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Carbon Flow through the Hepatic Folate-Dependent One-Carbon Pool Is Not Altered in Vitamin A-Deficient Rats^1,2,

Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706

Vitamin A status can influence a number of enzymes and coenzymes involved in folate-dependent one-carbon metabolism as well as subsequent methyl group metabolism. Tracer kinetic techniques were used in the present study to assess the physiological importance of vitamin A deficiency on the de novo synthesis of methionine via the hepatic folate-dependent one-carbon pool. Vitamin A-deficient (0 retinol equivalents (RE) retinyl palmitate/g diet) rats were fed their respective diet for 11 wk, whereas control rats (1.2 RE retinyl palmitate/g diet) were food restricted to match the growth rate exhibited by the vitamin A-deficient group. After the dietary treatment period, duodenal cannulated rats were continuously infused with L-[3-¹⁴C] serine and L-[methyl-³H] methionine until a plateau specific radioactivity was exhibited with respect to the hepatic serine and methionine pools, indicating a steady state had been achieved. The hepatic concentration of both S-adenosylmethionine and S-adenosylhomocysteine were elevated in vitamin A-deficient rats. However, vitamin A-deficient rats exhibited similar kinetic values compared with control rats fed a vitamin A-sufficient diet. The irreversible loss rate of hepatic serine and methionine, the transfer quotient from serine to methionine and the folate-dependent flow of carbon to methionine from serine were unaffected by vitamin A status. These studies demonstrate that vitamin A deficiency does not affect the reductive carbon flow from serine to methionine because the ability to generate methionine via remethylation of homocysteine with the carbon group originating from serine was not altered in vitamin A-deficient rats. Furthermore, the data illustrate the importance of using tracer kinetic techniques to quantify metabolic flux under steady-state conditions in vivo, thereby evaluating the consequences of an abnormal condition on a physiological and functional basis.

KEY WORDS: • tracer kinetic techniques • folate • vitamin A deficiency • rats • one-carbon metabolism

¹ Supported in part by the University of Wisconsin College of Agricultural and Life Sciences and USPHS DK 35853.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom reprint requests should be addressed at Department of Nutritional Sciences, University of Wisconsin-Madison, 1415 Linden Drive, Madison, WI 53706.

Manuscript received 31 July 1995. Revision accepted 16 November 1995.