Pyruvate dehydrogenase cofactors

Pyruvate Dehydrogenase Cofactors and Mechanism Describe the role of each cofactor involved in the reaction catalyzed by the pyruvate dehydrogenase complex. 

The conversion occurs through a multistep sequence of reactions catalyzed by a complex of enzymes and cofactors called the pyruvate dehydrogenase complex. The process occurs in three stages, each catalyzed by one of the enzymes in the complex, as outlined in Figure 29.11 on page 1152. Acetyl CoA, the ultimate product, then acts as fuel for the final stage of catabolism, the citric acid cycle. All the steps have laboratory analogies. 

Pyruvate is oxidized to acetyl-GoA by a multienzyme complex, pyruvate dehydrogenase, that is dependent on the vitamin cofactor thiamin diphosphate. 

A somewhat more trivial thing to remember about the HMP pathway is that this is one of the places you ve seen the vitamin thiamin pyrophosphate. This cofactor is necessary for the transketolase reaction that is in the middle of the HMP pathway. The transketolase reaction converts two C-5 sugars to a C-7 and a C-3. The other place you ve seen thiamin pyrophosphate as a cofactor is in the pyruvate dehydrogenase and a-ketoglutarate dehydrogenase reactions. 

Cofactors and coenzymes used by pyruvate dehydrogenase include ... 

Figure 3.4 Structure of two prosthetic groups (a) biotin (b) lipoate. Biotin functions as a carboxyl group carrier, e.g. in acetyl-CoA carboxylase. Lipoate is presented in its oxidised form (-S-S-). It is a cofactor for pyruvate dehydrogenase and oxoglu-tarate dehydrogenase.

The PDH complex is composed of multiple copies of three enzymes pyruvate dehydrogenase, Ei (with its bound cofactor TPP) dihydrolipoyl transacetylase, E2 (with its covalently bound lipoyl group) and dihydrolipoyl dehydrogenase, E3 (with its cofactors FAD and NAD). 

A. Structure of thiamine and its cofactor form, thiamine pyrophosphate. B. Structure of intermediate formed in the reaction catalyzed by pyruvate dehydrogenase. C. Structure of intermediate formed in the reaction catalyzed by a-keto-glutarate dehydrogenase. 

Answer Thiamine is essential for the formation of thiamine pyrophosphate (TPP), one of the cofactors in the pyruvate dehydrogenase reaction. Without TPP, the pyruvate generated by glycolysis accumulates in cells and enters the blood. 

Answer The pyruvate dehydrogenase complex can be thought of as performing five enzymatic reactions. The first three (see Fig. 16-6) catalyze the oxidation of pyruvate to acetyl-CoA and reduction of the enzyme. The last two reactions are essential to reoxidize the reduced enzyme, reducing NAD+ to NADH + H+. The moiety on the enzyme that is oxidized/reduced is the lipoamide cofactor. 

Understand the physiologic importance and mode of synthesis of glycerol-3-phosphate, 2,3-diphosphoglycerate, and acetyl-CoA understand the mechanism of action and regulation of pyruvate dehydrogenase with all the cofactors involved. 

Pyruvate produced by the glycolytic pathway may be transported into the mitochondria (via an antiport with OH"), where it is converted to acetyl-CoA by the action of the enzyme complex pyruvate dehydrogenase. The pertinent enzyme activities are pyruvate dehydrogenase (PD), lipoic acid acetyltransferase, and dihydrolipoic acid dehydrogenase. In addition, several cofactors are utilized thiamine pyrophosphate (TPP), lipoic acid, NAD+, Co A, and FAD. Only Co A and NAD+ are used in stoichiometric amounts, whereas the others are required in catalytic amounts. Arsenite and Hg2+ are inhibitors of this system. The overall reaction sequence may be represented by Figure 18.5. The NADH generated may enter the oxidative phosphorylation pathway to generate three ATP molecules per NADH molecule reduced. The reaction is practically irreversible its AGq = -9.4 kcal/mol. 

In addition to its cofactor role, thiamin diphosphate, together with calcium or other divalent cations, activates pyruvate dehydrogenase by binding to a regulatory site and reducing the for pyruvate (Czerniecki and Czygier, 2001). 

Flow of carbon atoms. What is the fate of the radioactive label when each of the following compounds is added to a cell extract containing the enzymes and cofactors of the glycolytic pathway, the citric acid cycle, and the pyruvate dehydrogenase complex (The label is printed in red.)... 

Vitamins are required in the diet for groMh, maintenance, and reproduction. These qualities are shared by other nutrients, such as the amino adds and the minerals- Why are amino acids and minerals not called vitamins The vitamins share a family of characteristics. They are organic compounds required in the diet in only smaii amounts They are not catabolized to satisfy part of the energy requirement and are not used for structural purposes. Many vitamins are used as cofactors for enzymes. Pyruvate dehydrogenase is one striking example. This enzj me uses five cofactors, where four of these cofactors are derived from vitamins-... 

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