Activities of tryptophan-metabolizing enzymes in liver and brain of rats treated with aflatoxins.
Male Sprague-Dawley rats were treated ip twice daily for 10 days with mixed aflatoxins (10 micrograms/kg body weight) and then the activities of liver tryptophan 2,3-dioxygenase and brainstem tryptophan 5-hydroxylase were determined in vitro. Total tryptophan 2,3-dioxygenase activity was reduced by aflatoxin treatment while holoenzyme activity was not. Induction of tryptophan 2,3-dioxygenase activity by L-tryptophan was not altered by the treatment though induction by hydrocortisone was blocked. It is suggested that aflatoxin may alter the tryptophan 2,3-dioxygenase-haem bond in vivo rather than affect enzyme or cofactor synthesis. Kinetics studies performed in vitro on brain tryptophan 5-hydroxylase showed that aflatoxin treatment in vivo increased the Km of the hydroxylase when L-tryptophan and synthetic 6,7-dimethyl-5,6,7,8-tetrahydrobiopterin were used as the substrate and cofactor, respectively. However, aflatoxin treatment did not alter the Vmax of tryptophan-5-hydroxylase.
D000348:Aflatoxins / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014365:Tryptophan Hydroxylase / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000378:metabolism*
D000348:Aflatoxins; D014366:Tryptophan Oxygenase; D014365:Tryptophan Hydroxylase