PDH & TCA Flashcards
Where does TCA occur?
mitochondrial matrix
function of TCA cycle
oxidation of acetyl CoA & participation in biosynthetic reactions
oxidation of acetyl CoA
metabolism of amino acids, fatty acids, and carbohydrates into CO2 + H2O; accounts for 2/3 of total O2 consumption and ATP production
What biosynthetic reactions does TCA play a part in?
formation of glucose from carbon skeletons of AAs and provides building blocks for heme synthesis
How much ATP can be generated from aerobic glycolysis + TCA?
38
How much ATP can be generated from anaerobic glycolysis?
only 2; no TCA
CoA
carrier of acetyl
acetyl group
CH3-C=O
outer membrane of mitochondria
contains porins that permit free diffusion of small molecules
inner membrane of mitochondria
contains transport proteins that control passage of metabolites such as ATP, ADP, pyruvate, Ca++, and phosphate; also contains coenzymes for ETC
mitochondrial matrix
contains enzymes of TCA cycle; fatty acid oxidation enzymes, ribosomes
pyruvate dehydrogenase complex
multimolecular complex located in mitochondrial matrix
function of PDH complex
converts pyruvate into acetyl-CoA for the TCA cycle
component enzymes of PDH
- pyruvate decarboxylase (E1)
- dihydrolipoyl transacetylase (E2)
- dihydrolipoyl dehydrogenase (E3)
component coenzymes of PDH
- thiamine pyrophosphate
- lipoic acid
- coenzyme A (CoA)
- flavin adenine dinucleotide (FAD)
- nicotinamide adenine dinucleotide (NAD+)
thiamine pyrophosphate (TPP)
E1-bound
lipoic acid
E2-linked
coenzyme A
E2-substrate
FAD
E3-bound
NAD+
E3-substrate
key coenzyme in PDH
thiamine pyrophosphate
Beriberi
clinical manifestation of thiamine deficiency that affects high-energy requiring tissues in the CV and CNS
Beriberi risk factors
diet consisting largely of white rice and alcholism
overall reaction of PDH
pyruvate + CoA + NAD+ –> acetyl-CoA + CO2 + NADH
kinase effect on PDH
phosphorylates PDH, inactivating it
What stimulates kinase to phosphorylate PDH?
increase in acetyl CoA/CoA ration or NADH/NAD+ ratio (more products)
phosphatase effect on PDH
dephosphorylates PDH, activating it
What stimulates phosphatase to dephosphorylate PDH?
increase in ADP/ATP ratio (also inhibits kinase)
TCA cycle
acetyl CoA + oxaloacetate –> citrate –> isocitrate –> alpha-ketoglutarate –> succinyl-CoA –> succinate –> fumarate –> malate –> oxaloacetate
acetyl CoA + oxaloacetate –> citrate
aldol condensation; H2O to CoA
citrate –> isocitrate
isomerization
isocitrate –> alpha-ketoglutarate
oxidation & decarboxylation; NAD+ to NADH + H+ and CO2
alpha-ketoglutarate –> succinyl CoA
oxidation and decarboxylation; NAD+ to NADH + H+ and CO2
succinyl-CoA –> succinate
cleavage of thioester; GDP to GTP and CoA
succinate –> fumarate
oxidation; FAD to FADH2
fumarate –> malate
hydration
TCA cycle overall reaction
acetyl CoA + 3NAD+ + FAD + GDP + Pi + H2O –> 2 CO2 + 3NADH + FADH2 + GTP + 3H+ + CoA
malate –> oxaloacetate
oxidation; NAD+ to NADH + H+
How many electrons transferred during TCA?
4 total; three from reducing NAD+ to NADH and 1 from FAD to FADH2
TCA products
2 CO2, 1 FADH2, 3NADH, and 1GTP
each NADH can produce _ ATP
3; so 9 total each cycle
each FADH2 can produce _ ATP
2
TCA cycle is regulated by _
substrate availability, product inhibition, and competitive feedback inhibition by cycle intermediates
substrate availability _ regulates citrate synthetase
positively; acetyl-CoA & oxaloacetate
product availability _ regulates citrate synthetase
negatively; NADH
cycle intermediates _ TCA cycle
inhibit
positive allosteric regulators of TCA cycle
ADP & Ca++
ADP
levels increase with muscular contraction, biosynthetic reactions; activates isocitrate dehydrogenase
Ca++
activates PDH to make acetyl-CoA; activates isocitrate dehydrogenase & alpha-ketoglutarate dehydrogenase
amphibolic
process that is both catabolic and anabolic –> the TCA cycle
How is TCA cycle amphibolic?
catabolic: acetyl-CoA oxidation for ATP generation
anabolic: biosynthetic pathways use TCA intermediates
malate
transported out of mitochondria and converted to oxaloacetate for gluconeogenesis
citrate
citrate from citrate synthetase is exported to cytosol and converted back to acetyl-CoA for fatty acid and cholesterol biosynthesis
alpha-ketoglutarate
used to make glutamate
succinyl-CoA
starting material for porphyrin (heme) biosynthesis
