Thiamin has a central role in energy-yielding metabolism, and especially the metabolism of carbohydrates. Thiamin diphosphate is the coenzyme for three multi-enzyme complexes that catalyze oxidative decarboxylation reactions: pyruvate dehydrogenase in carbohydrate metabolism; α-ketoglutarate dehydrogenase in the citric acid cycle; and the branched-chain keto-acid dehydrogenase involved in the metabolism of leucine, isoleucine, and valine. In each case, the thiamin diphosphate provides a reactive carbon on the thiazole moiety that forms a carbanion, which then adds to the carbonyl group. The addition compound is then decarboxylated, eliminating CO2. Thiamin diphosphate is also the coenzyme for transketolase, in the pentose phosphate pathway (Murray et. al. 2009).
Thiamine pyrophosphate is the biologically active form of the vitamin, formed by the transfer of a pyrophosphate group from adenosine triphosphate (ATP) to thiamine (Figure 7). It as a coenzyme in the formation or degradation of α-ketols by transketolase and in the oxidative decarboxylation of α-keto acids (Harvey & Ferrier, 2011).
Thiamine pyrophosphate is the biologically active form of the vitamin, formed by the transfer of a pyrophosphate group from adenosine triphosphate (ATP) to thiamine (Figure 7). It as a coenzyme in the formation or degradation of α-ketols by transketolase and in the oxidative decarboxylation of α-keto acids (Harvey & Ferrier, 2011).
Thiamin deficiency can result in three distinct syndromes: a chronic peripheral neuritis, beriberi, which may or may not be associated with heart failure and edema; acute pernicious (fulminating) beriberi (shoshin beriberi), in which heart failure and metabolic abnormalities predominate, without peripheral neuritis; and Wernicke encephalopathy with Korsakoff psychosis, which is associated especially with alcohol and narcotic abuse. The role of thiamin diphosphate in pyruvate dehydrogenase means that in deficiency there is impaired conversion of pyruvate to acetyl CoA. In subjects on a relatively high carbohydrate diet, this results in increased plasma concentrations of lactate and pyruvate, which may cause life-threatening lactic acidosis (Harvey & Ferrier, 2011).
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