Pyruvate Dehydrogenase Flashcards
What are the three main stages involved in the pyruvate dehydrogenase mechanism?
. Decarboxylation of pyruvate
- E1
- Thiamine pyrophosphate (TPP) converts pyruvate to hydroxyethyl residue, with CO2 produced as by-product
. Formation of acetyl CoA
- E2
- Lipoamide converts hydroxyethyl to acetate, then transfers acetate to CoA to produce acetyl CoA
. Regeneration of oxidised lipoamide
- E3
- FADH2 converts NAD to NADH
Write the word equation for the reaction that is catalysed by PDH.
Pyruvate + CoA + NAD → Acetyl CoA + CO2 + NADH
What is the importance of PDH in the TCA cycle?
. Commits pyruvate to the TCA cycle because pyruvate is converted to acetyl CoA by PDH, but acetyl CoA can’t be converted back to pyruvate (irreversible)
. Controls entry of glucose to TCA cycle (rate-limiting step)
Describe the size and structure of PDH.
. Large (4-10 million Dalton’s)
. Multi-subunit- 3 enzyme activities and 5 coenzymes
. 3 enzyme activities (E1, E2, E3)
- E2 is innermost, then E3, then E1 is outermost
. 5 coenzymes (TPP, lipoamide, CoA, NAD, FAD)
What is the importance of vitamin B in the action of PDH?
The coenzymes of PDH are derived from vitamin B, so deficiency in vitamin B means that the coenzymes won’t function effectively and so PDH can’t catalyse the conversion of pyruvate to acetyl CoA.
Give the active and inactive forms of PDH.
. Phosphorylated PDH is inactive
. Dephosphorylated PDH is active
How is PDH activated?
. Dephosphorylated by phosphatase
. Activation of PDH triggered by insulin and calcium ions
How is PDH deactivated?
. Phosphorylated by kinase
. Deactivation of PDH triggered by ATP, NADH, acetyl CoA
What is Beri-beri?
Deficiency of thiamine in diet leads to damage to the peripheral nervous system and weakened muscle → CV disorders
Why is mercury and arsenite a problem with PDH?
Binds to groups on E2 and causes CNS pathologies
