Pyruvate dehydrogenase

From Free net encyclopedia

Template:Not verified Pyruvate dehydrogenase (Template:EC number) is an allosteric enzyme that transforms pyruvate into acetyl-CoA by a process called oxidative decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration. Oxidative decarboxylation is also known as the "pyruvate dehydrogenase reaction" because it is catalyzed by this enzyme.

[edit]

Structure & function

Pyruvate dehydrogenase is a large complex composed of multiple copies of 3 subunits: 24 copies of pyruvate decarboxylase (E1), 24 copies of dihydrolipoyl transacetylase (E2) and 12 copies of dihydrolipoyl dehydrogenase (E3). The three subunit enzymes are present in different numbers in different species, so the size of pyruvate dehydrogenase differs.

Thiamine pyrophosphate (TPP) is bound to E1, and catalyses the decarboxylation of pyruvate. The TPP remains bound to the acetate through a thioester bond. This bond brings the acetate in proximity to an oxidized lipoyllysine, to which it becomes esterified. The acetate is trans-esterified from the sulfide of the lipoyl 'swinging arm' to coenzyme A (CoA), where it forms acetyl-CoA. The reduced lipoyllysine becomes oxidized, reducing the flavin adenine dinucleotide (FAD) that is covalently linked to E3. The FADH then reduces nicotinamide adenine dinucleotide (NAD), returning the pyruvate dehydrogenase complex to is original state. The acetyl-CoA is free to enter the TCA cycle.

The multi-enzyme complex is related (structually and functionally) to the similar oxoglutarate dehydrogenase multi-enzyme complex.

The global reaction catalysed by pyruvate dehydrogenase is:

Pyruvate + Coenzyme A + NAD⁺ ⇒ acetyl-CoA + NADH + H⁺ + CO₂

[edit]

Cofactors

5 different cofactors are required for this complex:

TPP (Thiamine pyrophosphate) - Hydroxyethyl Carrier
CoA (Coenzyme A) - Substituted onto the Acetyl group to form Acetyl-CoA
R-Lipoic acid - Utilized as a Lysine Tether to transport Acetyl group to acitve site for CoA addition
FAD (Flavin Adenine Dinucleotide) - Oxidizing agent to oxidize the lipoyllysine sulfaring to repeat process.
NAD (Nicotinamide adenine dinucleotide)- Oxidizes FADH₂ in order to repeat process. NADH is then used for oxidative phosphorylation or may be used somewhere else in the cytosol.

Multiple copies of each different cofactor may be necessary for proper function of this complex.

[edit]