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  • 标题:Developmental aspects of xenobiotic transformation.
  • 作者:W Klinger ; D Muller
  • 期刊名称:Environmental Health Perspectives
  • 印刷版ISSN:0091-6765
  • 电子版ISSN:1552-9924
  • 出版年度:1976
  • 卷号:18
  • 页码:13
  • 语种:English
  • 出版社:OCR Subscription Services Inc
  • 摘要:In most laboratory animals monooxygenases are apparently absent or barely detectable in fetal organs until just before birth. In this contribution hepatic cytochrome P-450-dependent reactions in the rat are considered only. The results are interpreted on basis of the reaction scheme of Estabrook. To avoid methodological pitfalls the basic kinetics for all reactions investigated have been investigated with liver preparations from newborn and adult rats. The low monooxygenase activity of rat liver during the perinatal period can be observed even under optimal conditions for the in vitro enzyme assay. There are different developmental patterns for various reactions O-demethylation of codeine, phenazone-hydroxylation, first and second steps on N-demethylation of amidopyrine, N-demethylation of ethylmorphine. There are marked differences not only in Vmax but also in the postnatal development of Km and the inductibility by phenobarbital. Thus the existence of a different cytochrome P-450 is evident also by this approach. The low monooxygenase activity of rat liver during the perinatal period is not due to a lack of NADPH or NADH, to an age-dependent NADPH cytochrome P-450 reductase activity or to an age-dependent NADH-cytochrome P-450 reduction. Moreover this low activity is not due to an insufficient mitochondria-endoplasmic reticulum interaction. It is accompanied by low delta Amax after addition of a typical type I substrate (hexobarbital) and by a small amount of metyrapone-binding centers: it can be explained by a smaller percentage of active cytochrome P-450 in comparison to adult rat liver. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 13 14 15 16 17 18 19 20 21 22 23
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