GLUTATHIONE S-TRANSFERASES IN RAT OLFACTORY EPITHELIUM - PURIFICATION, MOLECULAR-PROPERTIES AND ODORANT BIOTRANSFORMATION

The olfactory epithelium is exposed to a variety of xenobiotic chemica ls, including odorants and airborne toxic compounds. Recently, two nov el, highly abundant, olfactory-specific biotransformation enzymes have been identified: cytochrome P-450olf1 and olfactory UDP-glucuronosylt ransferase (UGT(olf)). The latter is a phase II biotransformation enzy me which catalyses the glucuronidation of alcohols, thiols, amines and carboxylic acids. Such covalent modification, which markedly affects lipid solubility and agonist potency, may be particularly important in the rapid termination of odorant signals. We report here the identifi cation and characterization of a second olfactory phase II biotransfor mation enzyme, a glutathione S-transferase (GST). The olfactory epithe lial cytosol shows the highest GST activity among the extrahepatic tis sues examined. Significantly, olfactory epithelium had an activity 4-7 times higher than in other airway tissues, suggesting a role for this enzyme in chemoreception. The olfactory GST has been affinity-purifie d to homogeneity, and shown by h.p.l.c. and N-terminal amino acid sequ encing to constitute mainly the Yb1 and Yb2 subunits, different from m ost other tissues that have mixtures of more enzyme classes. The ident ity of the olfactory enzymes was confirmed by PCR cloning and restrict ion enzyme analysis. Most importantly, the olfactory GSTs were found t o catalyse glutathione.conjugation of several odorant classes, includi ng many unsaturated aldehydes and ketones, as well as epoxides. Togeth er with UGT(olf), olfactory GST provides the necessary broad coverage of covalent modification capacity, which may be crucial for the acuity of the olfactory process.