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Pioneers in the Early Years of Cytochrome P450 Research

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Abstract

Since the discovery of “cytochrome P450” in 1962, many biochemists have intensively studied various problems of this unique hemoprotein and contributed to the elucidation of its molecular properties and physiological functions. This review chapter describes the important contributions by the pioneer scientists in the early years of research on P450. A few important events that preceded and were pertinent to the discovery of P450 are also described.

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References

  • Appleby CA (1967) A soluble hemoprotein P-450 from nitrogen-fixing Rhizobium bacteroids. Biochim Biophys Acta 147:399–402

    Article  CAS  PubMed  Google Scholar 

  • Axelrod J (1955) The enzymatic deamination of amphetamine (Benzederine). J Biol Chem 214:753–763

    Google Scholar 

  • Claude A (1943) The constitution of protoplasm. Science 97:451–456

    Article  CAS  PubMed  Google Scholar 

  • Conney AH, Miller EC, Miller JA (1956) The metabolism of methylated aminoazo dyes. V. Evidence for induction of enzyme synthesis in the rat by 3-methylcholanthrene. Cancer Res 16:450–459

    CAS  PubMed  Google Scholar 

  • Conney AH, Davidson C, Gastel R, Burns JJ (1960) Adaptive increases in drug-metabolizing enzymes induced by phenobarbital and other drugs. J Pharmacol Exp Ther 130:1–8

    CAS  PubMed  Google Scholar 

  • Cooper DY, Estabrook RW, Rosenthal O (1963) The stoichiometry of C21 hydroxylation of steroids by adrenocortical microsomes. J Biol Chem 238:1320–1323

    CAS  PubMed  Google Scholar 

  • Cooper DY, Levin SS, Narasimhulu S, Rosenthal O, Estabrook RW (1965a) Photochemical action spectrum of the terminal oxidase of mixed function oxidase systems. Science 147:400–402

    Article  CAS  PubMed  Google Scholar 

  • Cooper DY, Narasimhulu S, Slade A, Raich W, Foroff O, Rosenthal O (1965b) Hemoprotein content and activity of solubilized steroid 11b-hydroxylase preparation from adrenocortical mitochondria. Life Sci 4:2109–2114

    Article  CAS  PubMed  Google Scholar 

  • Dawson JH, Trudell JR, Barth G, Linder RE, Bunnenberg E, Djerassi C, Chiang R, Hager LP (1976) Chloroperoxidase. Evidence for P-450 type heme environment from magnetic circular dichroism spectroscopy. J Am Chem Soc 98:3709–3710

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Estabrook RW, Hildebrandt AG, Baron J, Netter KJ, Leibman K (1971) A new spectral intermediate associated with cytochrome P-450 function in liver microsomes. Biochem Biophys Res Commun 42:132–139

    Article  CAS  PubMed  Google Scholar 

  • Fujii-Kuriyama Y, Mizukami Y, Kawajiri K, Sogawa K, Muramatsu M (1982) Primary structure of a cytochrome P-450: coding nucleotide sequence of phenobarbital-inducible cytochrome P-450 cDNA from rat liver. Proc Natl Acad Sci USA 79:2793–2797

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Haniu M, Armes LG, Tanaka M, Yasunobu KT, Shastry BS, Wagner GC, Gunsalus IC (1982) The primary structure of the monooxygenase cytochrome P450CAM. Biochem Biophys Res Commun 105:889–894

    Article  CAS  PubMed  Google Scholar 

  • Harding BW, Wong SH, Nelson DH (1964) Carbon monoxide-binding substances in rat adrenal. Biochim Biophys Acta 92:415–417

    CAS  PubMed  Google Scholar 

  • Hashimoto Y, Yamano T, Mason HS (1962) An electron spin resonance study of microsomal Fex. J Biol Chem 237:PC3843–PC3844

    CAS  Google Scholar 

  • Haugen DA, Coon MJ (1976) Properties of electrophoretically homogeneous phenobarbital-inducible and β-naphthoflavone-inducible forms of liver microsomal cytochrome P-450. J Biol Chem 251:7929–7939

    CAS  PubMed  Google Scholar 

  • Hayaishi O, Katagiri M, Rothberg S (1955) Mechanism of the pyrocatecase reaction. J Am Chem Soc 77:5450–5451

    Article  CAS  Google Scholar 

  • Hayano M, Lindberg MC, Dorfman RI, Hancock JEH, Doering WE (1955) On the mechanism of the C-11 β-hydroxylation of steroids. J Am Chem Soc 77:5450–5451

    Google Scholar 

  • Horecker BL (1950) Triphosphopyridine nucleotide-cytochrome c reductase in liver. J Biol Chem 183:593–605

    CAS  Google Scholar 

  • Huang MT, West SB, Lu AYH (1976) Separation, purification, and properties of multiple forms of cytochrome P-450 from the liver microsomes of phenobarbital-treated mice. J Biol Chem 251:4659–4665

    CAS  PubMed  Google Scholar 

  • Ichihara K, Kusunose E, Kusunose M (1973) Some properties of NADPH-cytochrome c reductase reconstitutively active in fatty acid ω-hydroxylation. Eur J Biochem 38:463–472

    Article  CAS  PubMed  Google Scholar 

  • Ichikawa Y, Yamano T (1967) Reconversion of detergent- and sulfhydryl reagent-produced P-420 to P-450 by polyols and glutathione. Biochem Biophys Acta 131:490–497

    CAS  PubMed  Google Scholar 

  • Imai Y, Sato R (1966) Substrate interaction with hydroxylase system in liver microsomes. Biochem Biophys Res Commun 22:620–626

    Article  CAS  PubMed  Google Scholar 

  • Imai Y, Sato R (1974) A gel-electrophoretically homogeneous preparation of cytochrome P-450 from liver microsomes of phenobarbital-treated rabbits. Biochem Biophys Res Commun 60:8–14

    Article  CAS  PubMed  Google Scholar 

  • Ishimura Y, Ullrich V, Peterson JA (1971) Oxygenated cytochrome P-450 and its possible role in enzymatic hydroxylation. Biochem Biophys Res Commun 42:140–146

    Article  CAS  PubMed  Google Scholar 

  • Ito A, Sato R (1968) Purification by means of detergents and properties of cytochrome b 5 from liver microsomes. J Biol Chem 243:4922–4930

    CAS  PubMed  Google Scholar 

  • Iyanagi T, Mason HS (1973) Some properties of hepatic reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase. Biochemistry 12:2297–2308

    Article  CAS  PubMed  Google Scholar 

  • Iyanagi T, Mason HS (1974) Redox properties of the reduced nicotinamide adenine dinucleotide phosphate-cytochrome P-450 and reduced nicotinamide dinucleotide-cytochrome b 5 reductase. Biochemistry 13:1701–1710

    Article  CAS  PubMed  Google Scholar 

  • Katagiri M, Ganguli BN, Gunsalus IC (1968) A soluble cytochrome P-450 functional in methylene hydroxylation. J Biol Chem 243:3543–3546

    CAS  PubMed  Google Scholar 

  • Kato R (1960) Induced increase of meprobamate metabolism in rats treated with phenobarbital orphenaglycodol. Med Exp 3:95–100

    CAS  Google Scholar 

  • Kimura T, Suzuki K (1965) Enzymatic reduction of non-heme iron protein (adrenodoxin) by reduced nicotinamide adenine dinucleotide phosphate. Biochem Biophys Res Commun 20:373–379

    Article  CAS  PubMed  Google Scholar 

  • Klingenberg M (1958) Pigments of rat liver microsomes. Arch Biochem Biophys 75:376–386

    Article  CAS  PubMed  Google Scholar 

  • Lu AYH, Coon MJ (1968) Role of hemoprotein P-450 in fatty acid ω-hydroxylation in a soluble enzyme system from liver microsomes. J Biol Chem 243:1331–1332

    CAS  PubMed  Google Scholar 

  • Lu AYH, Junk KW, Coon MJ (1969) Resolution of the cytochrome P-450-containing ω-hydroxylation system of liver microsomes into three components. J Biol Chem 244:3714–3721

    CAS  PubMed  Google Scholar 

  • Mason HS, Fowlks WL, Peterson E (1955) Oxygen transfer and electron transport by the phenolase complex. J Am Chem Soc 77:2914–2915

    Article  CAS  Google Scholar 

  • Miyake Y, Gaylor JL, Mason HS (1968) Properties of a submicrosomal particle containing P-450 and flavoprotein. J Biol Chem 243:5788–5797

    CAS  PubMed  Google Scholar 

  • Murakami K, Mason HS (1967) An electron resonance study of microsomal Fex. J Biol Chem 242:1102–1110

    CAS  PubMed  Google Scholar 

  • Narasimhulu S, Cooper DY, Rosenthal O (1965) Spectrophotometric properties of a triton-clarified steroid 21-hydroxylase system of adrenocortical microsomes. Life Sci 4:2102–2107

    Article  Google Scholar 

  • Narhi LO, Fulco AL (1986) Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium. J Biol Chem 261:7160–7169

    CAS  PubMed  Google Scholar 

  • Omura T (2005) Heme-thiolate proteins. Biochem Biophys Res Commun 338:404–409

    Article  CAS  PubMed  Google Scholar 

  • Omura T (2010) Structural diversity of cytochrome P450 enzyme system. J Biochem 147:297–306

    Article  CAS  PubMed  Google Scholar 

  • Omura T (2011) Recollection of the early years of the research on cytochrome P450. Proc Jpn Acad Series B 87:617–640

    Article  CAS  Google Scholar 

  • Omura T, Sato R (1962) A new cytochrome in liver microsomes. J Biol Chem 237:PC1375–PC1376

    Google Scholar 

  • Omura T, Sato R (1963) Fractional solubilization of hemoproteins and partial purification of carbon monoxide-binding cytochrome from liver microsomes. Biochem Biophys Acta 71:224–226

    Article  CAS  PubMed  Google Scholar 

  • Omura T, Sato R (1964a) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 239:2370–2378

    CAS  PubMed  Google Scholar 

  • Omura T, Sato R (1964b) The carbon monoxide-binding pigment of liver microsomes. II. Solubilization, purification, and properties. J Biol Chem 239:2379–2385

    CAS  PubMed  Google Scholar 

  • Omura T, Sato R, Cooper DY, Rosenthal O, Estabrook RW (1965) Function of cytochrome P-450 of microsomes. Fed Proc 24:1181–1189

    CAS  PubMed  Google Scholar 

  • Omura T, Sanders E, Estabrook RW, Cooper DY, Rosenthal O (1966) Isolation from adrenal cortex of a non-heme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase. Arch Biochem Biophys 117:660–673

    Article  CAS  Google Scholar 

  • Orrenius S, Erisson JLE, Ernster L (1965) Phenobarbital-induced synthesis of the microsomal drug-metabolizing enzyme system and its relationship to the proliferation of endoplasmic reticulum: a morphometric and biochemical study. J Cell Biol 25:627–639

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Palade GE, Siekevitz P (1956) Liver microsomes, an integrated morphological and biochemical study. J Biophys Biochem Cytol 2:171–198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Phillips AH, Langdon RG (1962) Hepatic triphosphopyridine nucleotide-cytochrome c reductase: isolation, characterization, and kinetic studies. J Biol Chem 237:2652–2660

    CAS  PubMed  Google Scholar 

  • Poulos TL, Finzel BC, Gunsalus IC, Wagner GC, Kraut J (1985) The 2.6-Ǻ crystal structure of Pseudomonas putida cytochrome P450. J Biol Chem 260:16122–16130

    CAS  PubMed  Google Scholar 

  • Remmer H (1959) Die Beschleunigung der Evipan Oxydation und der Methylierung von Methylaminoantipyrin durch Barbitrate. Arch Exp Pathol Pharmakol 237:296–307

    Article  CAS  Google Scholar 

  • Remmer H, Merker HJ (1963) Enzyminduktion und Vermehrung von endoplasmatischen Reticulum in der Leberzelle wahrend der Behandlung mit Phenobaribital (Luminal). Klin Wochenschr 41:276–283

    Article  CAS  PubMed  Google Scholar 

  • Remmer H, Schenkman J, Estabrook RW, Sasame H, Gillette J, Narasimhulu S, Cooper DY, Rosenthal O (1966) Drug interaction with hepatic microsomal cytochrome. Mol Pharmacol 2:187–190

    CAS  PubMed  Google Scholar 

  • Ryan KJ, Engel LL (1957) Hydroxylation of steroids at carbon 21. J Biol Chem 225:103–114

    CAS  PubMed  Google Scholar 

  • Ryan D, Lu AYH, Kawalek J, West SB, Levin W (1975) Highly purified cytochrome P-448 and P-450 from rat liver microsomes. Biochem Biophys Res Commun 64:1134–1141

    Article  CAS  PubMed  Google Scholar 

  • Schenkman JB, Remmer H, Estabrook RW (1967) Spectral studies of drug interaction with hepatic microsomal cytochrome. Mol Pharmacol 3:113–123

    CAS  PubMed  Google Scholar 

  • Stern JO, Peisach J (1974) A model compound study of the CO-adduct of cytochrome P-450. J Biol Chem 249:7495–7498

    CAS  PubMed  Google Scholar 

  • Strittmatter CF, Ball EG (1951) A hemochromogen component of liver microsomes. Proc Natl Acad Sci USA 38:19–25

    Article  Google Scholar 

  • Strittmatter P, Velick SF (1956a) A microsomal cytochrome reductase specific for diphosphopyridine nucleotide. J Biol Chem 221:277–286

    CAS  PubMed  Google Scholar 

  • Strittmatter P, Velick SF (1956b) The isolation and properties of microsomal cytochrome. J Biol Chem 221:253–264

    CAS  PubMed  Google Scholar 

  • Suzuki K, Kimura T (1965) An iron protein as a component of steroid 11β-hydroxylase complex. Biochem Biophys Res Commun 19:340–345

    Article  CAS  PubMed  Google Scholar 

  • Takemori S, Suhara K, Hashimoto S, Hashimoto M, Sato H, Gomi T, Katagiri M (1975) Purification of cytochrome P-450 from bovine adrenocortical mitochondria by an “aniline-Sepharose” and the properties. Biochem Biophys Res Commun 63:588–593

    Article  CAS  PubMed  Google Scholar 

  • Van der Hoeven TA, Haugen DA, Coon MJ (1974) Cytochrome P-450 purified to apparent homogeneity from phenobarbital-induced rabbit liver microsomes: catalytic activity and other properties. Biochem Biophys Res Commun 60:569–575

    Article  PubMed  Google Scholar 

  • Williams CH, Kamin H (1962) Microsomal triphosphopyridine nucleotide-cytochrome c reductase of liver. J Biol Chem 237:587–595

    CAS  PubMed  Google Scholar 

  • Yoshida Y, Aoyama Y, Kumaoka H, Kubota S (1977) A highly purified preparation of cytochrome P-450 from microsomes of anaerobically grown yeast. Biochem Biophys Res Commun 70:723–728

    Google Scholar 

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Correspondence to Tsuneo Omura .

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Omura, T. (2014). Pioneers in the Early Years of Cytochrome P450 Research. In: Yamazaki, H. (eds) Fifty Years of Cytochrome P450 Research. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54992-5_1

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