Editing Pyruvate dehydrogenase complex (section)

=== Pyruvate dehydrogenase (E1) ===
{{Main|Pyruvate dehydrogenase}}
Initially, [[pyruvate]] and [[thiamine|thiamine pyrophosphate]] (TPP or [[thiamine|vitamin B<sub>1</sub>]]) are bound by [[pyruvate dehydrogenase]] subunits.<ref name=":0" /> The [[thiazole|thiazolium]] ring of TPP is in a [[zwitterion]]ic form, and the [[anion]]ic C2 carbon performs a nucleophilic attack on the C2 (ketone) carbonyl of pyruvate. The resulting intermediate undergoes [[decarboxylation]] to produce an acyl anion equivalent (see [[cyanohydrin]] or aldehyde-dithiane [[umpolung]] chemistry, as well as [[benzoin condensation]]). This anion attacks S1 of an oxidized lipoate species that is attached to a [[lysine]] residue. In a ring-opening S<sub>N</sub>2-like mechanism, S2 is displaced as a sulfide or sulfhydryl moiety. Subsequent collapse of the tetrahedral intermediate ejects thiazole, releasing the TPP cofactor and generating a thioacetate on S1 of lipoate. The E1-catalyzed process is the rate-limiting step of the whole pyruvate dehydrogenase complex.