Effects of Vitamin B12 Analogues with Alternations in the Side Chains of the Corrin Ring on Urinary Methylmalonate Excretion in Vitamin B12-Deficient Rats

To study how much the side chains of the corrin ring of vitamin B₁₂ are involved in the physiological roles of the vitamin, five vitamin B₁₂ analogues (cyanocobalamin-b-monocarboxylate, cyanocobalamin-d-monocarboxylate, cyanocobalamin-e-monocarboxylate, cyano-13-epicobalamin, and cyanocobalamin(c-lactam)) with alternations in the side chains were synthesized chemically and then administered orally and intravenously to vitamin B₁₂-deficient rats. Male rats fed a vitamin B₁₂-deficient diet for 11 wk developed a severe vitamin B₁₂ deficiency with a high urinary methylmalonate excretion (223.8 ± 136.2 μmol/d) and ~97% (1.2±0.7ng/g tissue) lower hepatic vitamin B₁₂ content. Oral and intravenous administration of cyanocobalamin-b-,-d-, and -e-monocarboxylates and cyano-13-epicobalamin could not improve the severe vitamin B₁₂-deficient status of the rats, indicating that the b-, d-, and e-propionamide side chains of the corrin ring of vitamin B₁₂ are important in the absorption, transport, and function of the vitamin in rats. Urinary methylmalonate excretion of the rats that were intravenously administered cyanocobalamin(c-lactam) increased twice as much as those of the other analogue-supplemented rats, suggesting that cyanocobalamin(c-lactam) act as a powerful Cbl-antagonist. The results also indicate that mammalian cells do not contain a system for synthesizing complete vitamin B₁₂ from these analogues.