Molecular biology of bilirubin metabolism.
As the genes encoding the glucuronidating enzymes are discovered, it is evident that glucuronidation is a magnificent example of how in evolution, man became adapted to his "intoxicating" environment. A superfamily of genes is necessary to dispose of the toxins and carcinogens that are encountered by inhalation and ingestion. The enzymes that glucuronidate endogenous compounds are members of this large family. For the clinician, it is important to remember that jaundice may sometimes be the result of interactions at the level of bilirubin glucuronidation. When jaundice results from inactivation of members of the UGT1 family, conjugation of certain phenols, such as the anesthetic propofol, or synthetic estrogens, such as ethinylestradiol, can also be impaired. In the case of severe bilirubin glucuronidation deficiencies, such as the Crigler Najjar syndrome type I, there are exciting prospects for a possible cure by gene therapy.
Jansen
P L
PL
Division of Gastrointestinal and Liver Diseases, University Hospital, Groningen, The Netherlands.
Bosma
P J
PJ
Chowdhury
J R
JR
D000818:Animals; D001663:Bilirubin / Q000378:metabolism*; D003001:Cloning, Molecular; D003414:Crigler-Najjar Syndrome / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy; D014453:Glucuronosyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D016031:Liver Transplantation; D008954:Models, Biological; D008967:Molecular Biology; D009154:Mutation; D051381:Rats; D011911:Rats, Gunn
D018076:DNA, Complementary; D014453:Glucuronosyltransferase; D001663:Bilirubin