COENZYMES DERIVED FROM B VITAMINS 159 



oxalacetic acid and oxalsuecinic acid, may be assumed to undergo decar- 

 boxylase reactions analogous to those found for pyruvic and keto- 

 glutaric acids. However, these two acids not only are cc-keto, but also 

 B-keto acids, and they normally undergo /^-decarboxylation rather than 

 cleaving at the alpha bond. 



The reactions of pyruvic acid which are catalyzed by the thiamine 

 derivative were shown in 1936 not to be limited to simple decarboxyla- 

 tions. It was found that the coenzyme for carboxylase also is an essential 

 component of the enzymatic systems by which pyruvic acid is oxidized 

 in animal tissue, and that the initial reaction is one in which a dehydro- 

 genation takes place simultaneously with the decarboxylation. 133 A num- 

 ber of different processes are now known which require the thiamine 

 coenzyme, but all can be explained on the basis of the catalysis of one 

 of these two types of reactions: (1) simple decarboxylation of either 

 pyruvic or a-ketoglutaric acid, or (2) oxidative decarboxylation of one 

 of these two metabolites. 



The experimental work which led to the identification of most of the 

 reactions in which thiamine pyrophosphate participates has been pre- 

 sented in detail in several reviews. 88 - 134, 135 



The coenzyme of thiamine has been shown to be essential for reac- 

 tions in which the following substances are produced from pyruvic acid: 

 acetaldehyde, acetic acid, molecular hydrogen, lactic acid, a reactive 

 phosphorylated derivative of acetic acid, formic acid, acetoin (acetyl- 

 methylcarbinol) , acetylethylcarbinol, dicarboxylic acids containing four 

 carbon atoms, citric acid, a-ketoglutaric acid, acetoacetic acid, and carbon 

 dioxide and water. On the basis of the diverse chemical nature of the 

 substances listed it might be inferred that a number of functions would 

 necessarily have to be ascribed to the single catalyst. However, two 

 related hypotheses, independently advanced, suggest mechanisms by 

 which it is possible to explain in terms of a general type reaction most, 

 if not all, of the reactions, both aerobic and anaerobic, catalyzed by 

 thiamine pyrophosphate. 136 ' 137 Although the hypothetical intermediates 

 postulated for these reactions have not been experimentally demonstrated 

 (and it may be impossible to do so) it is believed that the extension of 

 these hypotheses offers the most convenient method for presenting the 

 reactions catalyzed by the thiamine coenzyme and enables one to better 

 appreciate the chemical relationships between the various products of 

 these reactions. The individual reactions will therefore be discussed from 

 the standpoint of the postulated mechanisms. 



The diverse reactions of pyruvic acid catalyzed by thiamine-containing 

 enzymes can be logically explained if it is assumed that the holoenzyme 

 activates pyruvic acid in a manner such that three fragments are made 



