Effect of dietary methyl group deficiency on one-carbon metabolism in rats.
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.
Cook
R J
RJ
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37212.
Horne
D W
DW
Wagner
C
C
D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D002244:Carbon / Q000378:metabolism*; D002796:Choline Deficiency / Q000378:metabolism*; D004032:Diet; D050938:Glycine N-Methyltransferase; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008715:Methionine / Q000172:deficiency*; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D011916:Rats, Inbred F344; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism*; D015430:Weight Gain
D000596:Amino Acids; D002244:Carbon; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D008780:Methyltransferases; D050938:Glycine N-Methyltransferase; C494512:Gnmt protein, rat