Odorant signal termination by olfactory UDP glucuronosyl transferase

THE onset of olfactory transduction has been extensively studied1–7, but considerably less is known about the molecular basis of olfactory signal termination6,8,9. It has been suggested that the highly active cytochrome P450 monooxygenases of olfactory neuroepithelium10–12 are termination enzymes5,8,11,12, a notion supported by the identification and molecular cloning of olfactory-specific cytochrome P450s (refs. 13–16). But as reactions catalysed by cytochrome P450 (refs 17, 18) often do not significantly alter volatility, lipophilicity or odour properties9,11, cytochrome P450 may not be solely responsible for olfactory signal termination. In liver and other tissues, drug hydroxylation by cytochrome P450 is frequently followed by phase II biotransformation, for example by UDP glucuronosyl transferase (UGT), resulting in a major change of solubility and chemical properties19. We report here the molecular cloning and expression of an olfactory-specific UGT. The olfactory enzyme, but not the one in liver microsomes, shows preference for odorants over standard UGT substrates. Furthermore, glucuronic acid conjugation abolishes the ability of odorants1,20 to stimulate olfactory adenylyl cyclase. This, together with the known broad spectrum of drug-detoxification enzymes17,19, supports a role for olfactory UGT in terminating diverse odorant signals.

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