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Sub cellular localization of folate turnover and folate dependent enzyme activity in mouse brain



Sub cellular localization of folate turnover and folate dependent enzyme activity in mouse brain



Journal of Neurochemistry 34(6): 1442-1452



Using 5-[methyl-14C]methyltetrahydrofolate and 5-[2-14C]methyltetrahydrofolate, 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 mitochondrial and synaptosomal soluble fractions exhibited a comparatively high content of labeled folate. The folate turnover rate was extremely slow. Subcellular localization of 2 folate-dependent enzymes showed that N5, N10-methylenetetrahydrofolate reductase and N5-methyltetrahydrofolate homocysteine methyltransferase activities were largely soluble, the latter exhibiting a very high specific activity in the synaptosomal lysate. One-carbon metabolism and the compartmentalization of folate function in mouse brain are discussed.

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Accession: 006532461

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PMID: 6247446


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