Homocysteinemia in Mice with Genetic Betaine Homocysteine S-Methyltransferase Deficiency Is Independent of Dietary Folate Intake123

Elevated homocysteine (Hcy) concentrations are associated with increased risk of several chronic diseases. Hcy can be removed by methylating it to form methionine via either the betaine homocysteine S -methyltransferase (BHMT) or the methionine synthase (MS) pathway. BHMT uses betaine as the methyl...

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Bibliographic Details
Published in:The Journal of nutrition 2012-09, Vol.142 (11), p.1964-1967
Main Authors: Teng, Ya-Wen, Cerdena, Ignacio, Zeisel, Steven H.
Format: Article
Language:English
Subjects:
Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions
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Summary:Elevated homocysteine (Hcy) concentrations are associated with increased risk of several chronic diseases. Hcy can be removed by methylating it to form methionine via either the betaine homocysteine S -methyltransferase (BHMT) or the methionine synthase (MS) pathway. BHMT uses betaine as the methyl donor, whereas MS uses 5-methyltetrahydrofolate. We previously found that mice with the gene encoding Bhmt deleted ( Bhmt −/− ) had altered Hcy metabolites in tissues. This study aimed to determine whether folate supplementation of Bhmt −/− mice reverses, and folate deficiency exacerbates, these metabolic changes. Bhmt −/− mice and their littermates ( Bhmt +/+ mice) were fed a folate-deficient (FD; 0 mg/kg diet), a folate control (FC; 2 mg/kg diet), or a folate-supplemented (FS; 20 mg/kg diet) diet for 4 wk. Bhmt −/− mice had higher plasma Hcy and hepatic S -adenosylhomocysteine (AdoHcy) concentrations and had lower hepatic S -adenosylmethionine (AdoMet) concentrations compared with Bhmt +/+ mice for all diets. Although the FD diet increased plasma Hcy ( P < 0.05) and hepatic AdoHcy ( P < 0.001) concentrations in Bhmt +/+ mice compared with FC and FS mice, the FD diet had no effect on the metabolites measured in Bhmt −/− mice. The FS diet did not ameliorate elevated plasma Hcy and elevated hepatic AdoHcy concentrations but did increase hepatic AdoMet concentrations in Bhmt −/− mice ( P < 0.001) compared with FD and FC mice. We conclude that the BHMT pathway is a major route for the elimination of Hcy in mice and that the MS pathway has little excess capacity to methylate the Hcy that accumulates when the BHMT pathway is blocked.
ISSN:0022-3166
1541-6100
DOI:10.3945/jn.112.166835