The effects of vitamin A deficiency on hepatic folate metabolism in rats.
The effects of severe vitamin A deficiency (liver retinol less than 2 micrograms/g) on hepatic folate metabolism in rats were studied. The oxidation of a [ring-2-14C] histidine load or a [14C]formate load to 14CO2 was significantly depressed in vitamin A-deficient rats and those given histidine also excreted more urinary formiminoglutamic acid (FiGlu) than pair-fed controls. The increase in FiGlu excretion was not due to augmented production from histidine, implicating an impairment of FiGlu catabolism. FiGlu formiminotransferase activity was unaltered in vitamin A-deficient rats, but hepatic tetrahydrofolic acid (THF) concentration was decreased by 58% in vitamin A-deficient rats given a histidine load while 5-methyl-THF concentration was increased by 39%. Formyl-THF and total folate levels were similar to controls. A redistribution of folate coenzymes was not found in vitamin A-deficient rats not force fed histidine. A 43% decrease in 10-formyl-THF dehydrogenase activity, which generates both THF and the 14CO2 from the labeled substrates, and an 81% increase in 5,10-methylene-THF reductase activity, which generates 5-methyl-THF, were found in vitamin A-deficient rats. It appears that the production of severe vitamin A deficiency results in selective changes in the activities of hepatic folate-dependent enzymes, so that when a load of a one-carbon donor is given, THF concentration decreases and metabolism of the load is impaired.
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D000818:Animals; D004224:Diterpenes; D005492:Folic Acid / Q000378:metabolism*; D005565:Formiminoglutamic Acid / Q000378:metabolism; D006639:Histidine / Q000008:administration & dosage / Q000378:metabolism; D006638:Histidine Ammonia-Lyase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D000084562:Retinyl Esters; D012435:S-Adenosylhomocysteine / Q000032:analysis; D012436:S-Adenosylmethionine / Q000032:analysis; D014559:Urocanate Hydratase / Q000378:metabolism; D014801:Vitamin A / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014802:Vitamin A Deficiency / Q000378:metabolism*
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate; D006639:Histidine; D012436:S-Adenosylmethionine; D005565:Formiminoglutamic Acid; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D014559:Urocanate Hydratase; D006638:Histidine Ammonia-Lyase