Cloning and characterization of a novel human olfactory UDP-glucuronosyltransferase.
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.
Jedlitschky
G
G
Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK.
Cassidy
A J
AJ
Sales
M
M
Pratt
N
N
Burchell
B
B
D000438:Alcohols / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D014453:Glucuronosyltransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D009830:Olfactory Bulb / Q000201:enzymology*; D009928:Organ Specificity; D010636:Phenols / Q000378:metabolism; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013256:Steroids / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
D000438:Alcohols; D007527:Isoenzymes; D010636:Phenols; D012333:RNA, Messenger; D013256:Steroids; D014453:Glucuronosyltransferase