Pyruvate dehydrogenase is a complex enzyme: utilizes four different coenzymes; has a mol. wt. = 4.6 megadaltons; consists of a total of 60 polypeptide chains (three different types: 24, 24, and 12 of each)

Analogy of TCA cycle, electron transport, and oxidative phosphorylation to steam electrical generator:

Furnace TCA cycle
Heat NADH
Steam H+
Spinning turbine Oxidative Phos.
Electricity ATP

Reactions:
A. Condensation of Acetyl-CoA and oxaloacetate (aldol condensation)

B. Isomerization reactions, moving the hydroxyl group of citrate into a more desirable position. This is an example of chiral synthesis from prochiral substrate.

C. Two oxidative decarboxylations

D. Regeneration reactions

Regulation at pyruvate dehydrogenase:

inhibitors = AcCoA, NADH, ATP

pyruvate --------> acetyl-CoA

activators = AMP

In addition, in eukaryotic cells, this enzyme can be phosphorylated at a serine (inactive); dephosphorylation yields the active form of the enzyme

PDH phosphatase (activated by Mg2+ and Ca2+)

PDH-P (inactive)

PDH (active)

PDH kinase (activated by NADH, AcCoA)