Lectures 17-18: Regulation of TCA + Ox. phos. Flashcards
5 pathways of carbohydrates from diet
- glycolysis
- gluconeogenesis
- glycogenesis
- glycogenolysis
- pentose phosphate pathway
4 pathways of fats from diet
- b-oxidation
- FA synthesis
- TG synthesis
- Cholesterol synthesis
5 pathways of proteins from diet + 1 extra
- transamination
- urea cycle
- aa catabolism
- aa synthesis
- synthesis of aa derivatives
+ nucleic acid synthesis
what is cellular respiration?
- 3 stages
- process by which pyruvate produced by glycolysis is further oxidized to H2O and CO2 (cells consume O2 and produce CO2)
1. acetyl CoA production/oxidation of fuels to acetyl-CoA
2. acetyl CoA oxidation/oxidation of acetyl groups to Co2 in the citric acid cycle
3. electron transfer chain and oxidative phosphorylation
generally:
- stage 1 of cellular respiration –> 3 things into what? + generates (3)
- stage 2: 1 thing into 2 things + generates (3)
- stage 3: 2 things into 1 thing + generates what?
- aa, fatty acids and glucose –> acetyl-coA
+ generates ATP, NADH and FADH2 - acetyl-coa into NADH and FADH2 through citric acid cycle
+ generates NADH, FADH2 and 1 GTP/ATP - NADH and FADH2 into ATP through respiratory/electron transfer chain
+ generates vast majority of ATP from catabolism
where does each stage of cellular respiration happen?
- glycolysis –> cytoplasm
- TCA cycle –> mitochondrial matrix
- oxidative phosphorylation –>inner mitochondrial membrane
3 sources of acetyl-coa?
- b oxidation of fat
- amino acids (leucine, thronine, etc.)
- glycolysis yields pyruvate
pyruvate is the intermediate that links what 2?
- 2 central catabolic pathways
- glycolysis and TCA cycle
citric acid cycle is a hub of metabolism: with ________ pathways leading in and ________ pathways leading out
- catabolic leading in
- anabolic leading out
3 fates of pyruvate from glycolysis?
- enters mitochondria to be oxidized by citric acid cycle to generate energy
- after its conversion to acetyl-CoA, may be used as starting material for synthesis of FA and sterols
- precursor for synthesis of amino acids
pyruvate to acetyl-coA is what kind of reaction?
- reversible or irreversible?
- explain what happens
- what is generated?
- transfer of e- from _______ to _______ generates __-__ ATP
- oxidative decarboxylation
- irreversible
- carboxyl group is removed from pyruvate, forming CO2 and 2 remaining carbons becomes acetyl group of acetyl-CoA
- NADH generated –> enters respiratory chain as e- donor
- NADH to oxygen generates 2-5 ATP
what enzyme complex catalyzes pyruvate to acetyl-coa?
- which 5 cofactors are needed? which one not derived from vitamins?
- pyruvate dehydrogenase complex (E1 + E2 + E3)
- CoA-SH, NAD+, lipoate, TPP, FAD
- lipate not derived from vitamins
pyruvate dehydrogenase (PDH) complex:
- cluster of multiple copies of what?
- describe E1, E2 and E3 –> name + cofactors
- multiple copies of 3 enzymes (60 copies in bovine PDC)
- E1 = pyruvate dehydrogenase –> bound cofactor TPP
- E2 = dihydrolipoyl transacetylase –> covalently bound lipoyl group of lipoate
- E3 = dihydrolipoyl dehydrogenase –> cofactors FAD and NAD
pyruvate to acetyl-coa
- do intermediates leave the enzyme surface?
- what is that called?
- which cofactors remain bound to their enzyme?
- no! never leave enzyme surface
- substrate channeling
- thiamine pyrophosphate (TPP), lipoate and FAD
which steps of pyruvate to acetyl-coa catalyzed by which enzyme?
E1 –> step 1 and 2:
1. pyruvate + TPP –> release CO2
2. hydroxyethyl TPP tnrasfers 2e- to acyl lipoyllysine
E2 –> step 3:
3. acyl lipoylysine reduced + CoA-SH replaces SH group to form acetyl-CoA, releasing reduced lipoyllysine
E3 –> steps 4 and 5
4. FAD to FADH2 (reduced)
5. FADH2 transfers e- to NAD+ to form NADH + H+
citric acid cycle:
- how many intermediates?
- how many enzymes/steps?
- 5 general steps
- 9 intermediates
- 8 enzymes/steps
1. acetyl-coA donates 2C to oxaloacetate (4C) forming citrate (6C)
2. citrate transformed to isocitrate (6C)
3. isocitrate dehydrogenated with loss of Co2 to form a-ketoglutarate (5C)
4. a-ketoglutarate loses CO2 and yields 4C succinate
5. succinate converted in 3 steps into 4C oxaloacetate –> ready for another cycle
4 net by-products of citric acid cycle
- 2 CO2 (isocitrate to a-ketoglutarate + a ketoglutarate to succinyl coA)
- 3 NADH (same reactions that produce CO2 + malate to oxaloacetate)
- 1 FADH2 (succinate to fumarate)
- 1 ATP/GTP (succinyl-CoA to succinate)
do carbons of acetyl-coa contribute to CO2 production?
No
TCA cycle can serve both ________ and ________ pathways –> is __________
- catabolic and anabolic
- is amphibolic
reactions that replenish intermediates are called what?
- 4 examples
- anaplerotic
1. pyruvate + HCO3 + ATP –> oxaloacetate (through pyruvate carboxylase)
2. phosphoenolpyruvate + CO2 + GDP –> oxaloacetate + GTP (PEP carboxykinase)
3. phosphoenolpyruvate + HCO3 –> oxaloacetate (PEP carboxylase)
4. pyruvate + HCO3- + NADPH –> malate + NADP+ (malic enzyme)
regulation of TCA cycle:
- enzymes of which reactions are regulated?
- cycle is activated by what?
- cycle is inhibited by what?
- PDH is phorphorylated on which enzyme = __________
- what does succinyl-CoA inhibit?
- what activates TCA cycle?
- of irreversible reactions
- substrate (acetyl-CoA)
- inhibited by product accumulation
- on E1 enzyme = inactivation of complex
- succinyl-CoA inhibits citrate synthase (acetyl-Coa –> citrate) and a-ketoglutarate dehydrogenase complex (a-ketoglutarate –> succinyl-coa) to regulate a-ketoglutarate for aa metabolism
- Ca2+