Extremely low activity of methionine synthase in vitamin B-12-deficient rats may be related to effects on coenzyme stabilization rather than to changes in coenzyme induction

Severely vitamin B-12 (B-12)-deficient rats were produced by feeding a B-12 -deficient diet. The status of B-12 deficiency was confirmed by an increase in urinary methylmalonate excretion and decreases in liver B-12 concentrat ions and cobalamin-dependent methionine synthase activity. Rat liver methio nine synthase existed almost exclusively as the holoenzyme. In B-12-deficie nt rats, the level of methionine synthase protein was lower, although the m RNA level was not significantly different from that of control rats. When m ethylcobalamin, the coenzyme for methionine synthase, was administered to t he B-12-deficient rats, growth, liver B-12 concentrations and urinary excre tion of methylmalonate were reversed although not always to control (B-12-s ufficient) levels in a short period. During this recovery process, methioni ne synthase activity and its protein level increased, whereas the mRNA leve l was unaffected. We reported previously that rat apomethionine synthase is very unstable and is stabilized by forming a complex with methylcobalamin. Thus, the extremely low activity of methionine synthase in B-12-deficient rats may be related to effects on "coenzyme stabilization" (stabilization o f the enzyme by cobalamin binding) rather than to changes in "coenzyme indu ction".