Rates of oxidation of the methionine and S-adenosylmethionine methyl carbons in isolated rat hepatocytes.

The methyl group of methionine (Met) is metabolized via activation to S-adenosylmethionine (AdoMet) and subsequent transmethylation and also by a transamination-decarboxylation route. To estimate the contribution of pathways independent of AdoMet formation in the oxidation of physiological levels of Met to CO2, the oxidation rates of L-[methyl-14C]Met and L-[methyl-14C] AdoMet were compared in hepatocyte suspensions. Hepatocytes took up AdoMet from the medium and oxidized its methyl group to CO2 at a rate of 280 +/- 22 nmol/g wet cells per hour, which was constant at extracellular concentrations between 0.1 and 1.0 mM AdoMet and Met. Hepatocytes took up L-[methyl-14C]Met and reached an intracellular specific activity within 10 min that was less than 10% of the specific activity in the medium at 0.1 mM Met and 20-30% at 1.0 mM Met. In contrast, L-[methyl-14C]AdoMet formed from L-[methyl-14C]Met reached a specific activity that was 40-50% (0.1 mM Met) and 50-60% (1.0 mM Met) of the specific activity of Met in the medium. These results suggest that AdoMet is formed from a mixture of extracellular and intracellular Met. If the specific activity of AdoMet represents the pool from which Met is oxidized, then the oxidation rates of Met methyl were 1200 and 1859 nmol/(g.h) at 0.1 and 1.0 mM Met, respectively. Thus, oxidation of Met via AdoMet formation accounts for only 12% (at 1 mM Met) to 21% (at 0.1 mM Met) of the total in rat hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)