Metabolic demands for coenzyme B₁₂-dependent mutase increased by thiamin deficiency

Abstract

Investigated was the possibility that a thiamin deficiency may increase catabolism of metabolites by the coenzyme B₁₂-dependent methylmalonyl CoA (MM-CoA) mutase pathway leading to succinyl-CoA. Nine-month-old rats, those mildly depleted of vitamin B₁₂ and their controls, were subjected to 26 days of thiamin deficiency. Sub-groups included: controls (CC), thiamin-deficient (TD), vitamin B₁₂-depleted (BD) and a thiamin-deficient subgroup that was also mildly depleted of vitamin B₁₂ (TD+BD). Dietary valine (1%) was used to increase metabolic demands for coenzyme B₁₂-dependent MM-CoA of all 4 subgroups. Thiamin deficiency (TD) promoted a 133% increase in urinary excretion of methylmalonic acid (MMA). Thiamin deficiency (TD) and the mild depletion of vitamin B₁₂ (BD) led to equivalent suppression of food-appetite in the rats. Rats mildly depleted of vitamin B₁₂ had liver-B₁₂ levels that were 78% of that of the controls, but thiamin deficiency did not affect retention of this vitamin in liver. Related studies revealed that dietary pyruvate increased excretion of MMA of younger rats that were mildly depleted of vitamin B₁₂. A possible link between increased pyruvate levels of a thiamin deficiency and an increased catabolism of branched-chain amino acids by coenzyme B₁₂-dependent mutase is proposed.