Thiamin diphosphate metabolism

Thiamin has a central role in energy-yielding metabo-hsm, and especially the metabohsm of carbohydrate (Figure 45-9). Thiamin diphosphate is the coenzyme for three multi-enzyme complexes that catalyze oxidative decarboxylation reactions pymvate dehydrogenase in carbohydrate metabolism a-ketoglutarate dehydro-... 

Thiamin deficiency can result in three distinct syndromes a chronic peripheral neuritis, beriberi, which may or may not be associated with heart ilure and edema acute pernicious (fulminating) beriberi (shoshin beriberi), in which heart failure and metabolic abnormalities predominate, without peripheral neuritis and Wernicke s encephalopathy with KorsakofPs psychosis, which is associated especially with alcohol and dmg abuse. The central role of thiamin diphosphate in... 

Thiamine diphosphate (TDP) is an essential coenzyme in carbohydrate metabolism. TDP-dependent enzymes catalyze carbon-carbon bond-breaking and -forming reactions such as a-keto acid decarboxylations (oxidative and non-oxidative) and condensations, as well as ketol transfers (trans- and phospho-ketolation). Some of these processes are illustrated in Fig. 12. 

Thiamine (vitamin Bi), in the form of thiamine diphosphate (TPP), is a coenzyme of some considerable importance in carbohydrate metabolism. Dietary deficiency leads to the condition beriberi, characterized by neurological disorders, loss of appetite, fatigue, and muscular weakness. We shall study a number of... 

The intermediary metabolism has multienzyme complexes which, in a complex reaction, catalyze the oxidative decarboxylation of 2-oxoacids and the transfer to coenzyme A of the acyl residue produced. NAD" acts as the electron acceptor. In addition, thiamine diphosphate, lipoamide, and FAD are also involved in the reaction. The oxoacid dehydrogenases include a) the pyruvate dehydrogenase complex (PDH, pyruvate acetyl CoA), b) the 2-oxoglutarate dehydrogenase complex of the tricarboxylic acid cycle (ODH, 2-oxoglutarate succinyl CoA), and c) the branched chain dehydrogenase complex, which is involved in the catabolism of valine, leucine, and isoleucine (see p. 414). 

In most organisms undergoing aerobic metabolism, pyruvate is oxidized to acetyl-CoA in a complex process involving its decarboxylation (Eq. 10-6). This oxidative decarboxylation, like the decarboxylation of pyruvate to acetaldehyde, requires thiamin diphosphate. In addition, an array of other catalysts participate in the process (see Fig. 15-15). Among these are the electron carrier flavin adenine diphosphate (FAD), which is derived from the vitamin riboflavin. Like NAD+, this... 

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. 

Most known thiamin diphosphate-dependent reactions (Table 14-2) can be derived from the five halfreactions, a through e, shown in Fig. 14-3. Each halfreaction is an a cleavage which leads to a thiamin- bound enamine (center, Fig. 14-3) The decarboxylation of an a-oxo acid to an aldehyde is represented by step b followed by a in reverse. The most studied enzyme catalyzing a reaction of this type is yeast pyruvate decarboxylase, an enzyme essential to alcoholic fermentation (Fig. 10-3). There are two 250-kDa isoenzyme forms, one an a4 tetramer and one with an ( P)2 quaternary structure. The isolation of ohydroxyethylthiamin diphosphate from reaction mixtures of this enzyme with pyruvate52 provided important verification of the mechanisms of Eqs. 14-14,14-15. Other decarboxylases produce aldehydes in specialized metabolic pathways indolepyruvate decarboxylase126 in the biosynthesis of the plant hormone indoIe-3-acetate and ben-zoylformate decarboxylase in the mandelate pathway of bacterial metabolism (Chapter 25).1243/127... 

The oxidative cleavage of an a-oxoacid is a major step in the metabolism of carbohydrates and of amino acids and is also a step in the citric acid cycle. In many bacteria and in eukaryotes the process depends upon both thiamin diphosphate and lipoic acid. The oxoacid anion is cleaved to form C02 and the remaining acyl group is combined with coenzyme A (Eq. 15-33). 

This vitamin acts as a coenzyme in the metabolism of carbohydrates and is present in all living tissues. It acts in the form of thiamin diphosphate in the decarboxylation of a-keto acids and is referred to as cocarboxylase. Thiamin is available in the form of its chloride or nitrate, and its structural formula is shown in Figure 9-12. The molecule contains two basic nitrogen atoms one is in the primary amino group, the other in the quater-... 

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... 

Hohmann S and Meacock PA (1998) Thiamin metabolism and thiamin diphosphate-dependent enzymes in the yeast Saccharomyces cerevisiae. genetic regulation. Bio-chimica et Biophysica Acta 1385, 201-19. 

Gotz, F., Sedewitz, B. (1990), Physiological role of pymvate oxidase in the aerobic metabolism of Lactobacillus plantarum, in Biochemistry and Physiology of Thiamin Diphosphate Enzymes (Bisswanger, H., Ullrich, J., eds.), pp. 286-293. VCH, Weinheim. 

Thiamin (Vitamin Bl), biosynthesized by most prokaryotes and eukaryotes in its active form thiamin diphosphate (ThDP), is an essential cofactor for several enzymes involved in carbohydrate and amino acid metabolism. Most bacteria, as well as fungi and plants, are able to produce thiamin de novo, while mammals depend solely on the dietary uptake [335-337],... 

TMP), thiamine diphosphate (TDP also known as thiamine pyrophosphate, TPP), and thiamine triphosphate (TTP). TDP, the best characterized form, in its role as a eoenzyme for molecules involved in carbohydrate metabolism e.g. transketolase and pyruvate dehydrogenase) is important for energy production and numerous metabolic functions (Lonsdale 2006). 

The decarboxylation and oxidation of pyruvate to form acetyl CoA requires the coenzyme thiamin diphosphate, which is formed from vitamin (section 11.6.2). In thiamin deficiency, this reaction is impaired, and deficient subjects are unable to metabolize glucose normally. Especially after a test dose of glucose or moderate exercise they develop high blood concentrations of pyruvate and lactate. In some cases this may be severe enough to result in life-threatening acidosis. 

Thiamin has a central role in energy-yielding metabolism, and especially the metabolism of carbohydrates. Thiamin diphosphate (also known as thiamin pyrophosphate see Figure 11.12) is the coenzyme for three multienzyme complexes that catalyse oxidative decarboxylation of the substrate linked to reduction of enzyme-bound lipoamide, and eventually reduction of NADto NADH ... 

Thiamin diphosphate is also the coenzyme for transketolase, in the pentose phosphate pathway of carbohydrate metabolism (section 5.4.2). 

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