PHYB 301
Human Physiology
Dr. William R. Law
Room 203A, CMW
6-7622
wrlaw@uic.edu
http://www.uic.edu /~wrlaw
Office hours:
6:30-8:30 AM
12:30-1:30 PM
Basic cell physiology,
membranes, and
the membrane potential
Why study pathophysiology?
Homeostasis: the foundation of Physiology
When things go right: a balance of interactive and varied
functions at all levels of organization
• The body is considered from the perspective of the
interactions of different organ systems
• Organs are considered from the vantage of the
interactions of different cell types.
• Cells are viewed from the perspective of the interactions
of different structures and organelles.
• Structures/organelles from the perspective of
interactions of different molecules
Homeostasis: the foundation of Physiology
When things go wrong: the balance has been disrupted, or
a new, deleterious balance has been instituted.
PATHOPHYSIOLOGY
• Teleological approach: molecules, organelles, celles,
organs, etc, fulfill a bodily need.
• Mechanistic approach: molecules, organelles, cells, organs,
etc, just do.
Homeostasis: the foundation of Physiology
Homeostasis occurs through key regulatory paradigms to achieve
“steady-state” conditions
 Feedback: the “effect” influences the “cause”
 thermostat
 Hierarchical communication: there is a “command”
structure controlling an outcome.
 Hypothalamus-pituitary-adrenal axis
 Adaptation: the steady-state is changed to accommodate a
new situation
 Altitude
Why cellular physiology?
The cell is the smallest unit capable of carrying out the processes
associated with life.
Classical Properties of
Living Organisms:
How cells fulfill these criteria of
Living Organisms:
Reproduction
Nutrition
Respiration
Excretion
Irritability/respond
Movement
Growth
Cell replication
Nutrition
Respiration
Excretion
Respond to environment
Movement within and externally
Grow in number and size
Organization of the cell
• Membranes
– Plasma membrane encompasses the functional cell unit
– Membranes segregate most other individual components of the
cell
• Nucleus
• Organelles
• Cytoplasm - suspension of fluid with various cellular elements
Double membrane
Cristae
Double membrane
Cristae
Matrix
Mitochondria Cellular Power Plant
• Unique Characteristics:
– Contains its own DNA (maternal lineage only)
– Double membrane
• The inner memrane is heavily folded into "cristae"
• The gel-like fluid "matrix" contains enzymes for production of adenosine
triphosphate (ATP)
• Energy conversion
– C-H bonds of substrate (food) is converted to high energy phosphate
bonds through the citric acid cycle (also called the Kreb or
tricarboxylic acid cycle).
• Hydrogen atoms carried by nicotinamide adenine dinucleotide (NAD) and
flavine adenine dinucleotide (FAD)
*importance of niacin and riboflavin
• Electrons carried through a very ordered series of reactions to incoporate
energy into usable form (ATP)
GDP
ADP
GTP
ATP
Mitochondria Cellular Power Plant
• Unique Characteristics:
– Contains its own DNA (maternal lineage only)
– Double membrane
• The inner memrane is heavily folded into "cristae"
• The gel-like fluid "matrix" contains enzymes for production of adenosine
triphosphate (ATP)
• Energy conversion
– C-H bonds of substrate (food) is converted to high energy phosphate
bonds through the citric acid cycle (also called the Kreb or
tricarboxylic acid cycle).
• Hydrogen atoms carried by nicotinamide adeninje dinucleotide (NAD)
and flavine adenine dinucleotide (FAD)
*importance of niacin and riboflavin
• Electrons carried through a very oerdered series of reactions to incoporate
energy into usable form (ATP)
•Oxygen is the final electron acceptor; combines with H+ to form water
•Carbon combines with oxygen to form CO2
Organization of the cell
• Membranes: Structurally define cells, nucleus, and organelles.
– Phospholipids
Phsopholipids are amphipathic
• Phospholipids are polar, having hydrophobic "tails" made of lipids, and
hydrophilc "head" groups
– Phosphatidylcholine: head is choline (lecithins)
Phospholipids are amphipathic
• Phospholipids are polar, having hydrophobic "tails" made of lipids, and
hydrophilc "head" groups
– Phosphatidylcholine: head is choline (lecithins)
– Phosphatidylethanolamine: head is ethanolamine
– Phosphatidylinositol: well…you get the idea
– The hydrophobic "tail" is composed of varying phospholipids, a fatty acid
esterified to glycerol or (serine [sphingomyelin])
Because of this polar nature, phospholipids self-assemble in aqueous solutions to
form bilayers.
micelle
Organization of the cell
•Membranes: Structurally define cells, nucleus, and organelles.
– Phospholipids- primary “building block” of the membrane
• Fluid; mobile
• Individual phospholipids remain in a singel monolayer
• Provide some substrate for cellular signalling
– Cholesterol
• stiffens membranes
• Can move in any dimension through membrane
– Glycolipids: lipid/sugar moiety
– Proteins
– Glycoprotein: protein/sugar moiety
DNA
RNA
Protein
RNA
• Messenger RNA (mRNA) - long, single nucleotide
strands that resemble half of a DNA molecule and carry the
"message" containing instructions for protein synthesis
from the DNA in the nucleus to the ribosomes in the
cytoplasm.
• Transfer RNA (tRNA) - small, between 70 and 80
nucleotides, cloverleaf-shaped molecules that “transfer”
amino acid molecules to the mRNA.
Protein synthesis
involves two major phases:
Transcription - complementary mRNA is made at the DNA gene.
Three-base sequences, or triplets, on the DNA specify a particular
amino acid. The corresponding three-base sequences on mRNA
are called codons. The form is different, but the information is the
same.
Translation – The mRNA is "decoded" to assemble proteins in a
ribosome using tRNA. The language of nucleic acids (base
sequence) is "translated" into the language of proteins (amino acid
sequence). There are four basic steps:
• Messanger RNA from the nucleus attaches to a ribosome in the cytoplasm.
• Transfer RNA transports an amino acid to the mRNA strand and
recognizes a mRNA codon calling for its amino acid by binding its
anticodon to the codon.
• The ribosome moves the mRNA strand along as each codon is read
sequentially.
• As each amino acid is bound to the next by a peptide bond, its tRNA is
released. The polypeptide chain is released when the termination (stop)
codon is read.
5’
Endoplasmic Reticulum (ER)
Cellular manufacturing facilities
• Major site of protein synthesis
– ribosomes begin the polypeptide synthesis process with a segment that
binds to a signal-recognition protein (SRP) in the cytoplasm.
– SRP associates with a transmembrane receptor, or docking protein, on the
“rough” ER. [NOTE: the SRP inhibits peptide synthesis until it can dock].
– Synthesis and translocation of the polypeptide into the ER occur
simultaneously.
Endoplasmic Reticulum (ER)
Cellular manufacturing facilities
•Major site of protein synthesis
–ribosomes begin the polypeptide synthesis process with a segment that
binds to a signal-recognition protein (SRP) in the cytoplasm.
–SRP associates with a transmembrane receptor, or docking protein, on the
“rough” ER. [NOTE: the SRP inhibits peptide synthesis until it can dock].
–Synthesis and translocation of the polypeptide into the ER occur
simultaneously.
• Secretory proteins:
– translocated freely into interior of the ER
– Move to "smooth" ER secrion for encapsulation
– Vesicle "pinched off" for secretion, or further processing at Golgi complex
Endoplasmic Reticulum (ER)
Cellular manufacturing facilities
• Major site of protein synthesis
– ribosomes begin the polypeptide synthesis process with a segment that
binds to a signal-recognition protein (SRP) in the cytoplasm.
– SRP associates with a transmembrane receptor, or docking protein, on the
“rough” ER. [NOTE: the SRP inhibits peptide synthesis until it can dock].
– Synthesis and translocation of the polypeptide into the ER occur
simultaneously.
• Secretory proteins:
– translocated freely into interior of the ER
– Move to "smooth" ER secrion for encapsulation
– Vesicle "pinched off" for secretion, or further processing at Golgi complex
•Transmembrane proteins:
–Translated into the ER membrane
–Membrane and protein is later incorporated into plasma membrane or
membrane of other organelles
Endoplasmic Reticulum (ER)
Cellular manufacturing facilities
• Major site of protein synthesis
– ribosomes begin the polypeptide synthesis process with a segment that
binds to a signal-recognition protein (SRP) in the cytoplasm.
– SRP associates with a transmembrane receptor, or docking protein, on the
“rough” ER. [NOTE: the SRP inhibits peptide synthesis until it can dock].
– Synthesis and translocation of the polypeptide into the ER occur
simultaneously.
• Other functions: "smooth" ER contains enzymes for
– Lipid synthesis: lipid and steroidal hormone synthesis
– Detoxifying: endogenous and exogenous toxic substances (esp. liver)
– Calcium storage (muscle; sarcoplasmic reticulum)
Golgi Complex
The devil is in the details
Transport vesicles
from smooth ER
Fuse with golgi
stack, and
proteins undergo
refinement
Vesicles
containing final
products are
released from
distal stack
Golgi Complex
Cellular refining facilities
• Post-translational Modification
–
–
–
–
Glycosylation (oligosaccharide )
Disulfide bonds
Folding
Quaternary structure:
• Sorting and directing
Vesicular Transport
Sorting and Directing
(Example: proteins for secretion)
• Directed binding of proteins to specific markers
– Sorting signal: on the protein to be secreted
– Recognition marker: on golgi-binds the sorting signal
triskelions
Recognition marker
Sorting signal
Vesicular Transport
Sorting and Directing
(Example: proteins for secretion)
• Directed binding of proteins to specific markers
– Sorting signal: on the protein to be secreted
– Recognition marker: on golgi-binds the sorting signal
• Triskelions (clathrin) or adaptins in cytosol form a "coating" that
also causes bulging to form the vesicle.
• Coating may (or not) shed, exposing the V-snare
Coating may be shed to expose V-snares
V-snare docks at T-snare on target membrane
Protein released beyond the membrane
Triskelions form coat and cause bulging
Triskelions form coat and cause bulging
Triskelion (clathrin) self-assembly
Lysosomes
Cellular cleanup crew
• Membrane-enclosed sacs of hydrolytic enzymes
– Remove cellular debris
– Destroy invading pathogens
Vaults
Ribonucleoprotein complexes that contain
untranslated RNA.
Function speculated: storage, transport, or
removal?
Elevated in multi-drug resistance in
cancers.
Cytosol
(cytoplasm and friends)
• Ribosomal protein synthesis
• Intermediate metabolism and storage: degradation, synthesis, or
transformation of small organic molecules for fuel.
– Metabolism
• Glycolysis - breakdown of simple sugars (esp. glucose) for oxidative
metabolism. Yields small amount of energy.
• Process fatty and amino acids for entry into TCA cycle
– Storage
• Fat droplets (esp adipose cells)
• Glycogen
• Ultrastructure - the cytoskeleton
– Microtubules: at 22 nm, the largest of the cytoskeletal structures;
composed of tubulin
• Architecture: needed to maintain asymetry (Ex. Axons) or act as scaffolding
during development
• Motion
– Transport of materials (vesicles, etc.)
– Movement
– Mitosis
_
end
+
end
Cytosol
(cytoplasm and friends)
• Ribosomal protein synthesis
• Intermediate metabolism and storage: degradation, synthesis, or
transformation of small organic molecules for fuel.
– Metabolism
• Glycolysis - breakdown of simple sugars (esp. glucose) for oxidative
metabolism. Yields small amount of energy.
• Process fatty and amino acids for entry into TCA cycle
– Storage
• Fat droplets (esp adipose cells)
• Glycogen
• Ultrastructure - the cytoskeleton
– Microtubules: at 22 nm, the largest of the cytoskeletal structures;
composed of tubulin
• Architecture: needed to maintain asymetry (Ex. Axons) or act as
scaffolding during development
• Motion
via dynein and kinesin
Cytosol
(cytoplasm and friends)
• Ribosomal protein synthesis
• Intermediate metabolism and storage: degradation, synthesis, or
transformation of small organic molecules for fuel.
• Ultrastructure - the cytoskeleton
– Microtubules: at 22 nm, the largest of the cytoskeletal structures; composed of
tubulin
– Microfilaments: at 6 nm, the smallest visible with standard EM;
composed of actin (G-form), which forms twisted strands (F-form).
• Architechture: cell section stiffeners
– Microvilli: increased surface areas in repeating pattern
– Stress fibers: interconnect membrane sections forming support
•
Movement
– Commonly with myosin molecules
» Myofilaments
» Transport
– Amoeboid motion: cyclic assembly/dissembly of actin from sol to gel state
Cytosol
(cytoplasm and friends)
• Ribosomal protein synthesis
• Intermediate metabolism and storage: degradation, synthesis, or
transformation of small organic molecules for fuel.
• Ultrastructure - the cytoskeleton
– Microtubules: at 22 nm, the largest of the cytoskeletal structures; composed of
tubulin
– Microfilaments: at 6 nm, the smallest visible with standard EM; composed of
actin (G-form), which forms twisted strands (F-form).
– Intermediate filaments: stable protein strands, 7-10 nm; Provide a stable
framework within the cell.
"free" ribosomes
ER
Plasma membrane
microtubule
microfilament
Intermediate filaments