The cytochrome P450 superfamily: Biochemistry, evolution and drug metabolism in humans

被引:573
作者
Danielson, PB [1 ]
机构
[1] Univ Denver, Dept Biol Sci, Denver, CO 80210 USA
关键词
D O I
10.2174/1389200023337054
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cytochrome P450s comprise a superfamily of heme-thiolate proteins named for the spectral absorbance peak of their carbon-monoxide-bound species at 450 nm. Having been found in every class of organism, including Archaea, the P450 superfamily is believed to have originated from an ancestral gene that existed over 3 billion years ago. Repeated gene duplications have subsequently given rise to one of the largest of multigene families. These enzymes are notable both for the diversity of reactions that they catalyze and the range of chemically dissimilar substrates upon which they act. Cytochrome P450s support the oxidative, peroxidative and reductive metabolism of such endogenous and xenobiotic substrates as environmental pollutants, agrochemicals, plant allelochemicals, steroids, prostaglandins and fatty acids. In humans, cytochrome P450s are best know for their central role in phase I drug metabolism where they are of critical importance to two of the most significant problems in clinical pharmacology: drug interactions and interindividual variability in drug metabolism. Recent advances in our understanding of cytochrome P450-mediated drug metabolism have been accelerated as a result of an increasing emphasis on functional genomic approaches to P450 research. While human cytochrome P450 databases have swelled with a flood of new human sequence variants, the functional characterization of the corresponding gene products has not kept pace. In response researchers have begun to apply the tools of proteomics as well as homology-based and ab initio modeling to salient questions of cytochrome P450 structure/function. This review examines the latest advances in our understanding of human cytochrome P450s.
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页码:561 / 597
页数:37
相关论文
共 347 条
[1]  
ABDELRAZZAK Z, 1993, MOL PHARMACOL, V44, P707
[3]   Functional analysis of six different polymorphic CYP1B1 enzyme variants found in an Ethiopian population [J].
Aklillu, E ;
Oscarson, M ;
Hidestrand, M ;
Leidvik, B ;
Otter, C ;
Ingelman-Sundberg, M .
MOLECULAR PHARMACOLOGY, 2002, 61 (03) :586-594
[4]   Drug interactions with grapefruit juice [J].
Ameer, B ;
Weintraub, RA .
CLINICAL PHARMACOKINETICS, 1997, 33 (02) :103-121
[5]   SEQUENCE AND ORGANIZATION OF THE HUMAN MITOCHONDRIAL GENOME [J].
ANDERSON, S ;
BANKIER, AT ;
BARRELL, BG ;
DEBRUIJN, MHL ;
COULSON, AR ;
DROUIN, J ;
EPERON, IC ;
NIERLICH, DP ;
ROE, BA ;
SANGER, F ;
SCHREIER, PH ;
SMITH, AJH ;
STADEN, R ;
YOUNG, IG .
NATURE, 1981, 290 (5806) :457-465
[6]   GENERATION OF PROTEIN ISOFORM DIVERSITY BY ALTERNATIVE SPLICING - MECHANISTIC AND BIOLOGICAL IMPLICATIONS [J].
ANDREADIS, A ;
GALLEGO, ME ;
NADALGINARD, B .
ANNUAL REVIEW OF CELL BIOLOGY, 1987, 3 :207-242
[7]  
[Anonymous], PEROXIDASES CHEM BIO
[8]   5 OF 12 FORMS OF VACCINIA VIRUS-EXPRESSED HUMAN HEPATIC CYTOCHROME-P450 METABOLICALLY ACTIVATE AFLATOXIN-B1 [J].
AOYAMA, T ;
YAMANO, S ;
GUZELIAN, PS ;
GELBOIN, HV ;
GONZALEZ, FJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (12) :4790-4793
[9]   Induction of multidrug resistance-1 and cytochrome P450 mRNAs in human mononuclear cells by rifampin [J].
Asghar, A ;
Gorski, JC ;
Haehner-Daniels, B ;
Hall, SD .
DRUG METABOLISM AND DISPOSITION, 2002, 30 (01) :20-26
[10]   RIBOSOME GYMNASTICS - DEGREE OF DIFFICULTY 9.5, STYLE 10.0 [J].
ATKINS, JF ;
WEISS, RB ;
GESTELAND, RF .
CELL, 1990, 62 (03) :413-423