Write out the steps in the pyruvate dehydrogenase reaction and explain the roles
ID: 142902 • Letter: W
Question
Write out the steps in the pyruvate dehydrogenase reaction and explain the roles of thiamine pyrophosphate, lipoic acid/lipoamide, and FAD in this multienzyme reaction Write out the steps in the pyruvate dehydrogenase reaction and explain the roles of thiamine pyrophosphate, lipoic acid/lipoamide, and FAD in this multienzyme reaction Write out the steps in the pyruvate dehydrogenase reaction and explain the roles of thiamine pyrophosphate, lipoic acid/lipoamide, and FAD in this multienzyme reactionExplanation / Answer
Pyruvate dehydrogenase reaction is also known as pyruvate decarboxylation complex in which conversion of pyruvate to acetyl coA occurs by a process of decarboxylation. Pyruvate decarboxylation complex is also known as pyruvate dehydrogenase reaction because it involves the oxidation of pyruvate.
Pyruvate dehydrogenase reaction (PDH) reaction occurs in 3 steps that are catalysed by 3 enzymes and coenzymes of it.
This reaction is multienzyme complex containing pyruvate dehydrogenase along with coenzyme Thiamine pyrophosphate(TPP), Dihydrolipoamide acetyltransferase along with coenzyme Lipoamide, coenzyme A and dihydrolipoamide dehydrogenase along with coenzyme FAD and NAD+
1) Decarboxylation of pyruvate: Pyruvate and thiamine pyrophosphate(TPP) is bound by pyruvate dehydrogenase. TPP form a carbanion and it is a strong nucleophiles so it can play role in decarboxylation of pyruvate.
The TPP attack keto group of pyruvate which leads to covalent intermediate from which carbon dioxide is released. This intermediate located in the hydroxyethyl group is another cabanion which is again resonanse stabilised by TPP and is then ready for release of acetyl CoA.
2) Release of acetyl Co A:
The carbanion on hydroxyethyl group attack the disulphide bond of lipoamide and now the entire substrate is carried by lipoamide and the TPP is cleaved out from the substrate which is then transferred to coenzyme A by dihydrolipoamide acetyltransferase. Thus acetyl co A is formed and lipoamide is reduced to dihydrolipoamide in the process.
3) Reoxidation of dihydrolipoamide:
It is again oxidised by dihydrolipoamide dehydrogenase which transfers hydrogen to NAD+ using FAD as an intermediate carrier.
Roles of TPP, lipoamide and FAD are described below:
TPP- Helps in decarboxylation as it provides a carbanion for nutriophilic attck on substrate.
Lipoamide- Helps in acetyl transfer which transfer substrate to coenzyme A and oxidation reaction in which it retains hydrogen.
FAD- Acts as an oxidising agent which transfer hydrogen from lipoamide to NAD+.
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