Inhibition of glycine N-methyltransferase activity by folate derivatives: implications for regulation of methyl group metabolism.
Glycine N-methyltransferase, an enzyme that uses S-adenosylmethionine to methylate glycine with the production of sarcosine, was recently shown to be identical with a major folate binding protein of rat liver (Cook, R.J. and Wagner, C. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 3631-3634). We now present evidence that 5-methyltetrahydropteroylpentaglutamate (5-CH3-H4PteGlu5) is bound with high specificity, and is a powerful inhibitor of the enzyme. It is proposed that this information may be used to modify the "methyl trap" hypothesis which describes how the availability of one-carbon units is regulated by folate, vitamin B12 and methionine.
D000818:Animals; D001667:Binding, Competitive; D005492:Folic Acid / Q000031:analogs & derivatives*; D050938:Glycine N-Methyltransferase; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011624:Pteroylpolyglutamic Acids; D051381:Rats; D011919:Rats, Inbred Strains; D013763:Tetrahydrofolates / Q000378:metabolism / Q000494:pharmacology
D011624:Pteroylpolyglutamic Acids; D013763:Tetrahydrofolates; C044774:5-methyltetrahydropteroylpentaglutamate; D005492:Folic Acid; D008780:Methyltransferases; D050938:Glycine N-Methyltransferase; C494512:Gnmt protein, rat