Abstract
Perhaps the beginning of the cytochrome P450 monooxygenase story should acknowledge the early compilation of knowledge of the metabolism of xenobiotics (compounds foreign to the body) by R.T. Williams in 1947 and the subsequent, much larger volume (Williams 1959). In those texts Williams described the many different metabolites produced from xenobiotics in vivo by animals and excreted by a variety of routes. It was a well-organized attempt to show metabolic pathways for handling compounds ingested by animals and recognized biochemical reactions as involved in metabolism. Brodie’s laboratory was one of the first to begin in vitro biochemical studies on xenobiotic metabolism, and from the latter part of the 1940s through the 1960s (Brodie et al. 1955) produced a stream of outstanding scientists who further led the field in the study of the oxidative enzymes of xenobiotic metabolism. From such studies, as well as work from Miller’s laboratory (Mueller and Miller 1953), it became clear that liver microsomes were the source of NADPH-dependent, oxidative enzymes capable of metabolizing a number of xenobiotic compounds. Since the 1950s more than 800 different xenobiotics, ranging from drugs to organic chemicals, have been found to be substrates for liver microsomal oxidative enzymes.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Ahlgren R, Simpson ER, Waterman MR, Lund J (1990) Characterization of the promoter/regulatory region of bovine CYP11A (P450 see) gene. J Biol Chem 265: 3313–3319
Alvares AP, Schilling G, Levin W, Kuntzman R (1967) Studies on the induction of CO-binding pigments in liver microsomes by phenobarbital and 3-methylcholanthrene. Biochem Biophys Res Commun 29: 521–526
Axelrod J (1955) The enzymatic demethylation of ephedrine. J Pharmacol Exp Ther 114: 430–438
Backes WL, Eyer CS (1989) Cytochrome P450 LM2 reduction: substrate effects on the rate of reductase-LM2 association. J Biol Chem 264: 6252–6259
Botelho LH, Ryan DE, Levin W (1979) Amino acid compositions and partial amino acid sequences of three highly purified forms of liver microsomal cytochrome P450 from rats treated with polychlorinated biphenyls, phenobarbital, or 3-methylcholanthrene. J Biol Chem 254: 5635–5640
Brodie BB, Axelrod J, Cooper JR, Gaudette LE, La Du BN, Mitowa C, Udenfriend S (1955) Detoxication of drugs and other foreign compounds by liver microsomes. Science 121: 603–604
Cheng KC, Schenkman JB (1982) Purification and characterization of two constitutive forms of rat liver microsomal cytochrome P450. J Biol Chem 257: 2378–2385
Cheng KC, Schenkman JB (1983) Testosterone metabolism by cytochrome P450 isozymes RLM3 and RLM5 and by microsomes. Metabolite identification. J Biol Chem 258: 11738–11744
Coon MJ, Vermillion KC, Vatsis KP, French JS, Dean WL, Haugen DA (1977) Biochemical studies on drug metabolism: isolation of multiple forms of liver microsomal cytochrome P450. In: Jerina DM (ed) Drug metabolism concepts. Washington, pp 46–71 (ACS Symposium Series, vol. 44 )
Diehl HL, Schadelin J, Ullrich V (1970) Studies on the kinetics of cytochrome P450 reduction in rat liver microsomes. Hoppe-Seyler’s Z Physiol Chem 351: 1359–1371
Estabrook RW, Cooper DY, Rosenthal O (1963) The light reversible carbon monoxide inhibition of the steroid C21-hydroxylase system of the adrenal cortex. Biochem Z 338: 741–755
Estabrook RW, Hildebrandt AG, Baron J, Netter KJ, Leibman K (1971) A new spectral intermediate associated with cytochrome P450 function in liver microsomes. Biochem Biophys Res Commun 42: 132–139
Fujii-Kuriyama Y, Mizukami Y, Kawajuri K, Sagawa K, Muramatsu M (1982) Primary structure of a cytochrome P450: coding nucleotide sequence of phenobarbital-inducible cytochrome P450 cDNA from rat liver. Proc Natl Acad Sci USA 79: 2793–2797
Funae Y, Imaoka S (1987) Purification and characterization of liver microsomal cytochrome P450 from untreated male rats. Biochim Biophys Acta 926: 349–358
Gigon PL, Gram TE, Gillette JR (1969) Studies on the rate of reduction of hepatic microsomal cytochrome P450 by reduced nicotinamide adenine dinucleotide phosphate: effect of substrate. Mol Pharmacol 5: 109–122
Gillette JR, Brodie BB, La Du BN (1957) The oxidation of drugs by liver microsomes: on the role of TPNH and oxygen. J Pharmacol Exp Ther 119: 532–540
Gorsky LD, Koop DR, Coon MJ (1984) On the stoichiometry of the oxidase and monooxygenase reaction catalyzed by liver microsomal cytochrome P450: products of oxygen reduction. J Biol Chem 259: 6812–6817
Hayaishi D, Nozaki M (1969) Nature and mechanisms of oxygenases. Science 164: 389–396
Hildebrandt AG, Roots I (1975) Reduced NADPH-dependent formation and breakdown of hydrogen peroxide during mixed function oxidation reactions in liver microsomes. Arch Biochem Biophys 171: 385–397
Holm KA, Kupfer D (1985) Isolation by ion-exchange high performance liquid chromatography of rabbit liver cytochrome P450 with regioselectivity for co-hydroxylation of prostaglandins. J Biol Chem 260: 2027–2030
Imai M, Shimada H, Watanabe Y, Malsushima-Higiya Y, Makino R, Koga H, Horiuchi T, Ishimura Y (1989) Uncoupling of the cytochrome P450 cam monooxygenase reaction by a single mutation, threonine-252 to alanine or valine: a possible role of the hydroxy amino acid in oxygen activation. Proc Natl Acad Sci USA 86: 7823–7827
Ishimura Y, Ullrich V, Peterson JA (1971) Oxygenated cytochrome P450 and its possible role in enzymic hydroxylation. Biochem Biophys Res Commun 42: 140–146
Jansson I, Schenkman JB (1987) Influence of cytochrome b5 on the stoichiometry of the different oxidative reactions catalyzed by liver microsomal cytochrome P450. Drug Metab Dispos 15: 344–348
Jansson I, Mole JE, Schenkman JB (1985) Purification and characterization of a new form (RLM2) of liver microsomal cytochrome P450 from untreated rat. J Biol Chem 260: 7084–7093
Jerina DM, Daly JW, Witkop B, Zaltzman-Nirenberg P, Udenfriend S (1970) 1,2-Naphthalene oxide as an intermediate in the microsomal hydroxylation of naphthalene. Biochemistry 9: 147–155
Johnson EF, Schwab GE (1984) Constitutive forms of rabbit liver microsomal cytochrome P450: enzymatic diversity, polymorphism and allosteric regulation. Xenobiotica 14: 3–18
Lambeth JD, Kriengsiri S (1985) Cytochrome P450scc-adrenodoxin interactions: ionic effects on binding and regulation of cytochrome reduction by bound steroid substrates. J Biol Chem 260: 8810–8816
Lindberg RLP, Negishi M (1989) Alteration of mouse cytochrome P450 coh substrate specificity by mutation of a single amino-acid residue. Nature 339: 632–634
Lu AYH, Coon MJ (1968) Role of hemoprotein P450 in fatty acid co-hydroxylation in a soluble enzyme from liver microsomes. J Biol Chem 243: 1331–1332
Lu AYH, Levin W (1972) Partial purification of cytochromes P450 and P448 from rat liver microsomes. Biochem Biophys Res Commun 46: 1334–1339
Mason HS (1957) Mechanisms of oxygen metabolism. Science 125: 1185–1188
Mason HS, North JC, Vanneste M (1965) Microsomal mixed-function oxidations: the metabolites of xenobiotics. Fed Proc 24: 1172–1180
Mathis JM, Houser WH, Bresnick E, Cidlowski JA, Hines RN, Prough RA, Simpson ER (1989) Glucocorticoid regulation of the rat cytochrome P450c (P4501A1) gene: receptor binding with intron 1. Arch Biochem Biophys 269: 93–105
Müller GC, Miller JA (1953) The metabolism of methylated aminoazo dyes: II. Oxidative demethylation by rat liver homogenates. J Biol Chem 202: 579–587
Nebert DW, Nelson DR, Coon MJ (1991) The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol 10: 1–14
Nordblom GD, White RE, Coon MJ (1976) Studies on hydroperoxide-dependent substrate hydroxylation by purified liver microsomal cytochrome P450. Arch Biochem Biophys 175: 524–533
Omura T, Sato R (1962) A new cytochrome in liver microsomes. J Biol Chem 237:PC1375–1376
Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes: I. Evidence for its hemoprotein nature. J Biol Chem 239: 2370–2378
Oprian DD, Coon MJ (1982) Reactions of oxygenated P450 LM4. In: Sato R, Kato R (eds) Microsomes, drug oxidation and drug toxicity. Wiley, New York, pp 139–145
Oprian DD, Vatsis KP, Coon MJ (1979) Kinetics of reduction of cytochrome P450 LM4 in a reconstituted liver microsomal enzyme system. J Biol Chem 254: 8895–8902
Parli CJ, McMahon RE (1973) The mechanism of microsomal deamination: heavy isotope studies. Drug Metab Dispos 1: 337–340
Peterson JA, Ebel RE, O’Keefe DH, Matsubara T, Estabrook RW (1976) Temperature dependence of cytochrome P450 reduction. J Biol Chem 251: 4010–4016
Peterson JA, White RE, Yasukochi Y, Coomes ML, O’Keefe DL, Ebel RE, Masters BSS, Ballou DP, Coon MJ (1977) Evidence that purified liver microsomal cytochrome P450 is a one-electron acceptor. J Biol Chem 252: 4431–4434
Posner HS, Mitoma C, Udenfriend S (1961a) Enzymatic hydroxylation of aromatic compounds: II. Further studies of the properties of the microsomal hydroxylating system. Arch Biochem Biophys 94: 269–279
Posner HS, Mitoma C, Rothberg S, Udenfriend S (1961b) Enzymic hydroxylation of aromatic compounds: III. Studies on the mechanism of microsomal hydroxylation. Arch Biochem Biophys 94: 280–290
Powis G, Jansson I (1982) Stoichiometry of the mixed function oxidase. In: Schenkman JB, Kupfer D (eds) Hepatic cytochrome P450 monooxygenase system. Pergamon, New York, pp 699–713
Rahimtula AD, O’Brien PJ (1974) Hydroperoxide catalyzed liver microsomal aromatic hydroxylation reactions involving cytochrome P450. Biochem Biophys Res Commun 60: 440–447
Schenkman JB (1982) Brief history of cytochrome P450. In: Schenkman JB, Kupfer D (eds) Hepatic cytochrome P450 monooxygenase system. Pergamon, New York, pp 1–5
Schenkman JB, Remmer H, Estabrook RW (1967) Spectral studies of drug interaction with hepatic microsomal cytochrome. Mol Pharmacol 3: 113–123
Schenkman JB, Sligar SG, Cinti DL (1982) Substrate interaction with cytochrome P450. In: Schenkman JB, Kupfer D (eds) Hepatic cytochrome P450 monooxygenase system. Pergamon, New York, pp 587–615
Schenkman JB, Tamburini PP, Jansson I, Epstein PM (1987) Interactions between cytochrome P450 and other components of the microsomal electron transfer system. In: Sato R, Omura T, Imai Y, Fujii-Kuriyama Y (eds) Cytochrome P450: new trends. Yamada conference XVII. Yamada Science Foundation, Japan, pp 59–64
Sladek NE, Mannering GJ (1966) Evidence for a new P-450 hemoprotein in hepatic microsomes from methylcholantrene treated rats. Biochem Biophys Res Commun 24: 668–674
Sligar SG (1976) Coupling of spin, substrate and redox equilibria in cytochrome P450. Biochemistry 15: 5399–5406
Sligar SG, Lipscomb JD, Debrunner PG, Gunsalus IC (1974) Superoxide anion production by the autoxidation of cytochrome P450 cam. Biochem Biophys Res Commun 61: 290–296
Sligar SG, Cinti DL, Gibson GG, Schenkman JB (1979) Spin state control of the hepatic cytochrome P450 redox potential. Biochem Biophys Res Commun 90: 925–932
Sogawa K, Fujisawa-Sehara, Yamane M, Fujii-Kuriyama (1986) Location of regulatory elements responsible for drug induction in the rat cytochrome P450c gene. Proc Natl Acad Sci USA 83: 8044–8048
Song BJ, Matsunaga T, Hardwick JP, Palk SS, Veech RL, Yang CS, Gelboin HV, Gonzalez FJ (1987) Stabilization of cytochrome P450 messenger ribonucleic acid in the diabetic rat. Mol Endocrinol 1: 542–547
Tamburini PP, White R, Schenkman JB (1985) Chemical characterization of protein-protein interactions between cytochrome P450 and cytochrome b5. J Biol Chem 260: 4007–4015
Ullrich V, Ruf HH, Wende P (1977) The structure and mechanism of cytochrome P450. Croat Chem Acta 49: 213–222
Uno T, Imai Y (1989) Identification of regions functioning in substrate interaction of rabbit liver cytochrome P450 ( Laurate (w-l)-hydroxylase ). J Biochem (Tokyo) 106: 569–574
White RE, Sligar SG, Coon MJ (1980) Evidence for a homolytic mechanism of peroxide oxygen-oxygen bond cleavage during substrate hydroxylation by cytochrome P450. J Biol Chem 255: 11108–11111
Whysner JA, Ramseyer J, Kazmi GM, Harding BW (1969) Substrate-induced spin state changes in cytochrome P450. Biochem Biophys Res Commun 36: 795–801
Williams RT (1959) Detoxication mechanism. Cunningham, London
Zhukov AA, Archakov AI (1982) Complete stoichiometry of free NADPH oxidation in liver microsomes. Biochem Biophys Res Commun 109: 813–818
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1993 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Schenkman, J.B. (1993). Historical Background and Description of the Cytochrome P450 Monooxygenase System. In: Schenkman, J.B., Greim, H. (eds) Cytochrome P450. Handbook of Experimental Pharmacology, vol 105. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77763-9_1
Download citation
DOI: https://doi.org/10.1007/978-3-642-77763-9_1
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-77765-3
Online ISBN: 978-3-642-77763-9
eBook Packages: Springer Book Archive