Cytochrome P-450 Enzymes in Sterol Biosynthesis and Metabolism

  • Colin R. Jefcoate


The biosynthesis of sterols involves a series of both simple and complex cytochrome P-450-catalyzed monooxygenase reactions. These processes are generally distinguished from the multiplicity of reactions catalyzed by hepatic microsomal forms of P-450 by involving P-450 isozymes that exhibit a high degree of regio- and stereospecificity. The cell specificity of these monooxygenases has been noted in the previous chapter. In this chapter, we will examine the biochemical control of these steroidogenic cytochromes P-450. This is far more stringent than for the hepatic cytochromes P-450 because of the physiological importance of steroid hormones and bile acids. While the biosynthesis of these cytochromes is under hormonal control, this response takes a minimum of 12 hr for steroidogenic cytochromes P-450 (see Chapter 10). More common fluctuations in activity are required within minutes or hours. Here we will discuss the mechanisms of steroid hydroxylation and also some of the proposed mechanisms for rapid physiological control of steroidogenic enzymes.


Bile Acid Bile Acid Synthesis Sterol Biosynthesis Sterol Carrier Protein2 Kidney Mitochondrion 
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  1. 1.
    Lieberman, S., Greenfield, N. J., and Wolfson, A., 1984, A heuristic proposal for understanding steroidogenic processes, Endocr. Rev. 5: 128–148.PubMedCrossRefGoogle Scholar
  2. 2.
    Suzuki, K., and Kimura, T., 1965, An iron protein as a component of steroid 13- hydroxylase complex, Biochem. Biophys. Res. Commun. 19: 340–345.PubMedCrossRefGoogle Scholar
  3. 3.
    Chu, J. W., and Kimura, T., 1973, Studies on adrenal steroid hydroxylases: Molecular and catalytic properties of adrenodoxin reductase (a flavoprotein), J. Biol. Chem. 248: 2089–2094.PubMedGoogle Scholar
  4. 4.
    Lambeth, J. D., Seybert, D. W., Lancaster, J. R., Salerno, J. C., and Kamin, H., 1982, Steroidogenic electron transport in adrenal cortex mitochondria, Mol. Cell Biochem. 45: 13–31.PubMedCrossRefGoogle Scholar
  5. 5.
    Lambeth, J. D., and Kamin, H., 1976, Adrenodoxin reductase: Properties of the reduced enzyme with NADP ` and NADPH, J. Biol. Chem. 251: 4299–4306.PubMedGoogle Scholar
  6. 6.
    Light, D. R., and Walsh, C., 1980, Flavin analogs as mechanistic probes of adrenodoxin reductase-dependent electron transfer to the cholesterol side chain cleavage cytochrome P-450 of the adrenal cortex, J. Biol. Chem. 255: 4264–4277.PubMedGoogle Scholar
  7. 7.
    Lambeth, J. D., and Kamin, H., 1977, Adrenodoxin reductase and adrenodoxin: Mechanisms of reduction of ferricyanide and cytochrome c, J. Biol. Chem. 252: 2908–2917.PubMedGoogle Scholar
  8. 8.
    Chu, J. W., and Kimura, T., 1973, Studies on adrenal steroid hydroxylases: Complex formation of the hydroxylase components, J. Biol. Chem. 248: 5183–5187.PubMedGoogle Scholar
  9. 9.
    Lambeth, J. D., McCaslin, D. R., and Kamin, H., 1976, Adrenodoxin reductase adrenodoxin complex: Catalytic and thermodynamic properties, J. Biol. Chem. 251: 7545–7550.PubMedGoogle Scholar
  10. 10.
    Lambeth, J. D., and Kamin, H., 1979, Adrenodoxin reductase adrenodoxin complex: Flavin to iron-sulfur electron transfer as the rate limiting step in the NADPH-cytochrome c reductase reaction, J. Biol. Chem. 254: 2766–2774.PubMedGoogle Scholar
  11. 11.
    Lambeth, J. D., Seybert, D. W., and Kamin, H., 1979, Ionic effects on adrenal steroidogenic electron transport: The role of adrenodoxin as an electron shuttle, J. Biol. Chem. 254: 7255–7264.PubMedGoogle Scholar
  12. 12.
    Sheridan, R. P., Allen, L. C., and Carter, C. W., 1981, Coupling between oxidation state and hydrogen bond conformation in high potential iron-sulfur protein, J. Biol. Chem. 256: 5052–5057.PubMedGoogle Scholar
  13. 13.
    Lambeth, J. D., Lancaster, J. R., and Kamin, H., 1981, Adrenodoxin reductase adrenodoxin complex: Rapid formation and breakdown of the complex and a slow conformational change in the flavoprotein, J. Biol. Chem. 255: 4667–4672.Google Scholar
  14. 14.
    Lambeth, J. D., Lancaster, J. R., and Kamin, H., 1981, Steroidogenic electron transport by adrenodoxin reductase and adrenodoxin: Use of acetylated cytochrome c as a mechanistic probe of electron transfer, J. Biot Chem. 256: 3674–3678.Google Scholar
  15. 15.
    Hanukoglu, I., and Jefcoate, C. R., 1980, Mitochondria) cytochrome P-450,„: Mechanism of electron transport by adrenodoxin, J. Biol. Chem. 255: 3057–3061.PubMedGoogle Scholar
  16. 16.
    Lambeth, J. D., and Pember, S. 0., 1983, Cytochrome P-450sc, adrenodoxin complex: Reduction properties of the substrate-associated cytochrome and relation of the reduction states of heure and iron-sulfur centers to association of proteins, J. Biol. Chem. 258: 5596–5602.Google Scholar
  17. 17.
    Hanukoglu, I., Privalle, C. T., and Jefcoate, C. R., 1981, Mechanisms of ionic activation of adrenal mitochondrial cytochromes P-450,cc and P-45011p, J. Biol. Chem. 256: 4329–4335.PubMedGoogle Scholar
  18. 18.
    Lambeth, J. D., Seybert, D. W., and Kamin, H., 1980, Phospholipid vesicle-reconstituted cytochrome P-450,cc: Mutually facilitated binding of cholesterol and adrenodoxin, J. Biol. Chem. 255: 138–143.PubMedGoogle Scholar
  19. 19.
    Sligar, S. G., and Gunsalus, I. C., 1976, A thermodynamic model of regulation: Modulation of redox equilibria in camphor monoxygenase, Proc. Natl. Acad. Sci. USA 73: 1078–1082.PubMedCrossRefGoogle Scholar
  20. 20.
    Light, D. R., and Orme-Johnson, N. R., 1981, Beef adrenal cortical cytochrome P-which catalyzes the conversion of cholesterol to pregnenolone: Oxidation-reduction potentials of the free, steroid-complexed, and adrenodoxin-complexed P-450, J. Biol. Chem. 256: 343–350.PubMedGoogle Scholar
  21. 21.
    Hanukoglu, I., Spitsberg, V., Bumpus, J. A., Dus, K. M., and Jefcoate, C. R., 1981, Adrenal mitochondrial cytochrome P-450cc: Cholesterol and adrenodoxin interactions at equilibrium and during turnover, J. Biol. Chem. 256: 4321–4328.PubMedGoogle Scholar
  22. 22.
    Kido, T., and Kimura, T., 1979, The formation of binary and ternary complexes of cytochrome P-450,cc with adrenodoxin and adrenodoxin reductase adrenodoxin complex: The implication in ACTH function, J. Biol. Chem. 254: 11806–11815.PubMedGoogle Scholar
  23. 23.
    Burstein, S., Middleditch, B. S., and Gut, M., 1975, Mass spectrometric study of the enzymatic conversion of cholesterol to (22R)-22-hydroxycholesterol, (20R,22R)-20,22dihydroxycholesterol, and pregnenolone, and of (22R)-22-hydroxycholesterol to the glycol and pregnenolone in bovine adrenocortical preparations: Mode of oxygen incorporation, J. Biol. Chem. 250: 9028–9037.PubMedGoogle Scholar
  24. 24.
    Hume, R., Kelly, R. W., Taylor, P. L., and Boyd, G. S., 1984, The catalytic cycle of cytochrome P-450,cc and intermediates in the conversion of cholesterol to pregnenolone, Eur. J. Biochem. 140: 583–591.PubMedCrossRefGoogle Scholar
  25. 25.
    Orme-Johnson, N. R., Light, D. R., White-Stevens, R. W., and Orme-Johnson, W. H., 1979, Steroid binding properties of beef adrenal cortical cytochrome P-450 which catalyzes the conversion of cholesterol into pregnenolone, J. Biol. Chem. 254: 2103 2111Google Scholar
  26. 26.
    Paul, D. P., Gallant, S., Orme-Johnson, N. R., Orme-Johnson, W. H., and Brownie, A. C., 1976, Temperature dependence of cholesterol binding to cytochrome P-450,cc of the rat adrenal: Effect of adrenocorticotropic hormone and cycloheximide, J. Biol. Chem. 251: 7120–7126.PubMedGoogle Scholar
  27. 27.
    Jefcoate, C. R., Orme-Johnson, W. H.. and Beinert, H., 1976, Cytochrome P-450 of bovine adrenal mitochondria: Ligand binding to two forms resolved by EPR spectroscopy, J. Biol. Chem. 251: 3706–3715.PubMedGoogle Scholar
  28. 28.
    Jefcoate, C. R., Simpson, E. R., Boyd, G. S., Brownie, A. C., and Orme-Johnson, W. H., 1973, The detection of different states of the P-450 cytochromes in adrenal mitochondria: Changes induced by ACTH, Ann. N.Y. Acad. Sci. 212: 243.PubMedCrossRefGoogle Scholar
  29. 29.
    Jänig, G. R., Makower, A., Kraft, R., Rabe, H., and Ruckpaul, K., 1984, Identification of tyrosine as axial heure iron ligand in cytochrome P-450-LM2, Xenobiotica 14 (SI): 49.CrossRefGoogle Scholar
  30. 30.
    Jefcoate, C. R., 1977, Cytochrome P-450 of adrenal mitochondria: Steroid binding sites on two distinguishable forms of rat adrenal mitochondrial cytochrome P-450,cc, J. Biol. Chem. 252: 8788–8796.PubMedGoogle Scholar
  31. 31.
    Sheets, J. J., and Vickery, L. E., 1983, Active site-directed inhibitors of cytochrome P-450,cc: Structural and mechanistic implications of a side chain-substituted series of amino-steroids, J. Biol. Chem. 258: 11446–11452.PubMedGoogle Scholar
  32. 32.
    Greenfield, N. J., Gerolimatos, B., Szwergold, B. S., Wolfson, A. J., Prasad, V. V. K., and Lieberman S., 1981, Effects of phospholipid and detergent on the substrate specificity of adrenal cytochrome P-450,cc: Substrate binding and kinetics of cholesterol side chain oxidation, J. Biol. Chem. 256: 4407–4417.PubMedGoogle Scholar
  33. 33.
    Jefcoate, C. R., 1982, pH modulation of ligand binding to adrenal mitochondrial cytochrome P-450,c,, J. Biol. Chem. 257: 4731–4737.Google Scholar
  34. 34.
    Pember, S. O., Powell, G. L., and Lambeth, J. D., 1983, Cytochrome P-450scc—phospholipid interactions: Evidence for a cardiolipin binding site and thermodynamics of enzyme interactions with cardiolipin, cholesterol, and adrenodoxin, J. Biol. Chem. 258: 3198–3206.PubMedGoogle Scholar
  35. 35.
    Robinson, N. C., Strey, F., and Talbert, L., 1980, Investigation of the essential boundary layer phospholipids of cytochrome c oxidase using Triton X-100 delipidation, Biochemistry 19: 3656–3661.PubMedCrossRefGoogle Scholar
  36. 36.
    Larroque, C., and van Lier, J. E., 1983, Spectroscopic evidence for the formation of a transient species during cytochrome P-450,cc induced hydroperoxysterol—glycol conversions, Biochem. Biophys. Res. Commun. 112: 655–662.PubMedCrossRefGoogle Scholar
  37. 37.
    Sligar, S. G., Cinti, D. L., Gibson, G. G., and Schenkman, J. B., 1979, Spin state control of the hepatic cytochrome P450 redox potential, Biochem. Biophys. Res. Cornmun. 90: 925–932.CrossRefGoogle Scholar
  38. 38.
    Ristau, O., Rein, H., Greschner, S., Jänig, G.-R., and Ruckpaul, K.. 1979, Quantitative analysis of the spin equilibrium of cytochrome P-450 LM2 fraction from rabbit liver microsomes, Acta Biot Med. Ger. 38: 177–185.Google Scholar
  39. 39.
    Larroque, C., and van Lier, J. E., 1980, The subzero temperature stabilized oxyferro complex of purified cytochrome P-450,„x, FEBS Lett. 115: 175–177.PubMedCrossRefGoogle Scholar
  40. 40.
    Tuckey, R. C., and Kamin, H., 1983, Kinetics of 02 and CO binding to adrenal cytochrome P-450„«: Effect of cholesterol, intermediates, and phosphatidylcholine vesicles, J. Biol. Chem. 258: 4232–4237.PubMedGoogle Scholar
  41. 41.
    Mitani, F., Ilzuka, T., Ueno, R., lshimura, Y., Kimura. T., Izumi, S., Komatsu, N., and Watanabe, K., 1982, Regulation of cytochrome P450 activities in adrenocortical mitochondria from normal rats and human neoplastic tissues, Adv. Enzyme Regul. 20: 213–231.Google Scholar
  42. 42.
    Morohashi, K., Fujii-Kuriyama, Y., Okada, Y., Sogawa, K., Hirose, T.. Inayama, S., and Omura, T., 1984, Molecular cloning and nucleotide sequence of cDNA for mRNA of mitochondrial cytochrome P-450(SCC) of bovine adrenal cortex, Proc. Natl. Acad. Sci. USA 81: 4647–4651.Google Scholar
  43. 43.
    Chashchin, V. L., Vasilevsky, V. I., Shkumatov, V. M., and Akhrem, A. A., 1984, The domain structure of the cholesterol side-chain cleavage cytochrome P-450 from bovine adrenocortical mitochondria, Biochim. Biophys. Acta 787: 27–38.PubMedCrossRefGoogle Scholar
  44. 44.
    Ichikawa, Y., and Hiwatashi, A., 1982, The role of the sugar regions of components of the cytochrome P-450-linked mixed-function oxidase (monooxygenase) system of bovine adrenocortical mitochondria, Biochim. Biophys. Acta 705: 82–91.PubMedCrossRefGoogle Scholar
  45. 45.
    Sato, H., Ashida, N., Suhara, K., ltagaki, E.. Takemori, S., and Katagiri. M., 1978, Properties of an adrenal cytochrome P-450 (P-4501íp) for the hydroxylations of corticosteroids, Arch. Biochem. Biophys. 190: 307–314.Google Scholar
  46. 46.
    Momoi, K., Okamoto, M., Fujii, S.. Kim, C. Y., Miyake, Y., and Yamano T., 1983, 19-Hydroxylation of 18-hydroxy-I l-deoxycorticosterone catalyzed by cytochrome P-45011p of bovine adrenocortex, J. Biol. Chem. 258: 8855–8860.Google Scholar
  47. 47.
    Okamoto, M., Wada, A., Onishi, T., Nonaka, Y., and Yamano, T., 1984, Cytochrome P450110 catalyzes production of aldosterone from corticosterone, Sixth International Symposium on Microsomes and Drug Oxidations (Abstracts). Brighton, England, p. 18.Google Scholar
  48. 48.
    Watanuki, M., Tilley, B. E., and Hall. P. F., 1978, Cytochrome P-450 for I113- and 18-hydroxylase activities of bovine adrenocortical mitochondria: One enzyme of two?, Biochemistry 17: 127–130.PubMedCrossRefGoogle Scholar
  49. 49.
    Haning, R., Tait, S. A. S., and Tait, J. F.. 1970, In vitro effects of ACTH, angiotensins, serotonin and potassium on steroid output and conversion of corticosterone to aldosterone by isolated adrenal cells, Endocrinology 87: 1147–1167.Google Scholar
  50. 50.
    Kramer, R. E., Gallant, S., and Brownie, A. C., 1979, The role of cytochrome P-450 in the action of sodium depletion on aldosterone biosynthesis in rats, J. Biol. Chem. 254: 3953–3958.PubMedGoogle Scholar
  51. 51.
    Martsev, S. P., Bespalov, I. A., Chashchin, V. L., and Akhrem, A. A., 1982, Steroid 1113-hydroxylase system: Reconstitution and study of interactions among protein components, in: Cytochrome P-450: Biochemistry, Biophysics and Environmental Implications ( E. Hietanen, M. Laitinen, and O. Hänninen, eds.), Elsevier, Amsterdam, pp. 413–420.Google Scholar
  52. 52.
    Lambeth, J. D., Kamin, H., and Seybert, D. W., 1980, Phosphatidylcholine vesicle reconstituted cytochrome P-450,«: Role of the membrane in control of activity and spin state of the cytochrome, J. Biol. Chem. 255: 8282–8288.PubMedGoogle Scholar
  53. 53.
    Tuckey, R. C., and Kamin, H., 1982, Kinetics of the incorporation of adrenal cytochrome P-450,c, into phosphatidylcholine vesicles, J. Biol. Chem. 257: 2887–2893.PubMedGoogle Scholar
  54. 54.
    Kowluru, R. A. George, R., and Jefcoate, C. R., 1983, Polyphosphoinositide activation of cholesterol side chain cleavage with purified cytochrome P-450,cc, J. Biol. Chem. 258: 8053–8059.Google Scholar
  55. 55.
    Lombardo, A., Defaye, G., Guidicelli, C., Monnier, N., and Chambaz, E. M., 1982, Integration of purified adrenocortical cytochrome P-450110 into phospholipid vesicles, Biochem. Biophys. Res. Commun. 104: 1638–1645.PubMedCrossRefGoogle Scholar
  56. 56.
    Kimura, T., 1981. ACTH stimulation on cholesterol side chain cleavage activity of adrenocortical mitochondria, Mol. Cell. Biochem. 36: 105–122.PubMedCrossRefGoogle Scholar
  57. 57.
    Peron, F. G., and Tsang, C. P. W., 1969, Further studies on corticosteroidogenesis. VI. Pyruvate and malate supported steroid 1l13-hydroxylation in rat adrenal gland mitochondria, Biochim. Biophys. Acta 180: 445–458.PubMedCrossRefGoogle Scholar
  58. 58.
    Hall, P. F., 1972, A possible role for transhydrogenation in side-chain cleavage of cholesterol, Biochemistry 11: 2891–2897.PubMedCrossRefGoogle Scholar
  59. 59.
    Klimek, J., Boguslawski, W., and Zelewski, L., 1979, The relationship between energy generation and cholesterol side-chain cleavage reaction in the mitochondria from human term placenta, Biochim. Biophys, Acta 587: 362–372.Google Scholar
  60. 60.
    Stevens, V. L., Aw, T. Y., Jones, D. P., and Lambeth, J. D., 1984, Oxygen dependence of adrenal cortex cholesterol side chain cleavage: Implications in the rate-limiting steps in steroidogenesis, J. Biol. Chem. 259: 1174–1179.PubMedGoogle Scholar
  61. 61.
    Jefcoate, C. R., Simpson, E. R., and Boyd, G. S., 1974, Spectral properties of rat adrenal-mitochondrial cytochrome P-450, Eur. J. Biochem. 42: 539–551.PubMedCrossRefGoogle Scholar
  62. 62.
    Crivello, J. F., and Jefcoate, C. R., 1980. Intracellular movement of cholesterol in rat adrenal cells: Kinetics and effects of inhibitors, J. Biol. Chem. 255: 8144–8151.PubMedGoogle Scholar
  63. 63.
    Strauss, J. F., III, Schuler, L. A., Rosenblum, M. F., and Tanaka, T., 1981, Cholesterol metabolism by ovarian tissue, Adv. Lipid Res. 18: 99–157.PubMedGoogle Scholar
  64. 64.
    Cooke, B. A., Dix, C. J., Magee-Brown, R., Janszen, F. H. A., and van der Molen, H. J., 1981, Hormonal control of Leydig cell function, Adv. Cyclic Nucleotide Res. 14: 593–609.PubMedGoogle Scholar
  65. 65.
    DiBartolomeis, M. J., and Jefcoate, C. R., 1984, Characterization of the acute stimulation of steroidogenesis in primary bovine adrenal cortical cell cultures, J. Biol. Chem. 259: 10159–10167.PubMedGoogle Scholar
  66. 66.
    Simpson, E. R., McCarthy, J. L. and Peterson, J. A., 1978, Evidence that the cycloheximide-sensitive site of adrenocorticotropic hormone action is in the mitochondrion, J. Biol. Chem. 253: 3135–3139.PubMedGoogle Scholar
  67. 67.
    Gwynne, J. T., and Hess, B., 1980, The role of high density lipoproteins in rat adrenal cholesterol metabolism and steroidogenesis, J. Biol. Chem. 255: 10875–10883.PubMedGoogle Scholar
  68. 68.
    Nishikawa, T., Mikami, K., Saito, Y., Tamura, Y., and Kumagai, A., 1981, Studies on cholesterol esterase in the rat adrenal. Endocrinology 108: 932–936.PubMedCrossRefGoogle Scholar
  69. 69.
    Hall, P. F., 1984, The role of the cytoskeleton in hormone action, Can. J. Biochem. Cell Biol. 62: 653–665.PubMedCrossRefGoogle Scholar
  70. 70.
    Simpson, E. R., Jefcoate, C. R., Brownie, A. C., and Boyd, G. S., 1972, The effect of ether anaesthesia stress on cholesterol-side-chain cleavage and cytochrome P450 in rat-adrenal mitochondria, Eur. J. Biochem. 28: 442–450.PubMedCrossRefGoogle Scholar
  71. 71.
    Brownie, A. C., Simpson, E. R., Jefcoate, C. R., Boyd, G. S., Orme-Johnson, W. H., and Beinert, H., 1972, Effect of ACTH on cholesterol side-chain cleavage in rat adrenal mitochondria, Biochem. Biophys. Res. Commun. 46: 483–490.PubMedCrossRefGoogle Scholar
  72. 72.
    Jefcoate, C. R., and Orme-Johnson, W. H.. 1975, Cytochrome P-450 of adrenal mitochondria: In vitro and in vivo changes in spin states, J. Biol. Chem. 250: 4671–4677.PubMedGoogle Scholar
  73. 73.
    Williams-Smith, D. L. Simpson. E. R., Barlow, S. M., and Morrison, P. J., 1976, Electron paramagnetic resonance studies of cytochrome P-450 and adrenal ferredoxin in single whole rat adrenal glands: Effect of corticotropin, Biochim. Biophvs. Acta 449: 72–83.CrossRefGoogle Scholar
  74. 74.
    von Dippe, P. J., Tsao, K., and Harding, B. W., 1982, The effect of ether stress and cycloheximide treatment on cholesterol binding and enzyme turnover of adrenal cortical cytochrome P450,ee, J. Steroid Biochern. 16: 763–769.CrossRefGoogle Scholar
  75. 75.
    Privalle, C. T., Crivello, J. F., and Jefcoate, C. R., 1983, Regulation of intramitochondrial cholesterol transfer to side-chain cleavage cytochrome P-450 in rat adrenal gland, Proc. Natl. Acad. Sci USA 80: 702–706.PubMedCrossRefGoogle Scholar
  76. 76.
    Privalle, C. T., and Jefcoate, C. R., 1985, ACTH control of cholesterol side chain cleavage at adrenal mitochondrial cytochrome P-450,«: Regulation of intramitochondrial cholesterol transfer, J. Biol. Chem. submitted for publication.Google Scholar
  77. 77.
    Pederson, R. C., and Brownie, A. C., 1983, Cholesterol side-chain cleavage in the rat adrenal cortex: Isolation of a cycloheximide-sensitive activator peptide, Proc. Natl. Acad. Sci USA 80: 1882–1886.CrossRefGoogle Scholar
  78. 78.
    Vahouny, G. V., Chanderbhan, R., Noland, B. J.. Irwin, D.. Dennis, P., Lambeth, J. D., and Scallen, T. J., 1983, Sterol carrier protein2: Identification of adrenal sterol carrier protein2 and site of action for mitochondrial cholesterol utilization, J. Biol. Chem. 258: 11731–11737.PubMedGoogle Scholar
  79. 79.
    Krueger, R. J., and Orme-Johnson, N. R., 1983, Acute adrenocorticotropic hormone stimulation of adrenal corticosteroidogenesis: Discovery of a rapidly induced protein, J. Biol. Chem. 258: 10159–10167.PubMedGoogle Scholar
  80. 80.
    Simpson, E. R., 1979, Cholesterol side-chain cleavage, cytochrome P450, and the control of steroidogenesis, Mol. Cell. Endocrinol. 13: 213–227.PubMedCrossRefGoogle Scholar
  81. 81.
    Farese, R. V., 1984, Phospholipids as intermediates in hormone action, Mol. Cell. Endocrinol. 35: 1–14.PubMedCrossRefGoogle Scholar
  82. 82.
    Igarashi, Y., and Kimura, T., 1984, Adrenocorticotropic hormone-mediated changes in rat adrenal mitochondrial phospholipids, J. Biol. Chem. 259: 10745–10753.PubMedGoogle Scholar
  83. 83.
    Kominami, s., Hara, H., Ogishima, T., and Takemori, S., 1984, Interaction between cytochrome P-450 (P-450c21) and NADPH-cytochrome P-450 reductase from adrenocortical microsomes in a reconstituted system, J. Biol. Chem. 259: 2991–2999.PubMedGoogle Scholar
  84. 84.
    Kominami, S., and Takemori, S., 1982, Effect of spin state on reduction of cytochrome P-450 (P-450(221) from bovine adrenocortical microsomes, Biochim. Biophys. Acta 709: 147–153.PubMedCrossRefGoogle Scholar
  85. 85.
    Nakajin, s., Hall, P. F., and Onoda, M., 1981, Testicular microsomal cytochrome P450 for C21 steroid side chain cleavage: Spectral and binding studies, J. Biol. Chem. 256: 6134–6139.PubMedGoogle Scholar
  86. 86.
    Kominami, S., Shinzawa, K., and Takemori, S., 1982, Purification and some properties of cytochrome P-450 specific for steroid 17a-hydroxylation and C17—C21 bond cleavage from guinea pig adrenal microsomes, Biochem. Biophys. Res. Commun. 109: 916–921.PubMedCrossRefGoogle Scholar
  87. 87.
    Katagiri, M., Suhara, K., Shiroo, M., and Fujimura, Y., 1982, Role of cytochrome b5 in the cytochrome P-450-mediated C21-steroid 17,20-lyase reaction, Biochem. Biophys. Res. Commun. 108: 379–384.PubMedCrossRefGoogle Scholar
  88. 88.
    Takemori, S., Kominami, S., and Shinzawa, K., 1984, Studies on cytochrome P45017«.Iyase from guinea pig, in: International Union of Biochemistry Symposium 134 (Abstracts), Indian Institute of Science, Bangalore.Google Scholar
  89. 89.
    Onoda, M., and Hall, P. F., 1982, Cytochrome bs stimulates purified testicular microsomal cytochrome P-450 (C21 side-chain cleavage), Biochem. Biophvs. Res. Commun. 108: 454–460.CrossRefGoogle Scholar
  90. 90.
    Thompson, E. A., and Siiteri, P. K., 1974, Utilization of oxygen and reduced nicotinamide adenine dinucleotide phosphate by human placental microsomes during aromatization of androstenedione, J. Biol. Chem. 249: 5364–5372.PubMedGoogle Scholar
  91. 91.
    Meigs, R. A., and Ryan, K. J., 1968, Cytochrome P-450 and steroid biosynthesis in the human placenta, Biochem. Biophys. Acta 165: 476–482.PubMedCrossRefGoogle Scholar
  92. 92.
    Thompson, E. A., Jr., and Siiteri, P. K., 1974, The involvement of human placental microsomal cytochrome P-450 in aromatization, J. Biol. Chem. 249: 5373–5378.PubMedGoogle Scholar
  93. 93.
    Zachariah, P. K., and Juchau, M. R., 1977, Inhibition of placental mixed function oxidation with carbon monoxide: Reversal with monochromatic light, J. Steroid Biochem. 8: 221–228.PubMedCrossRefGoogle Scholar
  94. 94.
    Akhtar, M., Calder, M. R., Corina, D. L.. and Wright, J. N., 1982, Mechanistic studies on C-19 demethylation in oestrogen biosynthesis, Biochem. J., 201: 569–580.PubMedGoogle Scholar
  95. 95.
    Fishman, J., and Goto, H. L., 1982, Biochemical mechanism of aromatization, Cancer Res. (Suppl.) 42: 3277s - 3280s.Google Scholar
  96. 96.
    Caspi, E., Wicha, J., Arunachalam, T., Nelson, P., and Spiteller, G., 1984, Estrogen biosynthesis: Concerning the obligatory intermediacy of 20-hydroxy-100-formylandrost-4-ene-3,17-dione, J. Am. Chem. Soc. 106: 7282–7283.CrossRefGoogle Scholar
  97. 97.
    Reed, K. C., and Ohno, S., 1976, Kinetic properties of human placental aromatase: Application of an assay measuring 3H20 release from lgb,2gb-3H-androgens, J. Biol. Chem. 251: 1625–1631.PubMedGoogle Scholar
  98. 98.
    Osawa, Y., Tochigi, B., Higashiyama, T., Yarborough, C., Nakamura, T., and Yamamoto, T., 1982, Multiple forms of aromatase and response of breast cancer aromatase to antiplacental aromatase II antibodies, Cancer Res. (Suppl.) 42: 3299s - 3306s.Google Scholar
  99. 99.
    Fraser, D. R., 1980, Regulation of the metabolism of vitamin D, Physiol. Rev. 60: 551–613.PubMedGoogle Scholar
  100. 100.
    Larkins, R. G., Macanley, S. J., and Macintyre, I., 1975, Inhibitors of protein and RNA synthesis and 1,25-dihydroxycholecalciferol formation in vitro, Mol. Cell. Endocrinol. 2: 193–202.PubMedCrossRefGoogle Scholar
  101. 101.
    Horiuchi, N., Suda, T., Sasaki, S., Ogata, E., Ezawa, I., Sano, Y., and Shimazawa, E., 1975, The regulatory role of calcium in 25-hydroxycholecalciferol metabolism in chick kidney in vitro, Arch. Biochem. Biophys. 171: 540–548.PubMedCrossRefGoogle Scholar
  102. 102.
    Trzaskos, J. M., Bowen, W. D., Shafiee, A., Fischer, R. T., and Gaylor, J. L., 1984, Cytochrome P-450-dependent oxidation of lanosterol in cholesterol biosynthesis: Microsomal electron transport and C-32 demethylation, J. Biol. Chem. 259: 13402–13412.PubMedGoogle Scholar
  103. 103.
    Panini, S. R., Sexton, R. C., and Rudney, H., 1984, Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reduuctase by oxysterol by-products of cholesterol biosynthesis: Possible mediators of low density lipoprotein action, J. Biol. Chem. 259: 7767–7771.PubMedGoogle Scholar
  104. 104.
    Goad, L. J., 1984, Cholesterol biosynthesis and metabolism, in: Biochemistry of Steroid Hormones, 2nd ed. ( H. L. J. Makin, ed.), Blackwell, Oxford, pp. 20–70.Google Scholar
  105. 105.
    Danielsson, H., and Sjövall, J., 1975, Bile acid metabolism, Annu. Rev. Biochem. 44: 233–253.PubMedCrossRefGoogle Scholar
  106. 106.
    Mitropoulos, K. A., Balusubramanian, S., Gibbons, G. F., and Reeves, B. E. A., 1972, Diurnal variation in the activity of cholesterol 7a-hydroxylase in livers of fed and fasted rats, FEBS Lett. 27: 203–253.PubMedCrossRefGoogle Scholar
  107. 107.
    Kwok, C. T., Burnett, W., and Hardie, I. R., 1981, Regulation of rat liver microsomal cholesterol 7a-hydroxylase: Presence of a cytosolic activator, J. Lipid Res. 22: 570–579.PubMedGoogle Scholar
  108. 108.
    Gray, R. W., Omdahl, J. L., Ghazarian, J. G., and DeLuca, H. F., 1972, 25-Hydroxycholecalciferol-l-hydroxylase: Subcellular location and properties, J. Biol. Chem. 247: 7528–7532.Google Scholar
  109. 109.
    Pedersen, J. I., Björkhem, I., and Gustafsson, J., 1979, 26-Hydroxylation of C27-steroids by soluble liver mitochondrial cytochrome P-450, J. Biol. Chem. 254: 6464–6469.Google Scholar
  110. 110.
    Pedersen, J. I., Oftebro, H., and Vänngard, T., 1977, Isolation from bovine liver mitochondria of a soluble ferredoxin active in a reconstituted steroid hydroxylation reaction, Biochem. Biophys. Res. Commun. 76: 666–673.PubMedCrossRefGoogle Scholar
  111. 111.
    Pedersen, J. I., Ghazarian, J. G., Orme-Johnson, N. R., and DeLuca, H. F., 1976, Isolation of chick renal mitochondrial ferredoxin active in the 25-hydroxyvitamin D3la-hydroxylase system, J. Biol. Chem. 251: 3933–3941.PubMedGoogle Scholar
  112. 112.
    Björkhem, I., Holmberg, I., Oftebro, H., and Pedersen, J. I., 1980, Properties of a reconstituted vitamin D3 25-hydroxylase from rat liver mitochondria, J. Biol. Chem. 255: 5244–5249.PubMedGoogle Scholar
  113. 113.
    Ghazarian, J. G., Jefcoate, C. R., Knutson, J. C., Orme-Johnson. W. H., and DeLuca, H. F., 1974, Mitochondrial cytochrome 13450: A component of chick kidney 25-hydroxycholecalciferol-1 a-hydroxylase, J. Biol. Chem. 249: 3026–3033.Google Scholar
  114. 114.
    Warner, M., 1983, 25-Hydroxyvitamin D hydroxylation: Evidence for a dioxygenase activity of solubilized renal mitochondrial cytochrome P-450, J. Biol. Chem. 258: 115901 1593.Google Scholar
  115. 115.
    Ghazarian, J. G., and DeLuca, H. F., 1974, 25-Hydroxylase: A specific requirement for NADPH and a hemoprotein component in kidney mitochondria, Arch. Biochem. Biophys. 160: 63–72.Google Scholar
  116. 116.
    Hiwatashi, A., Nishii, Y., and Ichikawa, Y., 1982, Purification of cytochrome P-45001,, (25-hydroxyvitamin D3-la-hydroxylase) of bovine kidney mitochondria, Biochem. Biophys. Res. Commun. 105: 320–327.PubMedCrossRefGoogle Scholar
  117. 117.
    Niranjan, B. G., Wilson, N. M., Jefcoate, C. R., and Avadhani, N. G., 1984, Hepatic mitochondria) cytochrome P-450 system: Distinctive features of cytochrome P-450 involved in the activation of aflatoxin B1 and benzo(a)pyrene, J. Biol. Chem. 259: 12495–12501.PubMedGoogle Scholar
  118. 118.
    Hansson, R., and Wikvall, K., 1980, Hydroxylations in biosynthesis and metabolism of bile acids: Catalytic properties of different forms of cytochrome P-450, J. Biol. Chem. 255: 1643–1649.PubMedGoogle Scholar
  119. 119.
    Boström, H., 1983, Binding of cholesterol to cytochromes P-450 from rabbit liver microsomes, J. Biol. Chem. 258: 15091–15094.PubMedGoogle Scholar
  120. 120.
    Hansson, R., and Wikvall, K., 1982, Hydroxylations in biosynthesis of bile acids: Cytochrome P-450 LM4 and 12a-hydroxylation of 5ß-cholestane-3a,7a-diol, Eur. J. Biochem. 125: 423–429.PubMedCrossRefGoogle Scholar
  121. 121.
    Wikvall, K., 1984, Purification and properties of the cytochrome P450 species involved in bile acid biosynthesis, in: International Union of Biochemistry Symposium 134 ( Abstracts ), Bangalore, p. 134.Google Scholar
  122. 122.
    Goodwin, C. D., Cooper, B. W., and Margolis, S., 1982, Rat liver cholesterol 7ahydroxylase: Modulation of enzyme activity by changes in phosphorylation state, J. Biol. Chem. 257: 4469–4472.PubMedGoogle Scholar
  123. 123.
    Andersson, S., Holmberg, 1., and Wikvall, K., 1983, 25-Hydroxylation of C27-steroids and vitamin D3 by a constitutive cytochrome P-450 from rat liver microsomes, J. Biol. Chem. 258: 6777–6781.Google Scholar
  124. 124.
    Ryan, D. E., Iida, S., Wood, A. W., Thomas, P. E., Lieber, C. S., and Levin, W., 1984, Characterization of three highly purified cytochromes P450 from hepatic microsomes of adult male rats, J. Biol. Chem. 259: 1239–1250.PubMedGoogle Scholar
  125. 125.
    Johnson, E. F., and Schwab, G. E., 1984, Constitutive forms of rabbit-liver microsomal cytochrome P-450: Enzymatic diversity, polymorphism and allosteric regulation, Xenobiotica 14: 3–18.PubMedCrossRefGoogle Scholar
  126. 126.
    Aoyama, T., Imai, Y., and Sato, R., 1984, Hydroxylation of vitamin D3, prostaglandins and fatty acids by multiple forms of cytochrome P450 purified from rabbit liver microsomes, Sixth International Symposium on Microsomes and Drug Oxidations (Abstracts), Brighton, England, p. 44.Google Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Colin R. Jefcoate
    • 1
  1. 1.Department of PharmacologyUniversity of Wisconsin Medical SchoolMadisonUSA

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