CARBON FLOW-THROUGH THE HEPATIC FOLATE-DEPENDENT ONE-CARBON POOL IS NOT ALTERED IN VITAMIN-A-DEFICIENT RATS

Vitamin A status can influence a number of enzymes and coenzymes invol ved in folate-dependent one-carbon metabolism as well as subsequent me thyl group metabolism. Tracer kinetic techniques were used in the pres ent study to assess the physiological importance of vitamin A deficien cy on the de novo synthesis of methionine via the hepatic folate-depen dent one-carbon pool. Vitamin A-deficient (0 retinol equivalents (RE) retinyl palmitate/g diet) rats were fed their respective diet for 11 w k, whereas control rats (1.2 RE retinyl palmitate/g diet) were food re stricted to match the growth rate exhibited by the vitamin A-deficient group. After the dietary treatment period, duodenal cannulated rats w ere continuously infused with L-[3-C-14] serine and L-[methyl-H-3] met hionine until a plateau specific radioactivity was exhibited with resp ect to the hepatic serine and methionine pools, indicating a steady st ate had been achieved. The hepatic concentration of both S-adenosylmet hionine and S-adenosylhomocysteine were elevated in vitamin A-deficien t rats. However, vitamin A-deficient rats exhibited similar kinetic va lues compared with control rats fed a vitamin A-sufficient diet. The i rreversible loss rate of hepatic serine and methionine, the transfer q uotient from serine to methionine and the folate-dependent flow of car bon to methionine from serine were unaffected by vitamin A status. The se studies demonstrate that vitamin A deficiency does not affect the r eductive 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 r ats. Furthermore, the data illustrate the importance of using tracer k inetic techniques to quantify metabolic flux under steady-state condit ions in vivo, thereby evaluating the consequences of an abnormal condi tion on a physiological and functional basis.