Pyruvate dehydrogenase Flashcards
What is the equation of the reaction catalysed by pyruvate dehydrogenase?
Pyruvate + CoA + NAD+ —> Acetyl CoA + NADH + CO2
What is the structure of three enzymes that comprise pyruvate dehydrogenase?
E2 forms the transacetylase core, E1, and E3 surround the E2 core
What are the free and bound cofactors of the three PDH enzymes?
E1 = bound TPP cofactor, no free E2 = bound lipoamide cofactor, free Coenzyme A E3 = bound FAD cofactor, free NAD+
What is the reaction carried out by E1 of PDH?
E1 carries out decarboxylation of pyruvate through TPP carbanion attacking the carbonyl group of pyruvate to rom hydroxyethyl-TPP
What are the 2 reactions carried out by E2 of PDH?
1) trans acetylation of hydroxyethyl-TPP: the hydroxyethyl group is transferred to lipoamide and oxidised to form acetyl group (the lipoamide is reduced at the S-S bond) to form acetyllipoamide
2) formation of acetyl CoA: acetyl group transferred to CoA to form acetyl CoA and dihydrolipoamide arm of E2
What are the reactions carried out by E3 of PDH?
1) FAD is reduced as 2 electrons and two H+ are transferred from dihydrolipoamide, restoring the lipoamide arm of E2 and producing FADH2
2) the 2 electrons from FADH2 are used to reduce NAD+ to NADH
What is the importance of the multienzyme complex structure of PDH? (three things)
1) coordinated catalysis
2) reduce side reactions as intermediates are channelled between active sites by lipoamide arm
3) maximise efficiency and rate as less diffusion between active sites.
What is the main regulatory control of PDH?
reversible phosphorylation at 3 Ser residues on E1 by PDH kinase and PDH phosphatase
Phosphorylated PDH = inactive
Dephosphorylated PDH = active
What regulates PDH kinase?
Positive = NADH, ATP, Acetyl CoA (inactivates PDH) Negative = Pyruvate, NAD+, CoA, ADP/AMP (allows PDH activity)
What regulates PDH phosphatase?
increase in intracellular calcium ions increases PDH phosphatase to increase PDH activity = important in muscles
