Uptake and metabolism of [3H]folate by normal and by vitamin B-12- and methionine-deficient rats.
The uptake of an injected dose of [3H]folic acid and its metabolism to pteroylpoly-gamma-glutamate forms by the livers and kidneys of vitamin B-12- and methionine-deficient and -supplemented rats were investigated. The initial hepatic uptake of the labeled folate dose was the same in deficient and supplemented animals, demonstrating no involvement of vitamin B-12 or methionine in folate transport. At longer time periods, a decreased hepatic net uptake of labeled folate was observed in the deficient animals compared to supplemented animals, and this was directly correlated with the decreased ability of the deficient animals to synthesize pteroylpolyglutamates. The absolute rate of loss of labeled pteroylmonoglutamate from liver was the same in deficient and supplemented animals. These data are best explained by a modification of the 'methyl trap' hypothesis for the interrelationship of vitamin B-12 and folate metabolism. Vitamin B-12 deficiency can lead to lowered levels of 5-methyltetrahydrofolate:homocysteine methyltransferase, creating a functional folate deficiency by 'trapping' an increased proportion of folate as the methyl derivative. In addition, as methyltetrahydrofolate is a poor substrate for folylpoly-gamma-glutamate synthetase, there is a decreased synthesis of pteroylpolyglutamates, the forms of the vitamin that are preferentially retained by tissues. This results in decreased tissue folate levels under conditions of vitamin B-12 deficiency. Vitamin B-12 and methionine deficiency had no significant effect on the distribution of endogenous pteroylpolyglutamates in rat liver and kidney, although total endogenous folate in rat liver was reduced by about 60%. The distribution of labeled pteroylpolyglutamates in rat liver and kidney 48 h after the tracer dose of [3H]folate closely resembled the endogenous distribution in these tissues.
D000818:Animals; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000172:deficiency* / Q000627:therapeutic use; D051381:Rats; D014805:Vitamin B 12 / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000188:drug therapy / Q000378:metabolism*
D005492:Folic Acid; D008715:Methionine; D014805:Vitamin B 12