The ontogeny of human drug-metabolizing enzymes: Phase I oxidative enzymes
The ontogeny of human drug-metabolizing enzymes: Phase I oxidative enzymes
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DOI：
10.1124/jpet.300.2.355
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发表时间：
2002-02-01
影响因子：
3.5
通讯作者：
McCarver, DG
中科院分区：
文献类型：
--
作者：
Hines, RN;McCarver, DG
虽然一些模式开始出现，但我们对人类I期药物代谢酶发育表达的了解仍远未完成。早在器官发生时就观察到表达，但这似乎仅限于少数酶。至少有两个在胎儿肝脏中表达的酶家族在围产期表现出时间转换（例如，CYP3A7到CYP3A4/3A5和FMO1到FMO3），而其他酶家族在妊娠期间表现出异构体表达的渐进式变化（例如，I类醇脱氢酶）。许多I期药物代谢酶表现出动态的围产期表达变化，这些变化主要由与出生有关的机制调节，其次是与成熟有关的机制。其中一些酶直到出生后才被检测到，这表明出生是必要的，但不是表达开始的充分条件（例如，CYP1A2）。组织特异性表达增加了个体发生过程中的复杂性。例如，CYP3A7的表达仅限于胎儿肝脏。然而，除了少数例外，开发过程中完整的时间关系信息是未知的。此外，大多数研究都集中在肝脏表达，而对肝外发育事件的了解甚少。
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.