【多选题】How does the pyruvate dehydrogenase (PDH) complex work?
A.
The PDH complex is composed of multiple copies of three enzymes: pyruvate dehydrogenase, E 1 (with its bound cofactor TPP); dihydrolipoyltransacetylase, E 2 (with its covalently bound lipoyl group); and dihydrolipoyl dehydrogenase, E 3 (with its cofactors FAD and NAD).
B.
E1 catalyzes first the decarboxylation of pyruvate, producing hydroxyethyl-TPP, and then the oxidation of the hydroxyethyl group to an acetyl group. The electrons from this oxidation reduce the disulfide of lipoate bound to E 2 , and the acetyl group is transferred into thioester linkage with one –SH group of reduced lipoate.
C.
E 2 catalyzes the transfer of the acetyl group to coenzyme A, forming acetyl-Co E 3 catalyzes the regeneration of the disulfide (oxidized) form of lipoate; electrons pass first to FAD, then to NAD + .
D.
The long lipoyllysyl arm swings from the active site of E 1 to E 2 to E 3 , tethering the intermediates to the enzyme complex to allow substrate channeling.