Activities of tryptophan-metabolizing enzymes in liver and brain of rats treated with aflatoxins

Abstract

Male Sprague-Dawley rats were treated ip twice daily for 10 days with mixed aflatoxins (10 μg/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 K m of the hydroxylase when l-trytophan 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 V max of tryptophan-5-hydroxylase.