IV VITAMINBIOSYN THESIS II3 



Interestingly enough, strains 9185 and 56501 can grow on P and large amounts of exogenous 

 T even though T is normally excreted into the medium. This is best explained as due to a 

 competition of T with its precursor, t, for the pyrimidine compound P. It is believed that 

 the P-t pathway of thiamine synthesis is the major one in Neurospora. 



Although animal tissues are incapable of synthesizing thiamine, enzymes occur 

 in liver which catalyze the phosphorylation of the vitamin to its pyrophosphate 

 (Bessey et al., 1953) : 



Mg"" 



Thiamine -r ATP > thiamine pyrophosphate + AMP 



liver, yeast 



Thiamine pyrophosphate, is active as a coenzyme in the decarboxylation of 

 pyruvate and a-ketoglutarate (Reed, 1953) and in the transketolase reaction. 

 Lipothiamide pyrophosphate, a conjugate of thiamine with lipoic acid, functions 

 as the active coenzyme for the decarboxylation of a-keto acids in certain micro- 

 organisms. 



4. Riboflavin 



Isotope experiments with yeast have established that the a and carboxyl carbons 



of glycine are precursors of carbons 4a and 9a, respectively, of the riboflavin 



molecule (Plant, 1954a; Fig. 52). The nitrogen of glycine is also incorporated into 



riboflavin. Moreover, formate is a precursor of 



carbon 2 while COj gives rise to carbon 4 of 



-C=0 riboflavin. This pattern of labelling is reminiscent 



of that observed in the biosynthesis of purines. 



Moreover, it is to be noted that the ribityl group 



of riboflavin is in the same position as that of the 



r ■, n ■ ribose of adenosine. This suggests that purines are 

 Fig. 52. Structure of riboflavin. ., „ . . ^ ■ . , , . 



riboflavin precursors in yeast. Consistent with this 



concept is the fact that purines or their ribosides or ribotides enhance riboflavin 

 synthesis by yeast under conditions where growth is unaflfected (Brown et al., 1 955) . 

 The amino acids, L-threonine, L-serine and L-tyrosine are also stimulatory, the 

 stimulatory effects of the amino acids and purine compounds being cumulative 

 (Goodwin and Pendlington, 1954). 



Uniformly labelled adenine-''*C is efficiently incorporated into the pyrimidine 

 portion of riboflavin but adenine-8-^'*C is not a precursor (McNutt, 1954, 1956). 

 Thus, carbon 8 of the adenine is lost during the condensation of the pyrimidine 

 portion of the riboflavin molecule with the dimethyl benzene precursor. The 

 origin of the dimethyl benzene end of the molecule has not as yet been fully clari- 

 fied. Acetic- 1 -^'*C is a precursor of carbons 6 and 7 and 8a and loa. A more 

 random pattern of labelling is observed, however, with acetic-2-^'*C as substrate. 

 Most of the label is found in the methyl groups and in carbons 5 and 8 

 but there is also significant radioactivity in carbons 6 and 7, and 8a and loa, 

 the carbon atoms derived from acetate- i-^'^C. This suggests that a tricarboxylic 

 acid cycle metabolite is an intermediate in the incorporation of acetate into the 

 aromatic ring of riboflavin (Plaut, 1954a; Klungsoyr, 1954). The labelling of the 

 aromatic ring with glucose- i-'^'C or glucose-6-^''C as substrate is similar to that 



Literature p. 124 



