Question

Can someone explain the role of the three subunits of the pyruvate dehydrogenase complex? Like how those subunits help with the complex turnign pyruvate into acetyl coA? Also why and how does the pyruvate move from cytoplasm to mitochondria? Also why does the Krebs cycle not accept pyruvate? Why does it need to be turned into acetyl coA first?

Answer 1

Role of three subunits in Pyruvate dehygrogenase Complex and formation of Pyruvate to Acetyl CoA:

Acety CoA is formed from pyruvate through a process of oxidative decarboxylation by Pyruvate dehydrogenase which is a multienzyme complex  with 3 enzymes :

• Pyruvate dehydrogenase(E1 subunit)
• Dihydrolipoyl transacetylase(E2 subunit)
• Dihydrolipoyl dehydrogenase (E3 subunit)

E1 Subunit: Decarboxylases pyruvate with intermediate formation of hydroxy ethyl TPP.(thiamine pyrophosphate). The hydroxyethyl group is transferred to the next subunit where the reaction occurs by attack of hydroxy ethyl group carbanion on lipoamide disulphide with elimination of acetyl dihydrolipoamide and regenerate active E1.

E2  Subunit: On being received hydroxyethyl group and being formed as Acetyl dihydrolipo amide E2, it catalyses the transfer of acetyl group to CoA, yielding Acetyl CoA and dihydrolipoamide - E2. This is a transesterification reaction.

E3  Subunit: Reoxidises dihydrolipoamide, completing the catalytic cycle of E2.This is done by reactive disulfide group and tightly bound FAD.

Transport of Pyruvate to mitochondria:

The transport of pyruvate from cytosol into the mitochondria is cordinated by the Pyruvate Translocase via a H+ which is a transportation protein. Pyruvate translocase helps in transporting pyruvate in a symport fashion with a proton, by consuming energy. Upon entry to the mitochondria, the pyruvate is decarboxylated, producing acetyl-CoA.

Why pyruvate to Acetyl CoA:

Acetyl CoA acts as a fuel for the citric acid cycle in the next stage of cellular respiration. The addition of CoA helps to activate the acetyl group, helps it to undergo the necessary reactions to enter the citric acid cycle.