2014, Number 3
<< Back Next >>
Rev Cubana Farm 2014; 48 (3)
Cytochrome P450 system and xenobiotic metabolism
Rodríguez GJC, Rodeiro GI
Language: Spanish
References: 31
Page: 495-507
PDF size: 667.66 Kb.
ABSTRACT
The organisms are constantly exposed to a wide array of xenobiotics. Cytochrome
P450 enzymes are involved in the phase I of xenobiotic metabolism, including
pharmaceuticals, and in endogenous biosynthetic functions through oxidation,
reduction reactions and hydrolysis. It is estimated that cytochrome P450 can
metabolize up to two-thirds of drugs present in humans and that the bulk of these
reactions occur in the liver. These enzymes are found in all biological domains.
More than 18 000 cytochrome P450 genes are currently known and arranged into
families and subfamilies on the basis of amino acid sequence identity percentage,
and this number increases each year as new genome sequences are reported. They
are a superfamily of monooxidase hemoproteins in the oxidase system with mixed
functions and found on the membranes of the smooth endoplasmic reticulum and in
the inner mitochondrial membrane. The diversity of reactions that catalyzes and its
extensive substrate specificity turn it into one of the most diverse and versatile
catalysts ever known and plays a critical role in biochemistry, pharmacology and
toxicology. A keyword search was performed in Pubmed and Medscape databases in
the last ten years. Websites related to cytochrome P450 research as databases
were also consulted. This updated review covered general aspects of cytochrome
P450, a brief history of the research on this enzyme and its standard nomenclature
system, and also described its multiplicity, its distribution in body organs and its
sub-cellular location, structure and function.
REFERENCES
Cutiño Rodríguez EMR. Defensa química y citocromo P450: relación con la defensa inmune. Rev Med UV. 2011 Jul-Dic:53-63.
Guengerich FR. Cytochromes P450. In: Azenbacher P, Zanger UM editors. Metabolism of Drugs and Other Xenobiotics. Germany: Wiley-VCH Verlag GmbH and Co. KGaA Weinheim; 2012. p. 27-66.
Klingerberg M. Pigments of rat liver microsomes. Arch Biochem Biophys. 1958;75:376-86.
Garfinkel D. Studies on pig liver microsomes. I. Enzymic and pigment composition of different microsomal fractions. Arch Biochem Biophys. 1958;77:493-509.
Omura T. Recollection of the early years of the research on cytochrome P450. Proc Jpn Acad Scr B Phys Biol Sci. 2011;87:617-40.
Singh D, Kashyap A, Pandey RV, Saini KS. Novel advances in cytochrome P450 research. Drug Discov Today. 2011;16:793-9.
Zhang T, Zhao M, Xie Z, He J, Liu LA, Wei DQ. Recent progress on bioinformatics, functional genomics, and metabolomics research of cytochrome P450 and its impact on drug discovery. Curr Top Med Chem. 2012;12:1346-55.
Mansuy D. Brief historical overview and recent progress on cytochromes P450: adaptation of aerobic organisms to their chemical environment and new mechanisms of prodrug bioactivation. An Pharm Fr. 2011;69:62-9.
Guengerich FP, Rendic S. Update information on drug metabolism systems 2009, part I. Curr Drug Metab. 2010;11:1-3.
McKinnon RA, Sorich MJ, Ward MB. Cytochrome P450, part 1: multiplicity and function. J Pharm Pract Re. 2008;38:55-7.
Guengerich FP, Munro AW. Unusual cytochrome P450 enzymes and reactions. J Biol Chem. 2013;288:17065-73.
Rendic S, Guengerich FP. Contributions of human enzymes in carcinogen metabolism. Chem Res Toxicol. 2012;25:1316-83.
Ortiz de Montellano P. Cytochrome P450: Structure, Mechanism, and Biochemistry. New York: Kluwer Academic/Plenum Publishers; 2005.
Hollenberg PF, Kent UM, Bumpus NN. Mechanism-based inactivation of human cytochromes p450s: experimental characterization, reactive intermediates, and clinical implications. Chem Res Toxicol. 2008;21:189-205.
Gallego-Fernández A. Generalidades del Citocromo P450. Aspectos fundamentales del citocromo P450. Madrid: Colección Docencia Universitaria; 2011. p. 7-32.
Poulos TL, Johnson EF. Structures of cytochrome P450 enzymes. In Cytochrome P450: Structure, Mechanism, and Biochemistry. Ortiz de Montellano PR. 3rd ed. New York: Kluwer Academic/Plenum Publishers; 2005. p. 87-114.
Nelson DR. Cytochrome P450s in humans. Human Genomics. 2009 [cited 2013 Sep 14];4:59-65. Available from: http://drnelson.utmem.edu/CytochromeP450.html
Sirim D, Widmann M, Wagner F, Pleiss J. Prediction and analysis of the modular structure of cytochrome P450 monooxygenases. BMC Struct. Biol. 2010;10:34.
Johnson EF, Stout CD. Structural diversity of eukaryotic membrane cytochrome P450s. J Biol Chem. 2013;288:17082-90.
Nelson DR. Progress in tracing the evolutionary paths of cytochrome P450. Biochim Biophys Acta Prot Proteom. 2011;1814:14-8.
Guengerich FP. New trends in cytochrome P450 research at the half-century mark. J Biol Chem. 2013;288:17063-4.
Ding X, Kaminsky LS. Human extrahepatic cytochromes P450: Function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu Rev Pharmacol Toxicol. 2003;43:149-73.
Sevior DK, Pelkonen O, Ahokas JT. Hepatocytes: the powerhouse of biotransformation. Int J Biochem Cell Biol. 2012;44:257-61.
Im SC, Waskell L. The interaction of microsomal cytochrome P450 2B4 with its redox partners, cytochrome P450 reductase and cytochrome b5. Arch Biochem Biophys. 2011;507:144-53.
Sim SC, Ingelman-Sundberg M. The Human Cytochrome P450 (CYP) Allele Nomenclature website: A peerreviewed database of CYP variants and their associated effects. Human Genomic. 2010;4:278-81.
Nelson DR. Comparison of P-450s from human and fugu: 420 million years of vertebrade P-450 evolution. Arch Biochem Biophys. 2003;409:18-24.
de Visser SP, Porro CS, Quesne MG, Sainna MA, Munro AW. Overview on theoretical studies discriminating the two-oxidant versus two-state-reactivity models for substrate monoxygenation by cytochrome P450 enzymes. Curr Top Med Chem. 2013;13:2218-32.
Krest CM, Onderko EL, Yosca TH, Calixto JC, Karp RF, Livada J, et al. Reactive intermediates in cytochrome P450 catalysis. J Biol Chem. 2013;288:17074-8.
Hannemann F, Bichet A, Ewen KM, Bernhardt R. Cytochrome P450 systemsbiological variations of electron transport chains. Biochim Biophys Acta. 2007;1770:330-344.
Capdevila JH, Faick JR, Harris RC. Cytochrome P-450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase. J Lipid Res. 2000,41:613-81.
Guengerich FP, Cheng Q. Orphans in the human cytochrome P450 family: approaches to discovering function and relevance to pharmacology. Pharmacol Rev. 2011;63:684-99.