Pyrimidines Pyruvate dehydrogenase

Pyridoicairunie phosphate (PMP, 541,544 P doKic acid excreticrn test, 548-549 Pyrimidine, biosynthesis, 500-502,504 Pyroglutamate, 69, 70 Pyrrole, chemical slruetUK, 753 pyruvate, 159, 228 Pyruvate cartKwylase, 703,802 Pyruvate dehydrogenase, 159, 228, 231, 466,491... 

Vitamin Bi is an essential co-factor for several enzymes of carbohydrate metabolism such as transketolase, pyruvate dehydrogenase (PDH), pyruvate decarboxylase and a-ketoglutarate dehydrogenase. To become the active co-factor thiamin pyrophosphate (TPP), thiamin has to be salvaged by thiamin pyrophosphokinase or synthesized de novo. In Escherichia coli and Saccharomyces cerevisiae thiamin biosynthesis proceeds via two branches that have to be combined. In the pyrimidine branch, 4-amino-5-hydroxymethy-2-methylpyrimidine (PIMP) is phosphorylated to 4-amino-2-methyl-5-hydroxymethyl pyrimidine diphosphate (PIMP-PP) by the enzyme HMP/HMP-P kinase (ThiD) however, the step can also be catalyzed by pyridoxine kinase (PdxK), an enzyme also responsible for the activation of vitamin B6 (see below). The second precursor of thiamin biosynthesis, 5-(2-hydroxyethyl)-4-methylthiazole (THZ), is activated by THZ kinase (ThiM) to 4-methyl-5-(2-phosphoethyl)-thiazole (THZ-P), and then the thia-zole and pyrimidine moieties, HMP-PP and THZ-P, are combined to form thiamin phosphate (ThiP) by thiamin phosphate synthase (ThiE). The final step, pyrophosphorylation, yields TPP and is carried out by thiamin pyrophosphorylase (TPK). 

Pyrimidine nucleoside radiolabeled 1262 Pyrococcus furiosus 709 Pyrogen test 1565 Pyroline-5-carboxylate 975 Pyrosequencing 87 Pyrrhocoricin 486 Pyruvate dehydrogenase 1075 Pyruvate-formate lyase 1075... 

Figure 4.2 Reactions of pyruvate-processing enzymes pyruvate decarboxylase (PDC), p5Tuvate oxidase (POX), pyruvate ferredoxin oxidoreductase (PFOR) and pyruvate dehydrogenase (PDH). Their reactions diverge after the decarboxylation step. Pyr and PP represent 2,5-dimethyl-4-amino-pyrimidine and the ethyl diphosphate tail, respectively.

As shown in Fig. 7, the first step involved in the decarboxylation of an alpha-keto acid by thiamine pyrophosphate is the addition of the carbonyl by the carbanion nucleophile, followed by decarboxylation of the acid. As reviewed by Jencks (1975), investigations of the role of thiamine pyrophosphate analogs in the pyruvate dehydrogenase-catalyzed decarboxylation of pyruvate have provided evidence for rate enhancement by a desolvation effect. This effect comes about because of the removal of both the carboxylate group of the substrate and the cationic nitrogen of the coenzyme from an aqueous environment to the hydrophobic active site of the enzyme. The bulky and apparently chemically nonfunctional pyrophosphate and pyrimidine moieties of the... 

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