Methionine Recycling in Brain: A Role for Folates and Vitamin B-12

Abstract: The recycling of methionine via homocysteine was measured in vivo in brain. After constant intravenous infusions (5 h) of both ³H-methyl] methionine and ³⁵S]methionine into rats, the ratios of ³H-methyl]methionine to ³⁵S]methionine in liver, brain and plasma were determined, Similar experiments were performed in rabbits, except that the ³H-methyl]- and ³S]methionine were injected intraventricularly. If the methyl group of methionine was removed with the formation of homocysteine and then replaced by another (unlabeled) methyl group, the specific activity of the ³H-methyl]methionine would decrease more than that of ³⁵S]methionine; i.e., the ratio of ³H-methyl]- to ³⁵S]methionine in the tissue would decline. The results showed that the ratios of ³H-methyl]- to ³⁵S]methionine in liver and brain were less than the same ratio in plasma in the rats. The comparable ratios in the brain and CSF of rabbits were less than the ratio in the injectate. Since brain contains only one enzyme capable of remethylating homocysteine to methionine, the vitamin B-12–dependent methyltetrahydrofolate-homocysteine methyltransferase (EC 2.1.1.13), our results for methionine recycling via homocysteine in brain strongly support the activity of this enzyme in brain in vivo.