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Effect of Methionine on Specific Folate Coenzyme Pools in Vitamin B₁₂ Deficient and Supplemented Rats^{1, 2,}

Department of Nutritional Sciences, University of California, Berkeley, California 94720

Folic acid coenzyme patterns were studied in the liver of rats fed 20% soy protein diets either deficient or supplemented with vitamin B₁₂ and with or without added DL-methionine. Vitamin B₁₂ deficiency was confirmed by a 10-fold elevation of urinary methylmalonic acid, and secondary folate deficiency was indicated by elevated urinary formiminoglutamic acid in vitamin B₁₂- and methionine-deficient groups. A radioisotopic labeling method was developed for assay of liver folates with subsequent separation of folate compounds by improved DEAE-cellulose chromatography. Results showed that the secondary folate deficiency in rats fed the doubly deficient diet occurred in the folate di-, tri- and pentaglutamates, composing 90 to 95% of the total liver folates. The pool sizes of the folate monoglutamates remained relatively unchanged. Added dietary methionine produced rapid restoration of the higher folate polyglutamates. The amount of 5-methyltetrahydrofolic acid did not increase in the vitamin B₁₂-deficient state, supporting the view that constant levels of this monoglutamate as well as others are maintained by intracellular conditions. The amounts of the polyglutamates, on the other hand, are controlled by dietary availability of vitamin B₁₂ or methionine.

KEY WORDS: • folic acid • vitamin B₁₂ • methionine

¹ A portion of this work was presented at the VIIIth International Congress of Nutrition in Prague, Czechoslovakia, September 4, 1969.

² This study was supported in part by NIH Grant no. AM 08171.

³ Present address: Department of Nutrition, Harvard School of Public Health, Boston, Mass. 02115.

Manuscript received 5 July 1972.