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Methylmalonic Acid Metabolism of Germfree and Conventional Vitamin B-12 Deprived Rats Fed Precursors of Methylmalonate¹

Department of Nutrition, University of California, Davis, California 95616, and Department of Nutritional Sciences, University of California, Berkeley, California 94720

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 CONV 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.

KEY WORDS: • germfree rats • methylmalonic acid • vitamin B-12 • formiminoglutamic acid • intestinal flora

¹ Data are from a thesis submitted by S. C.-H. Chen to the Graduate School, University of California, Davis, in partial fulfillment of the requirement for the Ph.D. degree. Portions of this study were supported by NIH grant AM 19970.

² Present address: Department of Food and Nutrition, Iowa State University, Ames, Iowa 50011.

Manuscript received 2 May 1978.