Pyruvate Dehydrogenase

goal of pyruvate dehydrogenase reaction

convert pyruvate to acetyl CoA so it can enter the TCA cycle

what happens to pyruvate in the reaction

one carbon is removed from the molecule as CO2 (oxidative decarboxylation), and the remaining 2-carbon molecule is attached to coenzyme A (CoA)

overall reaction and the enzyme that catalyzes it

pyruvate + CoA + NAD+ → acetyl CoA + NADH + H+ (redox); pyruvate dehydrogenase (PDH)

why PDH is considered a committed step

the reaction is irreversible and the glucose molecule is now committed to oxidation

core components of PDH

E1, E2, and E3

E1 actual name

pyruvate dehydrogenase

E1 role in PDH

oxidative decarboxylation (removing the CO2 from pyruvate)

E2 actual name

dihydrolipoyl transacetylase

E2 role in PDH

corms high energy thioester bond between the 2-carbon molecule and CoA to make acetyl CoA

E3 actual name

dihydrolipoyl dehydrogenase

E3 role in PDH

reduce NAD+ to NADH

cofactor used by E1

thiamine pyrophosphate (TPP)

cofactors used by E2

lipoamide and CoA

cofactors used by E3

FAD and NAD+

TPP role in PDH

stabilizes the 2-carbon molecule after CO2 removal

lipoamide role in PDH

carries the 2-carbon molecule between E1 and E2 active sites

CoA role in PDH

accepts the acetyl group (2-carbon molecule) to form acetyl CoA

FAD and NAD+ role in PDH

FAD accepts electrons from lipoamide and transfers them to NAD+ to form NADH and regenerate oxidized lipoamide

methods of PDH regulation

allosteric regulation (based on energy status) and covalent modifications (state of phosphorylation)

energy signals that inhibit PDH

high energy (NADH and acetyl CoA)

energy signals that activate PDH

low energy (ADP and pyruvate)

PDH is ______ by phosphorylation

inactivated

PDH is _____ by dephosphorylation

activated

net yield of pyruvate dehydrogenase reaction per glucose

2 acetyl CoA, 2 NADH, 2 CO2