传统的药物代谢主要以实验动物为对象进行药物早期及临床研究,近几年来,结合生物化学与分子生物学的发展,药物早期代谢研究进入到药物体外代谢的研究阶段,主要围绕人肝内参与代谢的细胞色素P450家族展开.本文就近年来对此家族酶的异源表达及其在药物代谢中的应用进行了综述.
[1] Nelson DR.. Comparison of P450s from human and fugu: 420 million years of vertebrate P450 evolution [J]. Archives of Biochemistry and Biophysics 2003, 1(1).
[2] LARSON J R, COOM M J, PORTER T D. Purification and properties of a shortened form of cytochrome P450 2E1:Deletion of the NH2-terminal membrane insertion signal peptide does not alter the catalytic activities [J]. Proceedings of the National Academy of Sciences of the United States of America 1991, 88.
[3] BARNES H J, ARLOTTO M P, WATERMAN M R. Expression and enzymatic activity of recombinant cytochrome P450 17-hydroxylase in Escherichia coli [J]. Proceedings of the National Academy of Sciences of the United States of America 1991, 88.
[4] SUEYOSHI T, PARK L J. Molecular engineering of microsomal CYP 2a-4 to a stable, watersoluble enzyme [J]. Archives of Biochemistry and Biophysics 1995, 322(10).
[5] WADA A, MATHEW P A, BARNES H J. Expression of functional bovine cholesterol side chain cleavage cytochrome P450(P450scc) in Escherichia coli [J]. Archives of Biochemistry and Biophysics 1991, 290(02).
[6] SAKAKI K, OEDA K. Monooxygenase activity of Saccharomyces cerevisiae cells transformed with expression plasmids carrying rat cytochrome P-450MC cDNA [J]. Journal of Biochemistry 1986, 99(03).
[7] GONZLEZ F J, KORZEKWA K R. Cytochromes expression systems [J]. Annual Review of Pharmacology and Toxicology 1995, 35(04).
[8] Toshiyuki Sakaki, Kuniyo Inouye. Practical Application of mammalian Cytochrome P450 [J]. Journal of Bioscience and Bioengineering 2000, 6(6).
[9] PEYRONNEAU M A, RENAUD J P. Optimization of yeast-expressed human liver cytochrome P450 3A4 catalytic activities by coexpressing NADPH-cytochrome P450 reductase and cytochrome b5 [J]. European Journal of Biochemistry 1992, 207(01).
[10] ALAIN H, MARC M, DANIELE W. Partial recoding of P450 and P450 Reductase cDNAs for improved expression in yeast and plants [J]. Methods in Enzymology 2002, 357(04).
[11] Masimirembwa CM, Otter C, Berg M, Jonsson M, Leidvik B, Jonsson E, Johansson T, Backman A, Edlund A, Andersson TB. Heterologous expression and kinetic characterization of human cytochromes P-450: validation of a pharmaceutical tool for drug metabolism research. [J]. Drug Metabolism and Disposition: The Biological Fate of Chemicals 1999, 10(10).
[12] GROGAN J, SHOU M G, ANDRUSIAK E A. Cytochrome P450 2A1, 2E1, and 2C9 cDNA-expression by insect cells and partial purification using hydrophobic chromatography [J]. Biochemical Pharmacology 1995, 50(09).
[13] Sawada M, Kamataki T. Genetically engineered cells stably expressing cytochrome P450 and their application to mutagen assays. [J]. Mutation Research: International Journal on Mutagenesis, Chromosome Breakage and Related Subjects 1998, 1(1).
[14] Shimada T, Tsumura F, Yamazaki H. Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. [J]. Drug Metabolism and Disposition: The Biological Fate of Chemicals 1999, 11(11).
[15] Bort R, Mace K, Boobis A, Gomez Lechon-MJ, Pfeifer A, Castell J. Hepatic metabolism of diclofenac: role of human CYP in the minor oxidative pathways. [J]. Biochemical Pharmacology 1999, 5(5).
[16] IRINA E K, EUGENE Y. Transgenic yeast expressing human cytochrome P450s can serve as a tool in studies of the mechanisms of their induction by various effectors [J]. Biochemical and Biophysical Research Communications 1996, 221(01).