Effect of dietary methyl group deficiency on one-carbon metabolism in rats.

Cook RJ, Horne DW, Wagner C
J Nutr. 1989 119 (4): 612-7

PMID: 2703919 · DOI:10.1093/jn/119.4.612

Amino acid-defined diets deficient in methyl groups have been shown to result in a very high incidence of hepatocellular carcinoma. It has been suggested that this is a result of decreased levels of S-adenosylmethionine and the undermethylation of DNA. Accordingly, the enzyme glycine N-methyltransferase (GNMT, EC 2.1.1.20) may play a major role in maintaining the levels of S-adenosylmethionine in liver in response to changes in dietary methionine. The effect of methyl-deficient, amino acid-defined diets on GNMT activity and S-adenosylmethionine levels in rat liver was therefore investigated. When rats were fed a defined amino acid diet containing no choline in which homocysteine was substituted for the methionine of the control diet at an equimolar level, there was a rapid and marked decrease in growth rate in spite of the fact that the rats consumed 85% of the food eaten by control rats fed a nutritionally adequate, defined amino acid diet. The GNMT activity in livers of methyl-deficient rats decreased rapidly, but there was no difference in amount of GNMT protein as measured immunologically. In methyl-deficient rats, the levels of S-adenosylmethionine were maintained but the levels of S-adenosylhomocysteine were rapidly elevated compared to control values. These changes are consistent with the postulated role of GNMT in regulating methyl group metabolism.

MeSH Terms (17)

Amino Acids Animals Carbon Choline Deficiency Diet Glycine N-Methyltransferase Liver Male Methionine Methylation Methyltransferases Organ Size Rats Rats, Inbred F344 S-Adenosylhomocysteine S-Adenosylmethionine Weight Gain

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