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Effect of Dietary Methyl Group Deficiency on Folate Metabolism in Rats¹

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

The carcinogenic effects of methyl-deficient, amino acid-defined diets have been attributed to alterations in cellular methylation reactions. These diets contain no choline, and methionine is replaced by homocysteine. Hence, all methyl groups needed for methionine biosynthesis with subsequent formation of S-adenosylmethionine and polyamines must be formed de novo utilizing folate-dependent reduction of one-carbon units. In rats fed the methyl-deficient diet, there was a marked decrease in total liver folate levels. This decrease was apparent in the levels of the individual forms of folate: 10-HCO-H₄folate, 5-HCO-H₄folate, 5-CH₃-H₄folate and H₄folate. The percent of the total folate pool made up by 5-CH₃-H₄folate did not change, however, until after the rats had been fed the methyl-deficient diet for 4 wk, and then an increase was seen. After the methyl-deficient rats were switched to a nutritionally adequate control diet containing methionine and choline, all values rapidly reversed. Increased use of folate for methyl group biosynthesis may be responsible for the loss of folates from the liver.

KEY WORDS: • folate • methyl deficiency • hepatocellular carcinoma • 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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