Abstract
Abstract: Using 5‐[methyl‐14C]methyltetrahydrofolate and 5‐[2‐14C]methyl‐tetrahydrofolate, the rates of uptake and turnover of the methyl and folate moieties in mouse brain were compared. The methyl moiety was taken up and retained more readily than the folate moiety. Intracerebral injections of labeled folate were used to study the retention and subcellular turnover of folate. The injected folate exchanged slowly with the endogenous pool, stabilizing after 2 days. Analyses of the subcellular distribution of label with time showed that folate underwent intercompartmental exchange in all fractions except the synaptosomal particulate fractions, which appeared to contain a folate pool inert to exchange. The mitochondria] and synaptosomal soluble fractions exhibited a comparatively high content of labeled folate. The folate turnover rate was extremely slow. Subcellular localization of two folate‐dependent enzymes showed that /V5, Arlo‐methylenetetrahydrofolate reductase and N5‐methyltetrahydrofolate homocysteine methyltransferase activities were largely soluble, the latter exhibiting a very high specific activity in the synaptosomal lysate. The implications of these findings with respect to one‐carbon metabolism and the compartmentalization of folate function in mouse brain are discussed.
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