What other cofactors or cosubstrates does the pyruvate dehydrogenase complex require to function?

Pyruvate dehydrogenase (PDH) is a very high molecular weight mitochondrial multienzyme complex.It includes three types of enzymes that need the participation of five coenzymes to develop their activity, three of them catalytic cofactors (TPP, lipoamide, FAD) and two stoichiometric (NAD and CoA). Two enzymes involved in regulating its activity are also part of the enzyme complex.

Explanation:

PDH is a multienzyme complex formed by multiple copies of three catalytic proteins (E1, E2 and E3) and other structural and regulatory (phosphatase, kinase). It requires, in turn, different coenzymes (thiamine, lipoic acid) for its proper functioning. Given its enormous importance at a key point in energy production, it is highly regulated. E1 depends on thiamine pyrophosphate and catalyzes 2 stages: 1) decarboxylation of pyruvate, forming a hydroxyethyl-thiamine-diphosphate intermediate; 2) reductive acetylation of the lipoyl group, covalently linked (amide) to E2. E2 catalyzes the transfer of the acetyl group to CoA (3). E3 regenerates the oxidized lipoyl, transferring its electrons first to FAD and then to NAD.