Cloning and characterization of a novel human olfactory UDP-glucuronosyltransferase

被引:87
作者
Jedlitschky, G [1 ]
Cassidy, AJ [1 ]
Sales, M [1 ]
Pratt, N [1 ]
Burchell, B [1 ]
机构
[1] Univ Dundee, Ninewells Hosp & Med Sch, Dept Mol & Cellular Pathol, Dundee DD1 9SY, Scotland
基金
英国惠康基金;
关键词
airborne chemicals; detoxification; glucuronidation; olfactory enzymes;
D O I
10.1042/0264-6021:3400837
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:837 / 843
页数:7
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