neuron→many postsynaptic (visual info; photoreceptors→brain)
Convergent: several presynaptic→ 1 postsynaptic (sight/touch/sound identifying objects)
Circular: cycle from neuron to neuron to neuron etc. (memory)
CNS
Organs
Bone
Fluid-filled cavity
Brain
Skull
Ventricles
Spinal Cord
Spinal Column, spine,
vertebrae
Central Canal
Ascending Tract: Receptors→Somatosensory area of Cerebral Cortex
Descending Tract: Motor Area of Cerebral Cortex→Skeletal Muscle
Paired Spinal Nerves: originate in the spinal cord and innervate the entire body
Paired Cranial Nerves:originate in brain and innervate the head/face
Cerebrospinal fluid (CSF): in CNS cavities, from blood filtration, shock absorber (cushion)
● flows through subarachnoid space, carries nutrients, hormones, white blood cells
●
nutrients→brain via CSF in middle of spinal cord and inner layers of meninges
Meninges: tough/elastic connective tissue in skull/spinal column, around brain/spinal cord
●
3 layers: dura→arachnoid→pia
●
Protection: Blood-Brain Barrier (blood vessels in subarachnoid space btwn ara/pia)
○
●
stops substances in vessels→brain, selectively allows oxygen, glucose, etc.
Meningitis: inflammation (virus/bacteria) antibodies---/→brain, need quick medical treat
Axon Bundling: white matter: myelinated axon|gray matter: unmyelinated, axon/dendrite
● white matter usually surrounds gray matter in brain+spinal cord, slide 19-20
Anatomy of Brain: fore/mid/hind
Hindbrain: in brain stem: lower brain, directs data from higher brain (coordination/movement)
Medulla Oblongata: brain stem base, controls involuntary muscles; (♥rate, vasodilation etc.)
● Descending axons w/movement instructions crisscross; right brain control left body
Pons: bridges info btwn cerebellum+medulla oblongata
Cerebellum: unconscious coordination: posture/balance|voluntary motor skills: write/walk
Midbrain: sensory info (eyes, ears, nose) superior colliculi: visual, inferior colliculi: auditory
Forebrain: thalamus/epithalamus/hypothalamus/pituitary lower, cerebrum- higher brain
Thalamus: relay station: sensory input→thalamus→cerebrum→motor output→thalamus
Epithalamus: has pineal gland, secretes hormones w/light+seasonal change
Hypothalamus/Pituitary: homeostatic regulation/hormone production
Cerebrum: largest, most highly evolved in mammalian brain, 2 hemispheres, 4 lobes
● Corpus Callosum: white matter, connection/communication btwn hemispheres
● Cerebral Cortex: gray matter, outer covering (mammals) 5 mm, 80% brain mass, 6
neuron sheets on surface, convulsions ^SA, ^cognitive ability, sophistication (?)
● Frontal Lobe: voluntary movement, reasoning, integrate sensory info from lobes
○ modulates emotions based on socially acceptable norms
● Temporal Lobe: processes hearing
Hippocampus: long-term memory Amygdala: memory and emotions
● Occipital Lobe: primary visual processing, coordinates info from retina
● Parietal Lobe: touch/temp (somatosensory cortex) taste, visuospatial analysis (#s/ratios)
Integrative Function: specialized function; integrates various areas of the cerebrum
Sensory Input Processing: sensory input→primary sensory areas (lobes)→adjacent association
areas (lobes, assess info significance)→frontal lobe association area (make motor response)→
primary motor cortex (direct skeletal muscle movement)→motor output
●
Primary Cortex: somatosensory cortex integrates sensory info (skin/muscle/joints)
motor cortex sends signal to skeletal muscles
Sensory Input
Primary Sensory Areas in lobes
Adjacent association area
Visual
Occipital
Visual
Hearing
Temporal
Auditory
Smell
Frontal
Frontal
Taste
Parietal: taste
Somatosensory
Touch
Parietal: primary somatosensory cortex
(pain/pressure/temp/limb position)
Somatosensory
Lateralization: brain function allocation to right/left hemisphere during brain dev. (child)
Left Hemisphere
Right Hemisphere
●
●
●
●
●
●
●
●
●
●
Language
Math, logic operations
Processing of serial sequences of info
Processing fine visual/auditory details
Specialized in detailed activities required for
motor control
Pattern recognition, spatial relationships
Face recognition/emotional processing
Music
Multi-tasking
interpreting whole context
Language/Speech Areas:
Areas
Broca
Wernicke
Location
Frontal Lobe
Temporal Lobe
Function
Speech Production (motor)
Speech Comprehension (sensory)
Damage
can’t understand speech/speak
say words, don’t make sense
Reading text aloud: visual cortex + broca (seeing, speaking, without understanding)
Determining meaning to generate words: frontal lobe + wernicke
No Talking
Talking
No Understand
Visual (passively viewing words)
Broca (speaking words)
Understand
Auditory, Wernicke (listening)
Wernicke, Broca (generate words)
Limbic System: primary emotions (bonding, nurture infants) +emotion 4 survival (sex/eating)
● Hippocampus, olfactory cortex, thalamus, hypothalamus, amygdala
● Amygdala: temporal, info from hippo, empathy (face feelings), emotional memories
○ infants learn right/wrong when given smiles/frowns
Memory/Learning: nerve cells make new connections as skills develop, hard to unlearn
● Long-Term Memory: hippocampus, enhanced via repetition, influenced by emotional
states and association with previously stored information
● Short-Term Memory: in frontal lobe, limited capacity/duration (7 items, 30 secs)
○ Bottleneck in memory system, limits info transferred to long-term
Functional Changes in Synapses
Long-term potentiation (LTP): postsynaptic ^response to stimuli, induced w/brief repeated action
potentials→ strongly depolarize postsynaptic membrane, (link to mem/learning)
Long-term depression (LTD): postsynaptic, vresponse to action potentials, induced by repeated,
weak stimulation ex. cannot smell after prolonged exposure
Neuronal Plasticity: mature neurons adapt to environ (learning or compensation after disease/injury)
● Short Term: enhancement of existing synaptic connections
● Long Term: physical changes (formation of new synapses)
● Rehab after: strokes, epilepsy, car crashes, loss of limbs, being in Space
Nerve Signaling-p = potential
Voltage: diff in electric p (charge separation) or energy in charged ions (E/Q) btwn 2 points
Membrane potential (Vm): voltage across a membrane
● outside nerve cell: excess cations (+), inside of nerve cell: excess anions (-)
●
measured w/voltmeter: Vm=Vin–Vout→Vin=potential inside | Vout= potential outside=0
● Resting potential (VR= -70mV): membrane potential of a neuron at rest
1. Ion distribution: pool of neg proteins, amino acids, sulfate, phosphate etc. in neuron
● Large molecules that cannot cross membrane
2. Membrane permeability: more permeable to K+ (efflux) than Na+ (influx)
● Charged ions cannot directly diffuse across cell membrane (lipid, nonpolar)
● Transmembrane proteins regulate movement of ions
○ Ion Channels (facilitated diffusion/passive) | Pumps (active)
Passive transport of ions: dependent on electrochemical gradient
● Chemical gradient: [ion] | Chemical force: high to low [ion]
● Electrical grad: relative electric charge | E. force: [cation]<=>[anion] (mem potent)
○ Equilibrium potential (Ex): potential w/no net movement of ions
Establishing Equilibrium with K+ (assume cell only permeable to K+)
● EK = –85 mV, more negative than resting potential (–70mV), must move cations in
●
Chem force→K+ diffusion out, inside cell→more negative→E force pulls K+ back in
● Eq when chemical/electrical forces are in opposite directions, equal in magnitude
Establishing Equilibrium with Na+: permeability: chemical force = electrical force = influx
Establishing Equilibrium with K+ and Na+: resting potential maintained: K+ + Na+ move
●
keep -70mV: K+ efflux>Na+ influx, more permeable to K+→ more open K+ channel
Establishing Steady State: over time if cell left unchecked...
●
Na+ influx→less negative cell→steady K+ efflux→concentration gradient dissipates
●
This doesn’t happen unless death→avoid equilibrium, keep gradient to stay alive
3. Na+/K+ pump: 3 Na+ out for every 2 K+ in
● Use ATP to drive active transport, maintain ionic gradients, restore steady state
Types of ion channels
● Ungated: open all the time
● Voltage-gated: open/close to membrane potential changes (K+/Na+ axon channels)
● Chemically-gated: open/close to chemicals (dendrite receptors open when NT bind)
Polarization
●
Hyperpolarization: ^voltage in membrane→more negative (K+ outflow, Cl- inflow)
●
Depolarization: vvoltage across membrane→less negative (^Na+ inflow)
Potential
Graded potential: magnitude of polarization depends on strength of stimulus
● Decremental: magnitude decays/degenerates as it spreads
●
ex ^stimulus=^open channels→^cell ion permeability→^membrane p change
Threshold potential: when an action potential occurs, around –50 to –55 mV
●
After threshold stimulus intensity doesn’t change magnitude, graded→action p
Action potential: only happens in axon|trigger zone: axon region of 1st action p occurs
●
Pos feedback ex: depolarization to threshold potential→^depolarize to action p
●
All/nothing: non-graded; magnitude independent of stimulus strength @threshold
○ Amplitude (magnitude) of all action potentials is constant regardless of stim
○ Frequency coding: stim strength/duration relates to action p frequency
Phases of action potential: s=slow, f= fast
resting→threshold→depolarization→repolarization→undershoot
Phases
K+ gate (s)
Na+ activation gate (f)
Na+ inactivation gate (s)
mem. pot.
Resting
Closed
Closed
Open
-70 mV
Threshold
Closed
Some open
Open
-50- -55 mV
Depolarization
Open slowly
All open
Closing slowly
+35 mV
Repolarization
All open
Open
All closed
-70 mV
Undershoot
Close slowly
Closed
Closed
-75 mV
Propagation: unidirectional, not bi bc undershoot/inactivation gate
● Action potential “travels” by repeated regeneration along axon
● Depolarization by influx of Na depolarizes neighboring region above threshold
Refractory period: neuron insensitive to depolarization in undershoot (Na gates closed)
● prevent backwards action p, limit max frequency; action p can be generated
Factors affecting speed of conduction
● Axon diameter; larger = faster; less resistance
● Myelination; axon only exposed to ions in ECF at nodes, No action p btwn nodes
○ Voltage-gated ion channels in nodes of Ranvier (unmyelinated region)
Saltatory conduction: allows faster signal conduction along axon
●
Current generated by action p at node→next node, stimulates new action potential
● Na+/K+ exchange can only occur where axons are exposed to extracellular fluid
Synapse: cell junction that controls communication between a neuron and another cell
● 3 main types of connections where synapse would be observed:
○
○
○
Sensory input (afferent): sensory receptor & sensory neuron
Integration: neuron & neuron (interneuron)
Motor output (efferent): motor neuron/muscle cells, neurons/glands
Electrical synapse: presynaptic current→postsynaptic cell through gap junctions
● Gap junctions: pores/channels btwn adjacent cells; ions/small molecules can pass
● Found in giant axons in crustaceans, not common in vertebrates
● Pro: rapid transmission of action potential from cell to cell | Con: harder to regulate
● *****slide 54= anatomy*****
Chemical synapse: uses neurotransmitters, non continuous current
1. Presynaptic membrane depolarized by action potential
2. Voltage-gated Ca2+ channels open, Ca2+ enters cell
3. Stimulates exocytosis of synaptic vesicles w/NTs
Effect of changing Ca levels: Frequency of AP → [Ca] → [NT]
●
Ca2+ channels close, Ca2+ active transport out of axon terminal→resting level
● If another action potential arrives soon after previous, then Ca2+ levels^
Synaptic cleft: small gap separating pre/postsynaptic cells (not electrically coupled)
●
Signal conversion: electrical → chemical → electrical
Synaptic vesicles: sacs at the synaptic terminal, contains neurotransmitters
●
Neurotransmitter: intercellular messenger, presynaptic cell→synaptic cleft
Neurotransmitters (NT): each neuron usually only secretes 1 type
NT
Description
Examples
Acetylcholine
(ACh)
Most common
Acts on motor neurons and skeletal muscles
Amino acids
Affects mainly the CNS
Glutamate (+ CNS), GABA (- brain), glycine (- spinal
cord)
Neuropeptides
Short chain of amino
acids
Endorphins (- pain), Substance P (+ pain)
Biogenic amines
Derived from amino
acids
Catecholamines (tyr), serotonin (trp), dopamine
(phe/tyr)
Gaseous signals
No synaptic vesicles
(made as needed)
Nitric oxide
●
Receptors (gated ion channel part) on post-synaptic membrane recognise 1 NT
●
NT binds, gates open, allow specific ion in (i.e. Na, K, Cl)→ chemically gated
Postsynaptic potentials (PSP): dendrites→axon hillock, (graded, not action)
● Graded potentials: vary in magnitude w/NT, decremental (degenerates w/distance)
Excitatory postsynaptic potential (EPSP)
● Excitatory synapse: ^chance AP generation, depolarization, positive net flow in cell
● NT binding to receptor opens gated Na+ and K+ channels
○ electrochemical gradient diffusion: Na+ enters, K+ leaves, Na+ > K+ force
● For AP, EPSP: strong enough to depolarize to threshold potential @axon hillock
Inhibitory postsynaptic potential (IPSP)
● inhibitory synapse: vchance AP generation, hyperpolarization, neg net flow in cell
● NT binding to receptor opens gated K+ and Cl- channels
● Diffusion down electrochemical gradients: K+ leaves, Cl- enters
Summation: additive effect of post-synaptic potentials (PSP) @axon hillock
● Can result in stimulatory effect (depolarization) or inhibitory (hyperpolarization)
● Ex: 1 EPSP usually not strong enough to trigger AP (same application to IPSP)
○ EPSPs working on same postsynaptic cell can have cumulative impact
● IPSP and EPSP can counter each other’s effects
●
Spatial summation: several diff synaptic terminals (usually from diff presynaptic cells)
stimulate same postsynaptic cell→additive effect on membrane potential
●
Temporal summation: chem transmission from one+ synaptic terminal occurring close
in time affecting postsynaptic membrane before voltage→resting potential
NT removal: enzymatic degradation/reuptake in presynaptic cell, diffusion out of cleft
● Consequence: ensures NT affect brief/precise, lets next action p transmit
Communication across a synapse
Action potential→Ca channels open→Ca enters, release NT w/exocytosis→NT diffuse across
synaptic cleft→bind to receptor on postsynaptic cell→postsynaptic response→ removal by
enzymatic degradation/reuptake by presynaptic/diffusion out of synaptic cleft
Special Senses
Sensation: action potential→brain via sensory neurons Perception: interpretation of stimuli
Sensory Reception: Detection of the energy of a stimulus by sensory cells
Sensory Receptors: Specialized neurons/epithelial cells in sensory organ (extero vs intero)
Process of Sensory Reception: sensory transduction→amplification→transmission→integration
Sensory Transduction: stimulus energy→membrane potential change in receptor cell
●
Receptor potential: Graded potentials as a response to stimuli, produced by ^
○
ex. pressure stretches membrane, ^ion flow|sugar bind→Na channel opens
Amplification: strengthen stimulus energy, otherwise too weak to enter nervous system
Transmission: conduction of impulses to CNS from receptor potential→action potential
● intensity of receptor potential=frequency of action potential
● Receptor can be afferent sensory neuron or can be diff cell (ex. muscle)
Integration: process info|Sensory adaptation:integration w/vresponse w/continued stim
● threshold varies with cell and condition | can’t smell when used to smell
5 Senses: specialized organ senses: vision, hearing, smell, taste somatic sense: touch
Vision:
Retina: w/light-sensitive cells-convert light→ electrical signal→optic nerve→occipital lobe
Cones: 6 million, need/function best in bright light, distinguish colours
Rods: 125 million, light sensitive, triggered by 6 photons, only sees monochrome
● responsible for night vision (if dark, we see in black and white)
Photoreceptor: specialized neurons, convert light info→electrical signals (rod+cones)
Opsin: light-sensitive membrane proteins, 4 types -1 for rod, 3 for cone
Retinal: light absorbing pigment from vitamin A
● Rhodopsin:Opsin and retinal complex in rod
● Photopsin: Opsin and retinal complex in cone: 3 types (3 primary colours of light)
S-cones: short wave, blue| M-cones: medium wave, greenL-cones: long wave, red
○ Colour blindness: Sex-linked genetic disorder, deficiency of photopsin
Phototransduction (darkness): No light→high cGMP→Na in→NT out→ EPSP or IPSP
●
cGMP→opens Na channels→membrane depolarizes→ release glutamate (NT)
Postsynaptic cell: bipolar; glutamate- inhibitory/excitatory depending on bipolar cell type
Photoisomer:Molecule changes shape when it absorbs photon of light
●
In light: photoreceptors hit→cis→trans retinal, detaches from opsin→opsin breaks down
cGMP→close Na channels→membrane hyperpolarizes→stops glutamate
Vision (sensory reception): photoreceptor → bipolar cells → ganglion cell
action potential @ganglion cell, impulse transmitted; optic nerve→occipital lobe
Transduction/Amplification:rod/cone | Transmission:optic nerve | Integration:occipital lobe
●
In low light: enzyme→ retinal+opsin→ rhodopsin
Sensory adaptation in vision:
●
Rods: long ^[photons] bleaches rods: ^rhodopsin→retinal + opsin
●
Cones: Additive Colour Theory: afterimage is opp colour of original
Afterimage: cones vsensitivity→blank space, adapted cones weak, others strong
●
Primary Colour (opp secondary): red (cyan), green (magenta), blue (yellow)
Hearing: volume: amplitude | pitch: frequencies (simulates hairs in diff coachella parts)
soundwave→eardrum→3 midear bones (malleus/incus/stapes) amplify x22→
tap coachella→cilia bend in response→cochlear nerve→temporal lobe
●
●
Coachella: 2 chambers w/fluid cochlear duct separates, loud noises damage cilia
Organ of Corti on duct floor: auditory receptors on tectorial membrane
Auditory Transduction:
1. Sound waves=pressure through coachella, dissipate at round window
a. vestibular canal→apex→tympanic canal→^cochlea→tip→vcochlea
2. Tectorial mem vibrates→bends hair→ion channels open/release NT at synapse
3. Sensory (postsynaptic) neurons (cochlear nerve) action potential→temporal lobe
Stability and Balance: Semicircular canals: above cochlea, filled with “gel” + otoliths
● Otoliths: “ear stones”, CaCO3 granules, denser than regular gel
●
Balance: gravity→ oliths pull down hair cells, direction of bend=position→brain
Terms
Population- number of all organisms of the same species, in the same geographical area
Habitat- place where an organism or a population lives; includes biotic and abiotic
Geographic Range- geographical area for the distribution of the species
Ex. Habitat = Forest, Geo Range = Northern US and Canada
Similar: where organism thrives, Diff: habitat within a range, not using location
Density- # of individuals per unit of area or volume (=N/A)
Crude Density- # of individuals in the entire habitat; easiest to determine, used often
Ecological Density- # of individuals in the area used by individuals; more accurate
● useful when population is unevenly dispersed (clumped)
● not useful when habitat changes with species’ developmental stage
Dispersion- distribution pattern of a population
● Clumped: herd-like mentality, resources are abundant in a few areas, safety in #s
● Random: neutral, resources are very abundant and are everywhere
● Uniform: territorial or high pop density, resources are
Sampling- measure a portion of the population; apply it to whole
● Transect: line placed across a community of organisms, usually in a string between 2
markers. Subsequent transects are arranged equal distances from each other
○ Point: string is marked at equal intervals to indicate where the count is to be
taken; sample plots are randomly located between the intervals
○ Continuous: whole area along the line is counted
○ Belt: multiple quadrats are taken from the line
○ Math: N1/A1=N2/A2
○ Usage: determine distribution; good when environmental gradients are present,
low density population, large organisms
● Quadrat: use on sessile (immobile), or slow organisms; use math in above
● Mark-Recapture: A few are marked of the entire population then released. Some of the
population is recaptured. Good for mobile organisms
○ Math: M1/N = M2/N2; N= total pop, N2= # captured
Capture
#1
#2
Marked
10
2
Total Population
x
20
x = 100
Tracking- monitoring/following an individual organism
Demography- study of the changes in the characteristics of a population
P2 = P1 + (B+I) - (D+E)
Life History- all traits that affect an organism’s reproduction and survival
Life Table- summarizes demographic characteristics of a population; monitor cohort til death
● originally used by insurance companies to measure mortality rates
Cohort- group of individuals with similar ages
Survivorship Curve- number or proportion of individuals surviving at each age for a given
species or group
● Type 1: youth survivorship is high, mortality is amongst elders; mammals
○ long gestation, long parental care, large size
● Type 2 (steady): individuals die at equal rates regardless of age; birds/reptiles
○ medium gestation, medium parental care, smaller sized
● Type 3: most die at youth, lower death rate later on; fish
○ very short gestation, short parental care, tiny size
Fecundity- average # of offspring produced by a female over her lifetime; measurement of the
potential for a species to produce offspring; intrinsic rate of increase is similar
● Age of Sexual Maturity: younger = up
● Max Reproductive Age: older = up
● Gestation Length: longer = down
● # of Offspring: more = up
● Parental Care: longer = down
● Sex Ratio: more females = up
Population Change- ΔN = N2 - N1 or (B + I) + (D+E)
● 2 dogs had 101 puppies. 99 of them were stolen. 97 were found and returned. None of
them died: find final pop, and growth rate
○ E = 99, I = 97, D = 0, ΔN=?, B = 10 | N1 = 2
○ ΔN = 101+97-(0+99) = 99
○ Final Pop = 99 + 2 = 101 | Growth= 99/2 = 495%
Growth Rate- ΔN/N1 -population size as a ratio
● The growth rate for a population of 90 field mice in 6 months is 429%. If the number of
births was 342, the number of deaths was 43, and there was no emigration, calculate the
number of mice that migrated into the area.
○ E=0, I-?,D=43,B=342, N1 = 90
○ ΔN/N1 = ΔN/90 = 4.29; 0*4.29 = ΔN
Population Growth Models-
●
●
Exponential (J curve)- pioneer populations show this
Logistic (S curve)- rate accelerates until the point of max growth, then slows down to
carrying capacity (0 environmental resistance left); sigmoid
○ Carrying Capacity (K)- birth rate and death rate are equal
○ Zero Population Growth (ZPG) when N = K, r = 0
Biotic Potential (r)- highest possible growth rate under ideal conditions; potential not actual
Intrinsic Rate of Increase (rmax)- highest possible growth rate for a population when no
external factors are acting on it; no environmental limits
Species Interactions
● Predation- one kills prey; cannibalism is under this +/○ Predator Prey Cycles: sinusoidal population cycles; large/small alternate
● Herbivory- organism feed on a photosynthetic organism; unlike predation the one being
fed on might not die; ex. caterpillar eats a small part of the leaf
● Symbiotic Relationships
○ Parasitism- parasite harms host (+/-)
○ Mutualism- both benefit (+/+) oxpecker bird + animals
○ Commensalism- benefit/neutral (+/0) orchid on top of tree
○ Amentialism- neutral/harm (-/0) taller plant blocking sunlight