170 THE BIOCHEMISTRY OF B VITAMINS 



(1) Are there other cof actors which can catalyze the decarboxylation 

 reactions of pyruvic and ketoglutaric acids? A cof actor which is essential 

 for the oxidative decarboxylation of pyruvic acid by certain bacteria has 

 been demonstrated recently. 100 Its structure is not yet known, but on the 

 basis of stability studies it cannot be related chemically to the usual 

 coenzyme. However, no report has been made which would justify the 

 conclusion that the system does not also contain thiamine pyrophosphate. 



(2) Is thiamine pyrophosphate necessary for the biological decar- 

 boxylation of other a-keto acids? One enzyme system in which oxalacetate 

 is cleaved by an a-decarboxylation (oxidative) rather than a /3-cleavage 

 has been reported. 157 This is an oxidative decarboxylation and produces 

 malonic acid. The reaction is analogous to the oxidative decarboxylation 

 of a-ketoglutaric acid in which succinic acid is produced. However, in 

 this instance, the enzyme has been shown to be a porphyrin-containing 

 protein and contains no thiamine. 158 



a-Keto acids are produced by the oxidative deamination of amino 

 acids. Some of these at least are known to be metabolized by oxidative 

 decarboxylations (phenylpyruvic acid, for example, is converted to 

 phenylacetic acid). Thiamine has never been shown to be necessary for 

 these reactions; but since they have not been studied in well resolved 

 systems, one cannot make any statement concerning its function in these 

 reactions. 



(3) Is thiamine pyrophosphate a coenzyme for any type of reaction 

 other than the decarboxylation of a-keto acids? There is no apparent 

 necessity for postulating any additional type of function for the thiamine 

 coenzyme, if the reactions of the diacetyl mutase type are regarded as 

 special cases involving intermediates of a-decarboxylations. 



The Coenzymatic Functions of Biotin 



The search for the specific enzymatic reactions mediated by biotin has, 

 at the time of this writing, not been wholly successful. Although consider- 

 able information is now available concerning metabolic products whose 

 syntheses depend upon the presence of biotin, the exact reactions in which 

 the biotin coenzyme participates still cannot be stated with certainty. 

 The evidence based on all the information reported to date necessitates 

 the assumption that biotin functions in several processes which seem to 

 have nothing in common — a situation which, if unexplained, leaves this 

 one member of the typical B group in a unique category. 



Four metabolic processes have been shown to be influenced by the 

 biotin available to cells or tissues: (1) the ^-decarboxylation of poly- 

 basic keto acids and the reverse carboxylation ; (2) the biosynthesis of 



