Metabolism of Formiminoglutamic Acid by Vitamin B12- and Folic Acid-deficient Rats Fed Excess Methionine

Abstract

The amidine carbon atom (C-Z) of L-histidine is known to be an efficient metabolic precursor of single carbon units. Following the administration of n-histidine-2-Cr4, the radioactivity has been found in CO2 and urea, in carbons 2 and 8 of purines, in the hydroxymethyl group of serine, and in choline, and creatine (l-4). The major pathway of histidine degradation which involves deamination to urocanic acid and finally, cleavage of the ring to formiminoglutamic acid (5-7) has been assumed to be the sole means of liberation of this carbon atom for “1 carbon metabolism.” The liberation of the single carbon unit can be accomplished by transfer of the formimino group to tetrahydrofolic acid. The formimino moiety is ultimately transformed into the formyl group of Nr”-formyltetrahydrofolic acid (8, 9). Folic acid or vitamin Bit-deficient rats excrete large amounts of formiminoglutamic acid in the urine (10, 11). In the more recent study (ll), the basal diet employed was limiting in the sulfur amino acids (9% casein). The addition of excess methionine to the diet, in the absence of either folic acid or vitamin Br2, significantly reduces urinary formiminoglutamic acid (11). The studies reported in this paper were prompted by this finding and were designed to clarify the nature of this effect. These studies show that radioactive COz (derived from carbon 2 of histidine) is greatly increased following the administration of excess methionine to the deficient animal. Furthermore, the evidence presented is consistent with the view that methionine does not divert histidine metabolism from the urocanic acid pathway, but exerts its influence at the level of formiminoglutamic acid.