A. Cellular Physiology
a. Describe the cell membrane and its properties.
b. Describe the functions of mitochondria, endoplasmic reticulum and other
organelles.
Plasma membrane semipermeable lipid bilayer 7.5 nm thick
phospholipids, cholesterol
proteins
structural
pumps
active ion/molecule transport
channels
receptors
clathrins cluster to endocytose bound ligands
insulin & other peptides, lipoproteins, viruses
enzymes
intercellular connections
tight junctions
desmosomes
belt with bands of filaments containing actin
spot central stratum of filaments
hemi- epithelial cell to connective tissue
gap junctions
connexons allow molecules up to 800 d to pass
rise in Ca2+ closes
Cytoplasm
Golgi complex
vesicles → secretory granules
Endoplasmic reticulum (rough and smooth)
RNA → protein transcription in ribosomes
glycosylation of proteins
formation of vesicles and lysosomes
Lipid droplets
Lysosomes
merge with (auto-)phagocytic vacuoles and release
ribonuclease, deoxy~, phosphatase, glycosidases, arylsulfatases,
collagenase, cathespins
release of enzymes into the cell causes damage in vit A toxicity, ?gout
enzyme defects cause lysosomal storage disorders
Mitochondria
separate DNA (female lineage)
outer and inner membrane with cristae
operate the citric acid cycle “cellular respiration” → ATP
Secretory granules
Centrioles
2 cylinders and right angles near nucleus
made of 9x3 microtubules
form the mitotic spindle in cell division
Microfilaments
long fibres of actin 4-6 nm diameter operate microvilli and attach to belt
desmosomes
Microtubules
25 nm diameter tubules made of α and ß tubulin (5 nm thick)
maintain cell shape, constantly form and disassemble
Cilia
Cellular metabolism
1.A.1
James Mitchell (December 24, 2003)
contain 9x2 +2 microtubules and basal granule of 9x3 microtubules
Nucleus
Chromosomes
2x22 + sex chomosomes
composed of DNA (2.5x109 base pairs), histones
contain genes, promoters, enhancers, junk
Nucleolus
site of RNA synthesis by transcription
Envelope with perinuclear cisterns
very permeable to allow RNA out
c. Explain mechanisms of transport of substances across cell membranes.
Diffusion
rate determined by (Fick’s Law)
chemical gradient
electrical gradient
cross-sectional area of boundary
thickness of boundary
Donnan Effect
non-diffusible ions affect diffusion of other ions.
ratio of diffusible cations between compartments equals inverse ratio of
diffusible anions.
Solvent drag
unimportant effect. Solvent bulk flow carries solute.
Filtration
rate determined by
pressure gradient
surface area of boundary
permeability of boundary
Osmosis
solvent molecules cross a membrane to a region of higher activity of a non-diffusible
solute.
P=nRT/V
Carrier-mediated transport
facilitated diffusion
transport usually of large, non-ionized molecules down a
concentration/electrical gradient across the cell membrane via membrane
proteins. e.g. glucose uptake
active transport
transport of molecules or ions against of concentration or
electrical gradient, usually mediated by ATPase proteins in
the cell membrane e.g. Na+-K+ ATPase, Ca2+ ATPase, H+-K+
β
ATPase
ATP
α
transports 3 Na+ out of and 2 K+ into cells
inhibitied by cardiac glycosides
composed of 2 α (95 kd binds ATP and digoxin) and 2 ß
3Na+
(40 kd glycoprotein) subunits.
Na+ binding is associated with phosphorylation
generates a membrane potential
rate-limited by intracellular Na+
responsible for most of BMR
symport
transport coupled to an electrical or chemical gradient
e.g. Na+-glucose exchange inmucosal cells, Ca2+-Na+ exchange in cardiac muscle
Transport of large molecules
Cellular metabolism
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James Mitchell (December 24, 2003)
proteins and hormones are commonly transported by exo- or endo-cytosis
d. Explain the Gibbs-Donnan Effect.
e. Outline the role of cellular receptors and the function of secondary messengers
within the cell.
f. Outline the sources of energy available to cells through metabolic processes.
Sources of energy
High energy phosphate compounds: ATP, phosphorylcreatine, GTP, CTP, UTP, ITP
Thioesters of Coenzyme-A: acetyl-CoA (≡ 1 ATP)
Reduced coenzymes: NADH, NADPH (≡ 3 ATP) via flavoprotein-cytochrome system
H2 donor, NAD+, FAD, Co Q, Cyt B, Cyt c1, Cyt c, Cyt a, Cyt a3, O2.
Carbohydrates
Dietary sugars → di- and mono-saccharides in gut → circulating glucose, fructose and
galactose (→ glucose) → intracellular glucose ↔ glucose 6-PO4 (- ATP)
Embden-Meyerhof pathway
glycogen ↔ n glucose 1-PO4 ↔ glucose 6-PO4 ↔ fructose 6-PO4 ↔ fructose 1,6
diPO4 (-ATP) ↔ dihydroxyacetone PO4 (↔ glycerol) + phosphoglyceraldehyde
→ → pyruvate (+ 2 ATP, 1 NADH)
Hexose-monophosphate shunt
glucose 6-PO4 ↔ 6-phosphogluconic acid → pentoses → fructose 6-PO4 or
phosphoglyceraldehyde
Τricarboxylic acid cycle
pyruvate + CoA → acetyl-CoA (+ 2H + CO2) … + oxaloacetic acid → citric acid
→ → → oxaloacetic acid + 8H + 2CO2
net yield = 10H → 5NADH → 15ATP
Aerobic glycolysis proceeds via the Embden-Meyerhof pathway and TCAC for 38 ATP
per glucose molecule.
Anaerobic metabolism relies on the Embden-Meyerhof pathway only, yielding 4 ATP
per glucose molecule less one for the phosphorylation of fructose 6-PO4 and one more
if glucose 6-PO4 is generated from circulating glucose. The generation of NAD+
required is via the conversion of pyruvic acid to lactic acid, generating an “oxygen
debt”.
Control of glucose metabolism is regulated by
β adrenergic receptors which promote glycolysis via cAMP, protein kinase,
phosphorylase kinase and phosphorylase a as well as inhibition of glycogen
synthase when it is phosphorylated. This causes a rise in blood glucose and
lactate largely arising from glycolysis in liver and muscle respectively.
α adrenergic receptors which activate phosphorylase kinase via intracellular
Ca2+.
Glucagon which stimulates phosphorylase in liver only, causing a rise in blood
glucose without lactate.
Insulin
g. Explain the ways in which cells use energy for the various cellular processes.
h. Describe the composition of intracellular fluid and its regulation including the
role of the sodium-potassium pump.
ECF (20%) ≈ estuarine water
Interstitial fluid (15%)
Na+ 143 mEq/l
K+
4
Ca2+ 5
Cellular metabolism
ClHCO3HPO421.A.3
117 mEq/l
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James Mitchell (December 24, 2003)
Mg2+ 3
SO421
org acid 6
protein 2
plus H2CO3 and non-electolytes
Plasma (5%)
Na+ 152 mEq/l
K+
5
2+
Ca
5
Mg2+ 3
Cl113 mEq/l
HCO327
2HPO4
2
SO421
org acid 6
protein 16
plus H2CO3 and non-electolytes
Transcellular fluid (small)
CSF, aqueous humor, GIT contents etc.
ICF (40%)
Very rough concentrations:
Na+ 14 mEq/l
PO42113 mEq/l
+
K
157
HCO310
2+
Mg 26
protein 74
plus H2CO3 and non-electolytes
i. Describe the role of G-proteins.
j. Describe the general response to injury.
Cellular metabolism
1.A.4
James Mitchell (December 24, 2003)