Jedlitschky G, Cassidy A J, Sales M, Pratt N, Burchell B
Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
Biochem J. 1999 Jun 15;340 ( Pt 3)(Pt 3):837-43.
Xenobiotic metabolizing enzymes in the olfactory epithelium have been suggested to catalyse inactivation and facilitate elimination of odorants. We report here the molecular cloning and functional characterization of a human olfactory UDP-glucuronosyltransferase (UGT). The cloned protein is composed of 527 amino acids with an identity of 87% with a rat olfactory UGT and of 43-62% with other human UGT isoforms. Based on the sequence homology, it has been designated hUGT2A1. The gene was mapped to chromosome 4q13 by fluorescence in situ hybridization. The expression appeared to be specific for the olfactory tissue. The substrate specificity of this isoform was assessed using Chinese hamster V79 cells stably transfected with the isolated cDNA. The expressed enzyme showed a broad substrate spectrum including a range of phenolic compounds as well as aliphatic and monoterpenoid alcohols, among them many odorants. Furthermore, some steroids, especially androgens, some drugs and carcinogens were conjugated. The results support a role of the enzyme in olfactory perception and in protection of the neural system against airborne hazardous chemicals.
嗅觉上皮中的外源物代谢酶被认为可催化气味剂的失活并促进其消除。我们在此报告一种人类嗅觉UDP-葡萄糖醛酸基转移酶（UGT）的分子克隆及功能特性。克隆出的蛋白质由527个氨基酸组成，与大鼠嗅觉UGT的同源性为87%，与其他人类UGT同工型的同源性为43%-62%。基于序列同源性，它被命名为hUGT2A1。通过荧光原位杂交将该基因定位于染色体4q13。其表达似乎对嗅觉组织具有特异性。使用稳定转染了分离cDNA的中国仓鼠V79细胞评估了该同工型的底物特异性。表达的酶显示出广泛的底物谱，包括一系列酚类化合物以及脂肪族和单萜醇类，其中许多是气味剂。此外，一些类固醇，尤其是雄激素、一些药物和致癌物也能被结合。这些结果支持了该酶在嗅觉感知以及保护神经系统免受空气中有害化学物质影响方面的作用。
