Chapter 3 - Victoria College

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CHAPTER 3

The Cellular Level of Organization

INTRODUCTION

• A cell = basic living, structural, & functional unit of body

• Cytology = study of cell structure

• Cell physiology = study of cell function

• Generalized view of cell = composite of many different cells

• No single cell includes all of the features seen in the generalized cell.

PARTS of a CELL

• Cell can be divided into three principal parts:

– Plasma (cell) membrane (PM)

– Cytoplasm

• Cytosol

• Organelles (except for the nucleus)

– Nucleus

THE PLASMA MEMBRANE

• Flexible, sturdy barrier surrounding cytoplasm of cell

• Fluid mosaic model (Figure 3.2)

– “Proteins in a sea of lipids”

– Lipid bilayer (amphipathic)

• two back-to-back layers of PL molecules

– FA tail region = NONpolar (hydrophobic)

– PO

4

-3 head region = polar (hydrophilic)

• cholesterol

• glycolipids

– glyco = “sugar”

– extracellular face only

Arrangement of Membrane Proteins

• Integral proteins

– amphipathic

– anchored w/in membrane

• Peripheral proteins

– associated w/ head of PL or w/ integral protein

– can be removed from membrane

– glycoproteins

• CHO groups protrude into ECF

• glycocalyx

Functions of Membrane Proteins

• Ion channels (integral)

• Transporters (integral

• Receptors (integral)

• Enzymes (integral or peripheral)

• Cell identity marker (glycoprotein)

• Linkers (integral and peripheral)

Membrane Fluidity

• “Mobility with structure”

– movement w/in bilayer

– no flip-flop

• Dependent upon:

– # of double bonds in fatty acid tails of lipids

– amount of cholesterol present

• stabilizes membrane

• reduces fluidity @ normal body temp.

• Allows self-repair of lipid bilayer

• Enables many cellular processes

– assembly of membrane proteins

– cell movement, growth, etc.

Membrane Permeability

• Selective permeability

– Permeable to small, nonpolar, uncharged molecules

– Permeable to water

– Impermeable to ions & charged or polar molecules

• Increased by transmembrane proteins

• Macromolecules must cross PM via vesicular transport.

Gradients Across PM

• Difference in concentration of a chemical or electrical charge between opposite sides of PM

– Concentration gradient

– Electrical gradient

– Electrochemical gradient

• Allow for movement of substances across PM

– “downhill” movement

• Oxygen & Na + more concentrated outside cell

• CO

2

& K + more concentrated inside cell

TRANSPORT ACROSS PM

• “Downhill” movement is passive

– Diffusion thru lipid bilayer

– Diffusion thru ion channels

– Facilitated diffusion

• Requires transporter (usually a protein)

• “Uphill” movement is “active”

– Requires cellular energy in form of ATP

• Substances can also enter or leave cell thru vesicle transport

Principles of Diffusion

Diffusion = random mixing of particles that occurs in a solution as a result of the kinetic energy of the particles

• Occurs down concentration gradient

• Equilibrium eventually achieved

• Diffusion rate influenced by :

– Steepness of the concentration gradient

– Temperature

– Size or mass of the diffusing substance

– Surface area

– Diffusion distance

Diffusion Through Lipid Bilayer

Nonpolar, hydrophobic molecules diffuse freely

– respiratory gases

– lipids

– small alcohols

– ammonia

• Important for gas exchange, absorption of some nutrients, & excretion of some wastes

Diffusion Thru Membrane Channels

• Most are ion channels

– small, inorganic (hydrophilic) ions

• Ion channels are selective

– gated or open all the time

– slower than free diffusion because site specific

Osmosis

• Water molecules penetrate membrane via diffusion

– through lipid bilayer

– through aquaporins

• transmembrane proteins that function as water channels

• Water moves from an area of lower solute concentration to an area of higher solute concentration.

• Occurs only when membrane is permeable to water but not to certain solutes

Osmotic Pressure

Force exerted on membrane by impermeable solute

Proportional to [solute] that cannot cross membrane

Tonicity

• Measure of solution’s ability to change volume of cells by altering their water concentration

Isotonic solution

– [solute] is same on both sides of PM

– RBCs maintain normal shape (Fig. 3.7a)

Hypotonic solution

– [solute] in sol’n lower than inside cell (cytosol)

– Water flows into cell to equalize [solute]

– RBCs undergo hemolysis (Fig. 3.7b)

Hypertonic solution

– [solute] in sol’n higher than inside cell (cytosol)

– Water flows out of cell to equalize [solute]

– RBCs undergo crenation (Fig. 3.7c)

Facilitated Diffusion

• Transport of highly charged or polar solutes across PM

• Solute binds to specific transporter

– Transporter undergoes a conformational change

– Solute carried from one side of PM to other

• Saturable process

– Transport maximum

– Rate of facilitated diffusion dependent upon:

• steepness of concentration gradient

• # of transporter proteins available

• Transport of glucose, urea, fructose, galactose, & some vitamins

• **PASSIVE process!!

Facilitated Diffusion of Glucose

• Glucose binds transport protein

• Transport protein Δ shape

• Glc moves across PM ( down concentration gradient)

• Kinase enzyme reduces

[glc] inside cell

– glc-6-P unusable by cell

• Transporter proteins always bring glucose into cell

Active Transport

• Moves solutes AGAINST concentration gradient

• Requires energy

– ATP (primary)

– Ion concentration gradient

(secondary)

• Saturable process

• Ex: Na + /K + pump (Fig 3.8)

Primary Active Transport

• Na + /K + pump most prevalent (Figure 3.8)

– Energy derived from ATP hydrolysis

– Maintains low [Na+] and high [K+] in cytosol

• 3 Na + bind transporter (intracellular side of

PM)

• ATP hydrolysis causes conformational change & release of Na + to ECF

• 2 K + bind & cause release of P i to cytosol

• Conformational change & 2 K + released in cytosol

Secondary Active Transport

• Energy stored in Na + or H + concentration gradient drives other substances against own gradients

• Indirect use of ATP

• Digitalis slows Na + /Ca +2 ion antiporters

– allows more Ca +2 to stay inside heart muscle cells

• increases force of contraction  strengthens heartbeat

Transport in Vesicles

• Invaginations of PM enclose substances & transport into or out of cell

– Endocytosis = bringing something into cell

– Exocytosis = release of something from cell

• Vesicular transport is an active process

Vesicular Transport--Endocytosis

• Receptor-mediated endocytosis = selective uptake of large molecules/particles by cells

– Ex: internalization of LDL particles

• Phagocytosis = macrophages & neutrophils engulf large particles

– Particle binds to receptor protein on PM & is surrounded by pseudopods

– Disposal of microbes, old cells, etc.

• Pinocytosis (bulk-phase endocytosis) = cell drinking

– No receptor proteins

Vesicular Transport--Exocytosis

• Exocytosis

– Vesicle formation inside cell

– Vesicle fuses w/ cell membrane

– Vesicle products released from cell

• digestive enzymes, hormones, NT, wastes

– Replace/recycle cell membrane lost during endocytosis

CYTOPLASM

Cytosol = the semifluid portion of cytoplasm that contains inclusions and dissolved solutes

Organelles = specialized structures that perform specific functions in cellular growth, maintenance, and repro.

The Cytoskeleton

• Network of protein filaments throughout cytoplasm

• Functions:

– Structural framework of cell

– Cell/organelle movement

• Microfilaments

• Intermediate filaments

• Microtubules

Centrosomes

• Contain centrioles: paired cylinders arranged at right angles to one another

• Organize microtubules in interphase cells

• Organize mitotic spindle during cell division

Cilia and Flagella

• Hair-like structures important for cellular movement

• Cilia

– numerous, short, projections extending from cell surface

– move materials across surface of cell

• Flagella

– much longer than cilia

– usually move an entire cell

Ribosomes

• Composed of ribosomal RNA & protein

• Sites of protein synthesis

• Free ribosomes are loose in cytosol

– synthesize proteins found inside the cell

• Membrane-bound ribosomes

– attached to endoplasmic reticulum or nuclear membrane

– synthesize proteins needed for plasma membrane or for export

• Inside mitochondria, ribosomes synthesize mitochondrial proteins

Ribosomal Subunits

• Large + small subunits

– made in the nucleolus

– assembled in cytoplasm

Endoplasmic Reticulum (ER)

• Network of membranes that form flattened sacs

• Store, package & transport newly synthesized molecules

• Detoxification (SER in liver)

• Releases Ca +2 ions in muscle contraction

(sarcoplasmic reticulum)

• Fatty acid & steroid synthesis (liver SER)

Endoplasmic Reticulum

• Rough ER (RER)

– Extension of nuclear membrane

– Ribosomes on outer surface

– Secretory, membrane & organelle proteins

• Smooth ER (SER)

– Extension of rough ER

– No ribosomes

– Detox, FA/steroid synth., Ca release in muscle

Golgi Complex

• Flattened membranous sacs that process, sort, and deliver proteins & lipids to other parts of cell

• Different enzymes allow for modification/packaging of various proteins

Lysosomes

• Membrane-enclosed vesicles formed from Golgi

• Numerous digestive enzymes

• Functions

– digest foreign substances

– autophagy

• recycles own organelles

– autolysis

• tissue damage after death

• Tay-Sachs disease

– caused by absence of single lysosomal enzyme

– glycolipids accumulate & interfere w/ nerve function

Peroxisomes

• Similar in structure to, but smaller than lysosomes

• Contain oxygen-requiring enzymes

– Oxidases  oxidize various organic compounds

– Catalases  break down H

2

O

2

• Important in normal catabolism of amino acids and fatty acids

• Oxidize toxic substances

– Alcohols

– Formaldehyde

Proteosomes

• Destroy unneeded, damaged, or faulty proteins

• Proteases cut proteins into small peptides

• Faulty proteosomes are possible factor in some degenerative diseases

– Fail to break down abnormal proteins

– Parkinson’s & Alzheimers

Mitochondria

• Cellular powerhouses

– Site of ATP production

• Catabolism of nutrients

• O

2 required 

– Located where O

2

ATP is used aerobic enters cell or

• Bound by double membrane

• Cristae

– Folds in inner membrane

– Enormous surface area for reactions of cellular respiration

• Matrix

– Central cavity

– Site of metabolic reactions

NUCLEUS

• Directs cellular activity

• Controls cell structure

• Most body cells have one nucleus (mononucleate)

– RBCs are anucleate

– Skeletal muscle fibers are multinucleate

• Parts of nucleus include

– nuclear envelope which is perforated by nuclear pores

– nucleolus

– genetic material (DNA)

• Contains cell’s hereditary units (genes) which are arranged on chromosomes

NUCLEUS

• 46 (23 pair) human chromosomes

– Genes found on chromosomes

– Genes direct synthesis of specific protein

• Non-dividing cells contain nuclear chromatin

– Loosely packed DNA, RNA & protein complex

– Histones = proteins that direct DNA folding

• Dividing cells contain chromosomes

– Tightly packed DNA

– DNA copied itself before condensing into chromatids

Chromosomes

• Each chromosome = long molecule of DNA coiled together with several proteins

• Human somatic cells have

46 chromosomes (23 pairs)

• Various levels of DNA packing represented by nucleosomes, chromatin fibers, loops, chromatids, & chromosomes

PROTEIN SYNTHESIS

• Genes expressed as proteins

• Proteins determine phys/chem characteristics of cells

• DNA is template for protein synthesis

• Transcription (txp)

– Genetic info in DNA copied onto single-stranded RNA

• Three types of RNA

– Messenger RNA (mRNA)

– Ribosomal RNA (rRNA)

– Transfer RNA (tRNA)

• Translation

– mRNA read by ribosomes

– “Message” translated into a. a. sequence of protein

Transcription

• DNA sense strand = template for creation of mRNA strand

• RNA polymerase (RNApol) attaches to promoter sequence

& initiates txp

• RNApol reaches terminator sequence & detaches  txp stops

• Genes contain XS information

– Pre-mRNA contains introns that are cut out by enzymes

– Exons: regions of mRNA code for segments of protein

• “gene splicing”

• snRNPs

– Thus 1 gene can yield several proteins

Protein Synthesis

• Instructions for making specific proteins found in DNA (your genes)

– transcribe that information onto mRNA molecule

• each sequence of 3 nucleotides in DNA = base triplet

• each triplet transcribed as 3 RNA nucleotides (codon)

– translate “message” into sequence of amino acids in order to build protein

• each codon must be matched by anticodon found on the tRNA carrying a specific amino acid

Translation

• Sequence of nucleotides (ntd) on mRNA is “read” by rRNA to construct a protein

• Small ribosomal subunit is attachment site for mRNA

• Large ribosomal subunit has 2 tRNA binding sites

– P site: where tRNA-a.a. attaches to mRNA

– A site: holds incoming tRNA-a.a.

• Specific tRNA molecules carry specific amino acids

• 3-nucleotide sequences = codons

– AUG is ALWAYS the start codon

– tRNA anticodon = UAC & it codes for methionine

• Anticodons on tRNA match specific codons on mRNA so proper a.a can be strung together to create protein

Translation

Sequence is as follows:

• Initiator tRNA

• Start codon on mRNA

• Functional ribosome formed

– initiator tRNA fits into P site on rRNA

• Anticodon of tRNA match codons of mRNA

• Stop codon on mRNA

CELL DIVISION

• Process by which cells reproduce themselves

– nuclear division (mitosis and meiosis)

– cytoplasmic division (cytokinesis)

Somatic cell division: reproduction of any body cell except sex cells

– nuclear division (mitosis)

– cytokinesis

– distribute two sets of chromosomes —one set into each of two separate nuclei

Reproductive cell division: production of gametes

– nuclear division (meiosis)

– cytokinesis

Chromosome Number

• Human somatic cells contain 46 chromosomes (23 pairs)

Homologous chromosomes (homologs) = two chromosomes that make up a chromosome pair

• A cell with a full set of chromosomes is diploid (2N)

• A cell with only one chromosome from each pair is haploid (N)

– Mitosis yields diploid cells

– Meiosis yields haploid cells

Cell Cycle in Somatic Cells

• Orderly sequence of events by which cell duplicates its contents and divides in two

• Consists of interphase and mitotic phase (Figure 3.28)

Interphase

• Cell carries on every life process except division

• Doubling of DNA and centrosome

• Three subphases of interphase:

– G1 = replication of cytosolic components (G

0 non-dividing cell) if

– S = replication of chromosomes

• “commitment” stage  cell will divide

– G2 = cytoplasmic growth

Replication of Chromosomes During Interphase

• Doubling of genetic material during interphase (S phase)

• DNA molecules unzip (histones)

• Mirror copy formed along each old strand

• Nitrogenous bases pair with complementary base

• 2 complete, identical DNA molecules formed

Interphase

• Cell shows distinct nucleus

• DNA present as chromatin

• Nuclear membrane in tact

MITOSIS: Prophase

• Chromatin condenses & shortens into chromosomes

– Identical chromatids joined by centromere

• Centrosomes migrate to opposite poles

• Disintegration of nuclear membrane/nucleolus

MITOSIS: Metaphase

• Centromeres line up at exact center of mitotic spindle,

(metaphase plate or equator)

MITOSIS: Anaphase

• Splitting & separation of centromeres

• Chromatids from each pair move toward opposite poles of cell

– appear V-shaped as they are pulled by centromeres

• Late anaphase: formation of cleavage furrow begins

MITOSIS: Telophase

• Begins when chromatid movement stops

• Chromosomes at opposite poles revert to chromatin form

• New nuclear envelope/nucleoli form

• Mitotic spindle breaks up

CYTOPLASMIC DIVISION: Cytokinesis

• Division of parent cell’s cytoplasm and organelles

• Begins late anaphase/ early telophase

• Following completion of cytokinesis, interphase begins

• Cancer = uncontrolled cell division  some anticancer drugs stop this by inhibiting spindle formation

Control of Cell Destiny

• Three possible destinies of a cell

– Live & function without dividing

– Growth & division

– Death

• CDKs crucial for regulation of cell growth/division

– Regulated by cyclins

• Apoptosis = programmed cell death

– Triggered intra- or extracellularly by “cell-suicide” gene

– Removes unneeded/unwanted cells

• Necrosis = pathological (abnormal) cell death

– Stimulates inflammatory response

• Tumor-suppressor genes normally inhibit cell division

– Ex: p53 arrests cells in G

1 colon cancers

 damage leads to breast or

Reproductive Cell Division: Meiosis

Results in production of haploid (n) cells containing only 23 chromosomes

Occurs in two successive stages:

Meiosis I

Meiosis II

CELLS AND AGING

• Aging = normal, progressive alteration of body’s homeostatic adaptive responses

• Physiological signs of aging:

– Gradual deterioration in function

– Decline in responsiveness

– Net decrease in number of cells in body & increased dysfunction of remaining cells

• Extracellular components of tissues (e.g., collagen fibers and elastin) also change with age

• Theories of aging:

– genetically programmed cessation of cell division, glc addition to proteins, free radical rxn, & excessive immune responses

DISORDERS: HOMEOSTATIC IMBALANCES

Cancer = group of diseases characterized by uncontrolled cell proliferation

• Cells that divide without control develop into a tumor or neoplasm.

• Cancerous neoplasm = malignant tumor or malignancy

– Capable of metastasizing

• spread of cancerous cells to other parts of the body

• A benign tumor = noncancerous growth

Cancer = Uncontrolled cell division

• Hyperplasia = increased number of cell divisions

– benign tumor does not metastasize (spread)

– malignant tumors spread because detach from tumor & enter blood/lymph

• Causes

– exposure to carcinogens, x-rays, viruses

– every cell has genes that regulate growth & development

– mutations in those genes due to radiation or chemical agents causes excess production of growth factors

• Carcinogenesis

– multistep process that takes years (and requires many different mutations) to occur

Types of Cancer

Carcinomas arise from epithelial cells.

Melanomas = cancerous growths of melanocytes

Sarcomas arise from muscle cells or connective tissues.

Leukemia = cancer of blood-forming organs

Lymphoma = cancer of lymphatic tissue

Growth and Spread of Cancer

• Cancer cells divide rapidly and continuously.

– Trigger angiogenesis

Metastasis occurs when cancer cells leave site of origin

& travel to other tissues/organs

Causes of Cancer

• Normal counterparts of oncogenes = proto-oncogenes

– found in every cell

– cells fcn normally until a malignant Δ occurs

• Anti-oncogenes or tumor-suppressing genes

– may produce proteins that normally oppose the action of an oncogene or inhibit cell division

• Carcinogenesis = multistep process involving mutation of oncogenes & anti-oncogenes

– 10 distinct mutations may have to accumulate in a cell before it becomes cancerous

Treatment of Cancer

• Difficult because it is not a single disease & because all cells in a tumor do not behave in same way

• Various treatments include

– Surgery

– Chemotherapy

– Radiation therapy

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