Subject pyruvate dehydrogenase

The most important factor in the regulation of the cycle is the NADH/NAD ratio. In addition to pyruvate dehydrogenase (PDH) and oxoglu-tarate dehydrogenase (ODH see p. 134), citrate synthase and isodtrate dehydrogenase are also inhibited by NAD deficiency or an excess of NADH+HT With the exception of isocitrate dehydrogenase, these enzymes are also subject to product inhibition by acetyl-CoA, suc-cinyl-CoA, or citrate. 

Experiments with rats have shown that the branched-chain a-keto acid dehydrogenase complex is regulated by covalent modification in response to the content of branched-chain amino acids in the diet. With little or no excess dietary intake of branched-chain amino acids, the enzyme complex is phosphorylated and thereby inactivated by a protein kinase. Addition of excess branched-chain amino acids to the diet results in dephosphoiylation and consequent activation of the enzyme. Recall that the pyruvate dehydrogenase complex is subject to similar regulation by phosphorylation and dephosphorylation (p. 621). 

Regulation of Pyruvate Dehydrogenase Activity Pyruvate dehydrogenase is the key enzyme that commits pyruvate (and hence the products of carbohydrate metabolism) to complete oxidation (via the tricarboxyUc acid cycle) or lipogenesis. It is subject to regulation by both product inhibition and a phosphorylation/dephosphorylation mechanism. Acetyl CoA and NADH are both inhibitors, competing with coenzyme A and NAD+. 

The role of thirimin diphosphate in pyruvate dehydrogenase means that, in deficiency, there is imprdred conversion of pyruvate to acetyl CoA, and hence impaired entry of pyruvate into the citric acid cycle. Especially in subjects on a relatively high carbohydrate diet, this results in increased plasma concentrations of lactate and pyruvate, which may lead to life -threatening lactic acidosis. 

Pyruvate dehydrogenase a Multienzyme complex (see) responsible for the formation of acetyl-CoA from pyruvate, one of the central metabolic reactions (see Pyruvate, Acetyl-coenzyme A). It is subject to three types of control l.The enzyme complex is inhibited by acetyl-CoA and NADH the transace-tylase is inhibited by acetyl-CoA, and NADH inhibits the dihydrolipoyl dehydrogenase. These inhibitions are reversed by CoA and NAD, respectively. 2. Enzyme activity is influenced by the energy state of the cell the complex is inhibited by GTP and activated by AMP 3. The complex is inhibited when a specific serine residue in the pyruvate decarboxylase is phos-phorylated by ATP This phosphorylation is inhibited by pyruvate and ADP The complex is reactivated by... 

The El component of pyruvate dehydrogenase complexes is subject to allosteric regulation by pyruvate and acetyl-CoA, and it is additionally regulated by phosphorylation in mammals. 

Pyruvate dehydrogenase (PDH). PDH utilizes thiamine as a coenzyme. A follow-up study of subjects with reduced PDH activity reported that reduced PDH activity may lead to a future onset of diabetes. 

The reactions catalysed by the pyruvate dehydrogenase complex (PDH) irreversibly commit the carbon skeleton of glucose to ultimate oxidation by the reactions of the citrate cycle either directly or via the formation of fatty acids. It is not surprising therefore to find that such an important reaction is under close control. Thus it is subject to ... 

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