COENZYMES DERIVED FROM B VITAMINS 197 



biological systems. It may simply be formic acid; it may be a reactive 

 derivative similar to the phosphorylated derivatives of acetic acid. An- 

 other possibility is that the "formyl group" is chemically combined with 

 a "formate-carrying" coenzyme from the time of its formation until it is 

 utilized, so that the formic acid or the formate ion would not necessarily 

 be present as such. Until this question has been settled, it seems unwise 

 to designate the reactive intermediate as formic acid or formate; hence, 

 the expression "single carbon unit" has been used. 



Origin of the Single Carbon Unit. Exogenous sources of formic acid 

 itself can be utilized for syntheses requiring the single carbon units (at 

 least, by bacteria, fowl, and mammals) . 277, 273, 278 Consequently, biologi- 

 cal reactions producing formic acid may serve as sources of the single 

 carbon unit. Before isotopically labelled compounds were available, free 

 formic acid had been shown to be formed by: 



(1) many species of bacteria, in most cases by a phosphoroclastic 

 cleavage of pyruvic acid (p. 162) ; 



(2) muscle perfused with pyruvic acid (perhaps by a phosphoroclastic 

 cleavage of oc-ketoglutaric acid) (p. 167) ; 



(3) the enzymatic degradation of the imidazole nucleus of histidine 

 (by histidinase). 279 



(4) insects (mechanism unexplored). 



Other potential sources of the single carbon unit recently disclosed by 

 the use of tracers are: either carbon atom of glycine, 280,281 the /?-carbon 

 atom of serine, 282 the carboxyl carbon atom of acetic acid, 276 and the 

 carbon atoms of the N- and S-methyl groups of choline and methionine. 282 



Although the carboxyl group of pyruvic acid is the precursor of the 

 formic acid produced by bacterial fermentation, it has been shown that 

 this group can not be the primary source of the single carbon unit in the 

 metabolism of animals. 276 The simultaneous accumulation of succinic acid 

 and formic acid when muscles are perfused with pyruvic acid indicates 

 that a phosphoroclastic splitting of a-ketoglutaric acid may be an im- 

 portant source of the single carbon unit in organisms in which pyruvic 

 acid is metabolized via the tricarboxylic acid cycle (p. 223). Such a reac- 

 tion could account for the ultimate incorporation of the carboxyl carbon 

 atom of acetic acid and the carbonyl carbon atom of pyruvic acid into 

 compounds in the same positions where labelled carbon atoms of formic 

 acid have been shown to appear. (In aerobic metabolism, these particular 

 carbon atoms in the acetic and pyruvic acid molecules eventually form 

 the cc-carboxyl group of a-ketoglutaric acid). Histidine was for a long 

 time believed to be the precursor of purines in animals since ingestion 

 of histidine increased the excretion of purines. 283 It was naturally assumed 

 that the histidine was the precursor of the purine's imidazole nucleus. 



