Methionine recycling in brain: a role for folates and vitamin B-12

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 [35S]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.