Pathways Flashcards
1
Q
LDL
A
- Lipoprotein molecules sequester cholesterol and transport it around
- Clathrin-coated pit forms
- LDL binds to receptor in coated pit
- Clathrin-coated vesicle forms and pinches off
- Sorting via vesicle trafficking to lysosome
- LDL released from vesicle
- Receptors are recycled back
2
Q
Insulin Secretion
A
- Glucose enters cell through GLUT 2 transporter
- Converted to glucose-6-phosphate
- Undergoes glycolysis, TCA cycle, ETC/oxphos
- ATP produced by ETC inhibits K+ channel, depolarizes cell
- Ca2+ voltage-dependent channel opens and Ca2+ flows in
- Ca2+ stimulates fusion of insulin vesicles to cell membrane and exocytosis/secretion of insulin to ECF
- Biphasic release (rapid, then slow)
3
Q
CFTR gating
A
- R domain phosphorylated by cAMP-dependent protein kinase A
- ATP binds to nucleotide binding domain 1 (NBD1)
- Hydrolysis of ATP by NBD1 opens channel transiently
- PKA phosphorylates more sites on R domain
- NBD2 binds ATP, stabilizes open channel
- ATP hydrolysis at NBD2 closes channel
- R domain dephosphorylation closes channel
4
Q
ATP transfer from matrix to cytoplasm
A
- Proton gradient generated by pumping protons (from oxidation of NADH and FADH2) from matrix into intermembrane space during ETC
- Proton motive force causes H+ to move down gradient through ATP synthase, driving synthesis of ATP
- ATP is transported from matrix to intermembrane space via voltage gradient-drive ATP/ADP exchange protein in inner mitochondrial membrane
- ATP leaves mitochondria via voltage-dependent anion channels in outer membrane to cytoplasm (ADP produced in cytoplasm enters mitochondria for recharging)
5
Q
Ischemic injury –> altered bioenergetics (mitochondria)
A
Ischemia = no O2 –> aerobic respiration (TCA cycle) doesn’t occur) –> ATP decreases –> anaerobic respiration increases –> lactate increases
6
Q
Altered ionic balance (mitochondria)
A
- No ATP causes dysfunction of NaK pump –> K+ decreases in cell, Na+ increases in cell –> H2O enters cell
- Buildup of lactate causes H+ increase –> NaH antiport pump increases Na+ inside cell as H+ flow out –> H2O enters cell
- Increase in H2O and osmotic pressure –> organelles swell –> cellular vacuolization –> hydropic degeneration
- NaCa pump (antiport w/ Na+ gradient) –> with no ATP –> can’t pump Ca2+ out –> Ca2+ activates intracellular enzymes –> causes decrease in ATP –> decrease in phospholipids –> protein disruption –> DNA damage
7
Q
Glutathione
A
- GGT transfers gamma-glutamyl function group from GSH to AA outside cell
- AA moves across cell membrane
- gamma-Glutamyl cyclotransferase catalyzes release of AA, free amino group of Glu cyclizes to 5-oxoproline lactam
- 5-oxoprolinase converts 5-oxoproline to glutamate
- gamma-Glutamylcystein synthetase combines glutamate and cysteine to form gamma-Glutamylcysteine (RATE LIMITING STEP)
- Glutathione synthetase combines gamma-Glutamylcysteine and glycine to form GSH
8
Q
Production of urea from AA
A
- Transamination (transfer of alpha-amino group from alpha-AA to alpha-keto acid to form new alpha-AA and new alpha-keto acid): alpha-ketoglutarate accepts alpha-amino group to form glutamate)
- Transamination: glutamate transfers alpha-amino group to oxaloacetate to form aspartate (enters urea cycle)
- Oxidative deamination: glutamate loses alpha-amino group to form alpha-ketoglutarate –> that NH4+ + CO2 –> carbamoyl-P (enters urea cycle)
9
Q
Urea cycle
A
- High Arg levels initiate cycle in mitochondrial matrix
- Glu + Acetyl CoA –> N-acetyl-Glu (via N-acetyl-Glu synthetase, which is allosterically activated by Arg)
- NH4+ + CO2 + 2ATP –> carbamoyl-P + 2ADP + Pi (via carbamoyl phosphate synthetase CPS I, which is activated by N-acetyl-Glu)
- Carbomoyl P + L-Ornithine –> L-Citrulline + Pi (via ornithine transcarbamolyase OTC)
- L-Citrulline moves to cytosol
- L-Asparatate enters cytosol from TCA cycle
- L-Citrulline + L-Aspartate (donates N for formatin of urea) + ATP –> Argininosuccinate + AMP + PPi (via argininosuccinate synthetase AS)
- Argininosuccinate –> Fumarate + L-Arginine (via argininosuccinate lysase AL)
- L-Arginine + H2O –> L-Ornithine + urea (via arginase)
- L-Ornithine moves back into matrix
- Fumarate enters TCA cycle
10
Q
Glycogen synthesis
A
In hepatocyte:
- Glucose undergoes glycolysis in cytoplasm, TCA cycle in mitochondria, which produces citrate
- Citrate inhibits PFK (key regulatory enzyme in glycolysis)
- Extra citrate used to synthesize fatty acids, secreted out of cells in VLDL to adipocytes.
- Inhibition of glycolysis causes glycogen formation to be stimulated (regulated by GSK- glycogen sythase kinase, which inhibits glycogen synthase)
- Glucose (increased in blood now) binds to insulin receptor
- Insulin pathway inhibits GSK, which removes glycogen synthase inhibition –> promotes production and storage of glycogen
11
Q
Rhodopsin-mediated action
A
- Rods of eye contain opsin protein
- Opsin + 11-cis-retinaldehyde (form of vit A) –> rhodopsin
- Rhodopsin receives light energy during vision in dim light –> light converts cis-retinal to trans-retinal, which is released along w/ opsin
- Electrical energy produced by rxn is sent from retina to brain via optic nerve, communication of visual images
- Process repeats
12
Q
Ethanol metabolism
A
Follows zero-order kinetics (water soluble, stays in blood and muscle)
In liver:
1. Ethanol to acetaldehyde + NADH (via ADH) in cytosol
2. Acetaldehyde to acetic acid + NADH (via aldehyde dehydrogenase ALDH) in mitochondria – vit C and thiamine absorb free radicals
3. Acetic acid to acetyl-CoA in muscle
4. Acetyl-CoA enters normal TCA cycle
- Increase ratio NADH/NAD+ –> stops TCA cycle (don’t need energy b/c of NADH)
- pushes pyruvate –> lactate –> lactate acidemia –> inhibits uric acid secretion in urine
- stops gluconeogenesis (by depletion of oxaloacetate)–> don’t produce glucose –> hypoglycemia
- pushes Acetyl-CoA to ketone bodies –> ketoacidosis
- accumulate triglycerides and inhibit B-ox of FA –> hyperlipidemia
*Induces CYP450 to metabolize other drugs (like tylenol)
