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Journal of Nutrition Vol. 119 No. 4 April 1989, pp. 612-617
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Effect of Dietary Methyl Group Deficiency on One-Carbon Metabolism in Rats1

Robert J. Cook, Donald W. Horne and Conrad Wagner*

Department of Biochemistry, Vanderbilt University School of Medicine * Veterans Administration Medical Center, Nashville, TN 37212

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.


KEY WORDS: • methyl deficiency • S-adenosylmethionine • hepatocellular carcinoma • glycine N-methyltransferase • methionine • choline

1 This work was supported by the Veterans Administration, by a grant from the American Institute for Cancer Research and by grants #DK15289 and #DK32189 from the U.S. Public Health Service.

Manuscript received 16 June 1988. Revision accepted 16 December 1988.




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