Distinct effects of folate and choline deficiency on plasma kinetics of methionine and homocysteine in rats

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Both folate and betaine, a choline metabolite, play essential roles in the remethylation of homocysteine to methionine. We have studied the effects of folate and choline deficiency on the plasma kinetics of methionine, especially remethylation of homocysteine to methionine, by means of stable isotope methodology. After a bolus intravenous administration of [ 2H 7]methionine (5 mg/kg body weight) into the rats fed with folate-, choline-, folate + choline–deficient or control diets, the plasma concentrations of [ 2H 7]methionine, demethylated [ 2H 4]homocysteine, and remethylated [ 2H 4]methionine were determined simultaneously with endogenous methionine and homocysteine by gas chromatography-mass spectrometry–selected ion monitoring. The total plasma clearance of [ 2H 7]methionine was not significantly different among groups, suggesting that the formation of [ 2H 4]homocysteine from [ 2H 7]methionine was not influenced by deficiencies of folate and choline. The area under concentration-time curve of [ 2H 4]homocysteine significantly increased in the folate- and folate + choline–deficient group as compared with the control, but not in the choline-deficient group. The time profile of plasma concentrations of [ 2H 4]methionine in the folate-deficient group was the same as the control group, whereas the appearance of [ 2H 4]methionine in plasma was delayed in the choline- and folate + choline–deficient group. These results suggested plasma levels of remethylated methionine were influenced by choline deficiency rather than folate deficiency.