The ontogeny of human drug-metabolizing enzymes: phase I oxidative enzymes.
Although some patterns are beginning to emerge, our knowledge of human phase I drug-metabolizing enzyme developmental expression remains far from complete. Expression has been observed as early as organogenesis, but this appears restricted to a few enzymes. At least two of the enzyme families that are expressed in the fetal liver exhibit a temporal switch in the immediate perinatal period (e.g., CYP3A7 to CYP3A4/3A5 and FMO1 to FMO3), whereas others show a progressive change in isoform expression through gestation (e.g., the class I alcohol dehydrogenases). Many of the phase I drug-metabolizing enzyme exhibit dynamic perinatal expression changes that are regulated primarily by mechanisms linked to birth and secondarily to maturity. A few of these enzymes are not detectable until well after birth, suggesting that birth is necessary but not sufficient for the onset of expression (e.g., CYP1A2). Tissue-specific expression adds to the complexity during ontogeny. For example, CYP3A7 expression is restricted to the fetal liver. However, with few exceptions, complete temporal relationship information during development is not known. Furthermore, most studies have concentrated on hepatic expression and much less is known about extrahepatic developmental events.
Hines
Ronald N
RN
Birth Defects Research Center, Department of Pediatrics, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226-4801, USA. rhines@mcw.edu
McCarver
D Gail
DG
D000375:Aging / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D000426:Alcohol Dehydrogenase; D008995:Monoamine Oxidase