Pyruvate Dehydrogenase Complex

E2

dihydrolipoamide transacetylase

E3

dihydrolipoamid dehydrogenase

Step 1 in E1

Uses TPP to catalyze the decarboxylation of an alpha ketoacid/pyruvate and form a hydroxyethyl-TPP intermediate

Step 2 in E1

Oxidation of hydroxyethyl-TPP and transfer to lipoamid to form acetyllipoamide-final E1 product

Step 3 in E2

E2 catalyzes the transfer of the acetyl group from acetyllipomamide to Coenzyme A (leaving reduced lipoamide) forming Acetyl CoA

Step 4 in E3

E3 oxidation of lipoamide to to reoxidize/regenerate lipoamide by reducing FAD → FADH2

Step 5 in E3

transfer of the 2e- from a tightly bound FADH2 to transiently bound NAD+ generating FAD and NADH

TPP

decarboxylation of pyruvate located in E1

Lipoic acid (lipoamide)

acyl transfer and e- carrier (part of E2)

CoA

acceptor of acetyl group from acetyllipoamide forming acetyl CoA

FAD

accepts e- from dihydrolipoamide in E3

NAD+

final e- acceptor in E3

Pyruvate Dehydrogenase Kinase

activators and inactivators

turns off PDH

Activators: NADH, AcetylCoA

Inactivators: Pyruvate

Pyruvate Dehydrogenase Kinase phosphorylation or dephosphorylation inactivates?

phosphorylation of E1

Pyruvate Dehydrogenase Phosphatase activators and inhibitors

activates PDH complex

Activators: Ca2+, Insulin signaling via cascade

Inactivators: high NADH and high Acetyl CoA

PD Phosphatase phosphorylation or dephosphorylation inactivates

dephosphorylation of E1