Methylmalonic Acid Metabolism of Germfree and Conventional Vitamin B-12 Deprived Rats Fed Precursors of Methylmalonate

Abstract

Experiments using germfree (GF), ex-germfree (XGF) and conventional (CONV) rats were conducted to study the relationship of intestinal microorganisms to vitamin B-12 (B-12) status and to methylmalonic acid (MMA) excretion of the host animal, since B-12 depleted GF rats have been found to excrete less than expected level of urinary MMA. The possibility that the GF rat lacks sufficient precursor of MMA was tested by feeding GF, XGF and CONY rats diets low or high in MMA precursors and examining urinary excretion of MMA and formiminoglutamic acid at intervals. The possibility that the GF rat may metabolize propionate and MMA differently from the CONV rat was examined by a MMA loading-recovery study and a CO2 collection study after [14C]propionate injection. Plasma and tissue B-12 levels were determined at the beginning and the end of the study. Results indicate that 1) lack of sufficient precursor of MMA is partly responsible for the failure of GF, B-12 deficient rat to excrete MMA, 2) GF and CONV rats metabolize propionate and MMA by the same pathways and 3) the presence of intestinal microorganism depletes the body B-12 store of the rat.