Methylmalonate, Formiminoglutamate and Aminoimidazolecarboxamide Excretion of Vitamin B12-deficient Germfree and Conventional Rats

Abstract

In order to evaluate the net influence of microbial metabolism on vitamin B12 nutriture, growth and urinary methylmalonic acid (MMA), aminoimidazolecarboxamide (AIC) and formiminoglutamic acid (FIGLU) were measured in male germfree and conventional rats fed a low methionine diet with or without vitamin B12 and during dietary supplementation with 1% of DL-methionine. Growth was retarded significantly among vitamin B12-deficient rats of both environments in comparison with their respective vitamin B12-supplemented controls. MMA excretion rose to 20 times the control level in conventional deficient rats but was only slightly elevated among germfree deficient animals. Though less dramatic, the same trend was true of AIC excretion. FIGLU excretion was elevated significantly in deficient animals of both environments. Methionine ingestion further enhanced MMA excretion of conventional deficient rats, suggesting that it served as a metabolic precursor. AIC excretion was unaffected by methionine feeding in contradiction to an earlier report. FIGLU excretion was depressed by DL-methionine supplementation to a greater extent among conventional than among germfree rats, perhaps indicating poor utilization of the D-isomer by germfree animals. These results show that MMA excretion is an unreliable index of vitamin B12 deficiency in the absence of conventional microbial metabolism and that the vitamin B12 requirement may be reduced in the germfree state.