GLUCURONIDATION - A DUAL CONTROL

1. Glucuronidation is a major detoxication process catalyzed by uridin e diphosphate glucuronosyltransferases. 2. The amount of enzyme can be modulated by numerous foreign compounds, such as common chemical indu cers already implicated in the induction of other detoxication enzymes . 3. Hormones such as thyroid hormones or growth hormone also are impl icated in the control of glucuronidation. 4. Because glucuronidation e nzymes (isozymes) are anchored in the endoplasmic reticulum membrane, with their active site likely being located on the lumenal side of the membrane, the membrane environment of these enzymes was shown to modu late their functional state as evaluated by the conjugating activity p er enzymatic molecular unit. 5. In accord with a first, previously pro posed model, it seems that this modulation can be attributed to differ ent conformational states of the enzymes, depending on the physicochem ical state of the membrane. 6. In accord with a second model, the memb rane may act as a barrier between the enzymes and the cosubstrate UDP- glucuronic acid, which is a polar and charged molecule synthesized in the cytosol. This would imply a transporting process for this molecule through the reticulum membrane, which has been characterized in vitro and could be of importance in vivo. 7. Glucuronidation is under the c ontrol of a dual regulation, by means of a specific isozyme expression level and by the modulation of their functional state. (C) 1998 Elsev ier Science Inc.