Thiamin diphosphate coenzyme function

Why do we need vitamins Early clues came in 1935 when nicotinamide was found in NAD+ by H. von Euler and associates and in NADP+ by Warburg and Christian. Two years later, K. Lohman and P. Schuster isolated pure cocarboxylase, a dialyz-able material required for decarboxylation of pyruvate by an enzyme from yeast. It was shown to be thiamin diphosphate (Fig. 15-3). Most of the water-soluble vitamins are converted into coenzymes or are covalently bound into active sites of enzymes. Some lipid-soluble vitamins have similar functions but others, such as vitamin D and some metabolites of vitamin A, act more like hormones, binding to receptors that control gene expression or other aspects of metabolism. 

As shown in Figure 6.1, thiamin consists of pyrimidine and thiazole rings, linked by a methylene bridge the alcohol group of the side chain can be esterified with one, two, or three phosphates, yielding thiamin monophosphate, thiamin diphosphate (also known as thiamin pyrophosphate, the metabolically active coenzyme), and thiamin triphosphate. The vitamin was originally named aneurine, the antineuritic vitamin, because of its function in preventing or... 

The coenzyme thiamin diphosphate (ThDP, I in Scheme 16.1), the biologically active form of vitamin Bi, is used by different enzymes that perform a vide range of catalytic functions, such as the oxidative and nonoxidative decarboxylation of a-ketoacids, the formation of acetohydroxyacids and ketol transfer bet veen sugars. 

Why are B vitamins necessary If we consider the action of B vitamins as coenzymes, the answer is clear. There is no electrophilic functional group in the 20 amino acids of proteins. Coenzymes are therefore required for enzymes to carry out electrophilic and radical catalysis. Thiamin diphosphate is by itself a... 

Of the two heterocyclic moieties present in thiamine, the thiazole ring is responsible for the biological function of thiamine diphosphate as the coenzyme of decarboxylases. The mechanism of catalytic decarboxylation (e.g., of pyruvic acid to acetaldehyde) was interpreted by Breslow in 1958. The active species is the N-ylide 40 formed from thiamine diphosphate and basic cell components ... 

The major functioning form of thiamin is as thiamin diphosphate (formerly called thiamin pyrophosphate or cocarboxylase)—thiamin combined with two phosphate groups, in which it serves as a coenzyme in a number of enzyme systems. 

Thiamin or Bj has been recognized historically as the main cause of beriberi. Thiamin exists in free and bound forms (thiamin diphosphate and the protein-phosphate-thiamin complex). The bound forms are split in the gastrointestinal tract. The absorbed thiamin acts as a coenzyme in energy metabolism, mainly in the conversion of glncose to fats. In addition, it has high implications in the functioning of peripheral nerves (nerve impulses), brain, and muscles. Thiamin deficiency causes... 

The diphosphate ester, TPP, is the physiologically active vitamer and functions as a coenzyme (67,68). The absorption, metabolism, and physiological functions of thiamine have recently been reviewed (20,67,68). 

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