Thiamin diphosphate, decarboxylations structure

We see that the essence of the action of thiamin diphosphate as a coenzyme is to convert the substrate into a form in which electron flow can occur from the bond to be broken into the structure of the coenzyme. Because of this alteration in structure, a bond breaking reaction that would not otherwise have been possible occurs readily. To complete the catalytic cycle, the electron flow has to be reversed again. The thiamin-bound cleavage product (an enamine) from either of the adducts in Eq. 14-20 can be reconverted to the thiazolium dipolar ion and an aldehyde as shown in step b of Eq. 14-21 for decarboxylation of pyruvate to acetaldehyde. 

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... 

Figure 14-2 (A) Stereoscopic view of the active site of pyruvate oxidase from the bacterium Lactobacillus plantarium showing the thiamin diphosphate as well as the flavin part of the bound FAD. The planar structure of the part of the intermediate enamine that arises from pyruvate is shown by dotted lines. Only some residues that may be important for catalysis are displayed G35 , S36 , E59 , H89 , F12T, Q122 , R264, F479, and E483. Courtesy of Georg E. Schulz.119 (B) Simplified view with some atoms labeled and some side chains omitted. The atoms of the hypothetical enamine that are formed from pyruvate, by decarboxylation, are shown in green.

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-... 

Studies on thiamine (vitamin Bi) catalyzed formation of acyloins from aliphatic aldehydes and on thiamine or thiamine diphosphate catalyzed decarboxylation of pyruvate have established the mechanism for the catalytic activity of 1,3-thiazolium salts in carbonyl condensation reactions. In the presence of bases, quaternary thiazolium salts are transformed into the ylide structure (2), the ylide being able to exert a cat ytic effect resembling that of the cyanide ion in the benzoin condensation (Scheme 2). Like cyanide, the zwitterion (2), formed by the reaction of thiazolium salts with base, is nucleophilic and reacts at the carbonyl group of aldehy s. The resultant intermediate can undergo base-catalyzed proton... 

An elegant work is reported concerning the oxidation of 2-alkyl and 2-benzylthia-zolium salts, in the presence of a base, with the scope of finding a structural relationship for the thiamine-bound intermediate which intervene in the oxidative decarboxylation of a-ketoacids catalysed by thiamin diphosphate-dependent enzymes. 2-Alkyl and 2-benzylthiazolium salts, which are not electroactive, can be transformed into electroactive species by treatment with the base (trimethylsilyl)amide. Subsequent anodic oxidation affords the corresponding symmetrical dimers, by an EC mechanism (Scheme 72). As expected, the stabilizing effect of the substituents R, R at the a-carbon on the radical cation follows the order H < Me < OMe. When R is aryl, electron-donating p-substituents again enhance the enamine oxidation. 

Structures of Thiamin-Dependent Enzymes 4. The Variety of Enzymatic Reactions Involving Thiamin 5. Oxidative Decarboxylation and 2-Acetylthiamin Diphosphate. 6. Thiamin Coenzymes in Nerve Action 753. .. Table 14-4 Some Pyruvoyl Enzymes... 

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