Biosynthesis of histidine from radioactive acetate and glucose.

Evidence has been presented in a previous paper (2) that formate is the precursor of carbon atom 2 of histidine in yeast and that the imidazole ring of the amino acid is not derived from the corresponding ring of the purine bases. The present paper is concerned with the origin of the 5 carbon chain of histidine. The studies of Edlbacher (3) indicated that histidine catabolism in liver preparations leads to chemical intermediates which yield both formate and glutamate upon acid hydrolysis. Although earlier studies on the biological formation of free glutamate from histidine were not conclusive (49), more recent investigations (10-13) have demonstrated this conversion and have established that “formate” is formed from carbon 2 of the ring (14-17). The fact that formate is both converted to histidine and formed from it suggests the possibility that the synthesis might occur by reversal of these degradative reactions. The present studies with acetate-2-Cl4 and CIJ-labeled glucose indicate that histidine synthesis in yeast does not occur by reversal of this degradative pathway.