The interaction of methionine (Met) deficiency and dietary methyl donors on hepatic betaine-homocysteine methyltransferase (BHMT) gene expression

Eric I. Park, Linda S. Garrow, Jacob D. Mulligan, Norman S. Millan, Murty S. Renduchintala, Margaret A. Griffiths, Timothy A. Garrow

Research output: Contribution to journalArticlepeer-review

Abstract

High plasma homocysteine (Hcy) is a risk factor for the development of vascular disease and BHMT (EC 2.1.1.5) may have an important role in the modulation of blood Hcy. We have shown that liver BHMT gene expression is increased up to 9-fold when rats were fed a diet deficient in Met (0.1%) concomitant with excess (25 mmol/kg diet) dietary betaine (J. Nutr. Biochem. 8:541-545 1997). Using rats, we did a series of nutrition studies to evaluate the induction of hepatic BHMT gene expression by other methyl donor substrates, and to define the relationship between Met deficiency and methyl donor intake on BHMT gene expression. Met deficient (0.1%) diets with high levels of dietary choline (20 mmol/kg diet), or sulfonium analogs of betaine (37.5 mmol/kg diet), induced hepatic BHMT. Consistent with our previous report dietary-induced changes in hepatic BHMT activity are mediated by changes in steady-state mRNA level. Immunodetection also showed corresponding changes in BHMT protein. Met deficient (0.1%) diets devoid of choline or other methyl donor did not induce BHMT gene expression. Rats fed diets marginally deficient in Met (0.15%) and high levels of choline (20 mmol/kg diet) showed intermediate induction of BHMT. Our data indicate that there is a dose-dependent relationship between methyl donor intake and BHMT induction when dietary Met is limiting, and that the severity of Met deficiency may also influence the magnitude of the induction.

Original languageEnglish (US)
Pages (from-to)A814
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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