Advertisement

Essential Features of NADH Dependent Cytochrome b5 Reductase and Cytochrome b5 of Liver and Lung Microsomes

  • Emel Arinç
Part of the NATO ASI Series Advanced Science Institutes Series book series (NSSA, volume 202)

Abstract

Endoplasmic reticulum of mammalian liver cells contains two major electron transport chains. One of these is NADH dependent where the reducing equivalents are transfered from NADH to cytochrome b5 through a flavoprotein, cytochrome b5 reductase. The second system is NADPH dependent and the reducing equivalents are transfered from NADPH to cytochrome P450 through cytochrome P450 reductase containing one mole each of FAD and FMN. NADH dependent cytochrome b5 system catalyzes several reactions of lipid metabolism such as Δ 9 desaturation of stearyl-CoA to oleyl-CoA while the NADPH dependent cytochrome P450 system participates monooxygenation of xenobiotics and of some endogenous compounds (1–5). Recently, these two pathways have been found to be interrelated and transfer of electrons from one pathway to another has been implicated as shown in Fig. 1. If cytochrome b5 acts as a link between these two electron transport systems, it is possible that there is such a regulation depending on availability of NADH and NADPH.

Keywords

Liver Microsome Phospholipid Vesicle Heme Binding Microsomal Cytochrome Hydrophobic Peptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    N. Oshino, Y. Imai, and R. Sato, A function of cytochrome b5 in fatty acid desaturation by rat liver microsomes, J. Biochenu (Tokyo) 69:155–167 (1971).Google Scholar
  2. 2.
    N. Oshino and T. Omura, Immunochemical evidence for the participation of cytochrome b5 in microsomal stearyl CoA desaturase reaction, Arch. Biochem. Biophys. 157:395–404 (1973).PubMedCrossRefGoogle Scholar
  3. 3.
    P. Strittmatter, L. Spatz, D. Corcoran, M. J. Rogers, B. Setlow, and R. Redline, Purification and properties of rat liver microsomal stearyl coenzyme A desaturase, Proc. Natl. Acad. Sci. USA 71:4565–4569 (1974).PubMedCrossRefGoogle Scholar
  4. 4.
    A. Y. H. Lu and S. B. West, Multiplicity of mammalian microsomal cytochrome P-450, Pharmac. Rev. 31:277–295 (1980).Google Scholar
  5. 5.
    S. D. Black and M. J. Coon, Comparative structures of P-450 cytochromes, in: “Cytochrome P-450. Structure, Mechanism and Biochemistry”, P. R. Ortiz de Montellano, ed., Plenum Press, New York (1986).Google Scholar
  6. 6.
    R. M. Philpot, E. Armç, and J. R. Fouts, Reconstitution of the rabbit pulmonary microsomal mixed-function oxidase system from solubilized components, Drug Metab. Dispos. 3:118–126 (1975).PubMedGoogle Scholar
  7. 7.
    E. Annç and R. M. Philpot, Preparation and properties of partially purified pulmonary cytochrome P-450 from rabbits, J. Biol. Chem. 251:3213–3220 (1976).Google Scholar
  8. 8.
    E. Arinç and M. Y. işcan, Comparative studies of sheep liver and lung microsomal aniline 4-hydroxylase, Comp. Biochem. Physiol. 74C:151–158 (1983).Google Scholar
  9. 9.
    E. Arinç, Characterization of sheep liver and lung microsomal ethylmorphine N-demethylase, Comp. Biochem. Physiol. 80B:389–399 (1985).Google Scholar
  10. 10.
    Z. Parandoosh, V. S. Fujita, M. J. Coon, and R. M. Philpot, Cytochrome P-450 isozymes 2 and 5 in rabbit lung and liver: comparison of structure and inducibility, Drug Metab. Dispos. 15:59–67 (1987).PubMedGoogle Scholar
  11. 11.
    Y. Kikuta, E. Kusunose, S. Matsubara, Y. Funae, S. Imaoka, I. Kubota, and M. Kusunose, Purification and characterization of hepatic microsomal prostaglandin w-hydroxylase cytochrome P-450 from pregnant rabbits, J. Biochem. (Tokyo) 106:468–473 (1989).Google Scholar
  12. 12.
    T. Güray and E. Armç, Purification of NADH-cytochrome b5 reductase from sheep lung and its electrophoretic spectral and some other properties, Int. J. Biochem. In Press.Google Scholar
  13. 13.
    T. C. Lee, R. C. Baker, and N. Stephens, Evidence for participation of cytochrome b5, in microsomal Δ.6-desaturation of fatty acids, Fedn. Proc. 36:672 (1977).Google Scholar
  14. 14.
    N. Oshino, Cytochrome b5 and its physiological significance, in: “Hepatic Cytochrome P-450 Monooxygenase System”, J. B. Shenkman and D. Kupfer, eds., Pergamon Press, New York (1980).Google Scholar
  15. 15.
    F. Paltauf, R. A. Prough, B. S. S. Masters, and J. M. Johnson, Evidence for the participation of cytochrome b5 in plasmalogen sysnthesis, J. Biol. Chem. 249:2661–2662 (1974).Google Scholar
  16. 16.
    E. L. Pugh and M. Kates, Direct saturation of eicosatrienoyl lecithin to arachidonyl lecithin by rat liver microsomes, J. Biol. Chem. 252:68–73 (1977).PubMedGoogle Scholar
  17. 17.
    S. R. Keyes, J. A. Alfano, I. Jansson, and D. L. Cinti, Rat liver microsomal elongation of fatty acids; possible involvement of cytochrome b5, J. Biol. Chem. 254:7778–7784 (1979).PubMedGoogle Scholar
  18. 18.
    V. V. R. Reddy, D. Kupfer, and E. Kaspi, Mechanism of C-5 double bond introduction in the biosynthesis of cholesterol by rat liver microsomes. Evidence for the participation of microsomal cytochrome b5, J. Biol. Chem. 252:2797–2801 (1977).PubMedGoogle Scholar
  19. 19.
    F. F. Kadlubar, E. M. McKee, and D. M. Ziegler, Reduced Pyridine nucleotide-dependent N-hydroxylamine oxidase and reductase activities of hepatic microsomes, Arch. Biochem. Biophys. 156:46–57 (1973).PubMedCrossRefGoogle Scholar
  20. 20.
    F. F. Kadlubar and D. M. Ziegler, Properties of a NADH-dependent N-hydroxylamine reductase isolated from pig liver microsomes, Arch. Biochem. Biophys. 169:83–92 (1974).CrossRefGoogle Scholar
  21. 21.
    D. E. Hultquist and P. G. Passon, Catalysis of methemoglobin reduction by erythrocyte cytochrome b5 and cytochrome b5 reductase, Nature 229:252–254 (1971).CrossRefGoogle Scholar
  22. 22.
    T. L. Poulos and A. G. Mauk, Models of complexes formed between cytochrome b5 and subunits of methemoglobin, J. Biol. Chem. 258:7369–7373 (1983).PubMedGoogle Scholar
  23. 23.
    N. Borgese, G. Pietrini, and S. Gaetani, Concentration of NADH-cytochrome b5, reductase in erythrocytes of normal and methemoglobinemic individuals measured with a quantitative radioimmunoblotting assay, J. Clin. Inves. 80:1296–1302 (1987).CrossRefGoogle Scholar
  24. 24.
    H. Fukushima, G. F. Grinstead, and J. L. Gaylor, Total enzymic synthesis of cholesterol from lanosterol: cytachrome b5-dependence of 4-methyl sterol oxidase, J. Biol. Chem. 256:4822–4826 (1981).PubMedGoogle Scholar
  25. 25.
    P. Strittmatter, E. T. Machuga, and G. J. Roth, Reduced Pyridine nucleotides and cytochrome b5 as electron donors for prostaglandin synthetase reconstituted in dimyristyl phosphatidylcholine vesicles, J. Biol Chem. 257:11883–11886 (1982).PubMedGoogle Scholar
  26. 26.
    N. Dippenaar, J. Booyens, D. Fabbri, and I. E. Katzeff, The reversibility of cancer: Evidence that malignancy in melanoma cells is gamma-linolenic acid deficiency-dependent, S. Afr. Med. J. 62:505–509 (1982).PubMedGoogle Scholar
  27. 27.
    Y. Imai, The roles of cytochrome b5 in reconstituted monooxygenase systems containing various forms of hepatic microsomal cytochrome P-450, J. Biochem. (Tokyo) 89:351–362 (1981).Google Scholar
  28. 28.
    E. T. Morgan and M. J. Coon, Effects of cytochrome b5 on cytochrome P-450 catalyzed reactions, Drug Metab. Dispos. 12:358–364 (1984).PubMedGoogle Scholar
  29. 29.
    I. Jansson, P. P. Tamburini, L. V. Favreau, and J. B. Schenkman, The interaction of cytochrome b5 with four cytochrome P-450 enzymes from the untreated rat, Drug Metab. Dispos. 13:453–458 (1985).PubMedGoogle Scholar
  30. 30.
    J. A. Peterson and R. A. Prough, Cytochrome P-450 reductase and cytochrome b5 in cytochrome P-450 catalysis, in: “Cytochrome P-450. Structure, Mechanism and Biochemistry”, P. R. Ortiz de Montellano, ed., Plenum Press, New York (1986).Google Scholar
  31. 31.
    P. Strittmatter and S. F. Velick, The isolation and properties of microsomal cytochrome, J. Biol. Chem. 221:253–264 (1956).PubMedGoogle Scholar
  32. 32.
    S. F. Velick and P. Strittmatter, The oxidation reduction stoichiometry and potential of microsomal cytochrome, J. Biol. Chem. 221:265–275 (1956).PubMedGoogle Scholar
  33. 33.
    P. Strittmatter and S. F. Velick, The purification and properties of microsomal cytochrome reductase, J. Biol. Chem. 228:785–799 (1957).PubMedGoogle Scholar
  34. 34.
    B. Hagihara, E. Furuyo, and T. Sugiyama, Chemical and Physical properties of cytochrome b5, in: “Hepatic Cytochrome P-450 Monooxygenase System”, J. B. Schenkman and D. Kupfer, eds., Pergamon Press, New York (1980).Google Scholar
  35. 35.
    P. Strittmatter and H. A. Dailey, Essential structural features and orientation of cytochrome b5 in membranes, in: “Membranes and Transport Vol.1”, A. N. Martonosi, ed., Plenum Press, New York (1982).Google Scholar
  36. 36.
    J. Ozols and P. Strittmatter, Correction of amino acid sequence of calf liver microsomal cytochrome b5, J. Biol. Chem. 244:6617–6618 (1969).PubMedGoogle Scholar
  37. 37.
    L. Spatz and P. Strittmatter, A form of cytochrome b5 that contains an additional hydrophobic sequence of 40 amino acid residues, Proc. Nat. Acad. Sci. USA 65:1042–1046 (1971).CrossRefGoogle Scholar
  38. 38.
    P. J. Fleming, H. A. Dailey, D. Corcoran, and P. Strittmatter, The primary structure of the nonpolar segment of bovine cytochrome b5, J. Biol. Chem. 253:5369–5372 (1978).PubMedGoogle Scholar
  39. 39.
    J. Ozols, Structure of cytochrome b5 and its topology in the microsomal membrane, Biochim. Biophys. Acta 997:121–130 (1989).PubMedCrossRefGoogle Scholar
  40. 40.
    J. Ozols, C. Gerard, and F. G. Nobrega, Proteolytic cleavage of horse liver cytochrome b5, J. Biol. Chem. 251:6767–6774 (1976).PubMedGoogle Scholar
  41. 41.
    J. Ozols and C. Gerard, Covalent structure of the membranous segment of horse cytochrome b5, J. Biol.Chem. 252:8549–8553 (1977).PubMedGoogle Scholar
  42. 42.
    A. Tsugita, M. Kobayashi, S. Tani, S. Kyo, M. A. Rashid, Y. Yoshida, T. Kajihara, and B. Hagihara, Comparative study of the primary structures of cytochrome b5 from four species, Proc. Acad. Sci. USA 67:442–447 (1970).CrossRefGoogle Scholar
  43. 43.
    K. Kondo, S. Tajima, R. Sato, and K. Narita, Primary structure of membrane binding segment of cytochrome b5, J. Biochem. (Tokyo) 86:1119–1128 (1979).Google Scholar
  44. 44.
    F. S. Mathews, P. Argos, and M. Levine, The structure of cytochrome b5, at 2.0 Å resolution, Cold Spring Harbor Symp. Quant. Biol. 36:387–395 (1971).CrossRefGoogle Scholar
  45. 45.
    F. S. Mathews, E. W. Czerwinski, and P. Argos, The X-ray crystallographic structure of calf liver cytochrome b5, in: “The Porphryrins Vol VII”, D. Dolphin, ed., Academic Press, New York (1979).Google Scholar
  46. 46.
    J. Ozols and P. Strittmatter, The reactivity of lysyl residues of cytochrome b5, J. Biol. Chem. 241: 4793-4797 (1966).Google Scholar
  47. 47.
    P. Strittmatter, The nature of heme binding in microsomal cytochrome b5, J. Biol. Chem. 235:2492–2497 (1960).PubMedGoogle Scholar
  48. 48.
    T. E. Huntley and P. Strittmatter, The reactivity of the tyrosyl residues of cytochrome b5, J. Biol. Chem. 247:4648–4653 (1972).PubMedGoogle Scholar
  49. 49.
    H. A. Dailey and P. Strittmatter, Modification and identification of cytochrome b5, carboxyl groups involved in protein protein interactions with cytochrome b5 reductase, J. Biol. Chem. 254:5388–5396 (1979).PubMedGoogle Scholar
  50. 50.
    M. Y. işcan and E. Arinç, Kinetic and structural properties of biocatalytically active sheep lung microsomal NADPH-cytochrome c reductase, Int. J. Biochem. 18:731–741 (1986).PubMedCrossRefGoogle Scholar
  51. 51.
    O. Adali and E. Arinç, Characterization of sheep lung cytochrome P-450 isozymes 2, in: “Cytochrome P-450, Biochemistry and Biophysics”, I. Schuster, ed., Taylor and Francis, London (1989).Google Scholar
  52. 52.
    O. Adali and E. Arinç, Electrophoretic, spectral, catalytic and immunochemical properties of highly purified cytochrome P-450 from sheep lung, Int. J. Biochem. In Press.Google Scholar
  53. 53.
    S. Takesue and T. Omura, Solubilization of NADH cytochrome b5, reductase from liver microsomes by digestion, J. Biochem. (Tokyo) 67:259–266 (1970).Google Scholar
  54. 54.
    L. Spatz and P. Strittmatter, A form of reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase containing both the catalytic site and additional hydrophobic membrane binding segment, J. Biol. Chem. 248:793–799 (1973).PubMedGoogle Scholar
  55. 55.
    K. Mihara and R. Sato, Partial purification of NADH-cytochrome be reductase from rabbit liver microsomes with detergents and its properties, J. Biochem. (Tokyo) 71:725–735 (1972).Google Scholar
  56. 56.
    K. Mihara and R. Sato, Purification and properties of the intact form of NADH-cytochrome b5, reductase from rabbit liver microsomes, J. Biochem. (Tokyo) 78:1057–1073 (1975).Google Scholar
  57. 57.
    D. A. Schafer and D. E. Hultquist, Purification of bovine liver microsoal NADH-cytochrome b5 reductase using affinity chromatography, Biochem. Biophys. Acta 95:381–387 (1980).Google Scholar
  58. 58.
    J. Ozols, G. Korza, F. S. Heinemann, M. A. Hediger, and P. Strittmatter, Complete amino acid sequence of steer liver microsomal NADH-cytochrome b5 reductase, J. Biol. Chem. 260:11953–11961 (1985).PubMedGoogle Scholar
  59. 59.
    T. Yubisui, T. Miyata, S. Iwanaga, M. Tamura, and M. Takeshita, Complete amino acid sequence of NADH-cytochrome b5 reductase purified from human erythrocytes, J. Biochem. (Tokyo) 99:407–422 (1986).Google Scholar
  60. 60.
    T. Yubisui, Y. Naitoh, S. Zenno, M. Tamura, M. Takeshita and Y. Sakaki, Molecular cloning of cDNAs of human liver and placenta NADH-cytochrome b5 reductase, Proc. Natl. Acad. Sci. USA 84:3609–3613 (1987).PubMedCrossRefGoogle Scholar
  61. 61.
    K. Miki, S. Kaida, N. Kasai, T. Iyanagi, K. Kobayashi, and K. Hayashi, Crystallization and preliminary X-ray crystallographic study of NADH-cytochrome b5 reductase from pig liver microsomes, J. Biol. Chem. 262:11801–11802 (1987).PubMedGoogle Scholar
  62. 62.
    P. Strittmatter, The properties of nucleotide complexes with microsomal cytochrome reductase, J. Biol. Chem. 234:2665–2669 (1959).PubMedGoogle Scholar
  63. 63.
    P. Strittmatter, The interaction of nucleotides with microsomal cytochrome reductase, J. Biol. Chem. 233: 748-753 (1958).Google Scholar
  64. 64.
    A. Loverde and P. Strittmatter, The role of lysyl residues in the structure and reactivity of cytochrome b5 reductase, J. Biol. Chem. 243:5779–5787 (1968).PubMedGoogle Scholar
  65. 65.
    C. S. Hackett and P. Strittmatter, Covalent cross linking of the active sites of vesicle-bound cytochrome b5 and NADH-cytochrome b5 reductase, J. Biol. Chem. 259:3275–3282 (1984).PubMedGoogle Scholar
  66. 66.
    C. S. Hackett, W. B. Novoa, J. Ozols, and P. Strittmatter, Identification of the essential cysteine residue of NADH-cytochrome be reductase, J. Biol. Chem. 261:9854–9857 (1986).PubMedGoogle Scholar
  67. 67.
    T. Güray, Purification and spectral and catalytical characterization of NADH-cytochrome b5 reductase from lung microsomes, Ph.D. Thesis, Middle East Technical University, Ankara (1989).Google Scholar
  68. 68.
    C. R. Kensil and P. Strittmatter, Binding and fluorescence properties of the membrane domain of NADH-cytochrome be reductase, J. Biol. Chem. 261: 7316-7321 (1986).Google Scholar
  69. 69.
    M. J. Rogers and P. Strittmatter, The binding of reduced nicotine amide adenine dinucleotide-cytochrome b5 reductase to hepatic microsomes, J. Biol. Chem. 249: 5565–5569 (1974).PubMedGoogle Scholar
  70. 70.
    D. E. Koppel, P. J. Fleming, and P. Strittmatter, Intramembrane positions of membrane bound chromophores determined by excitation energy transfer, Biochemistry 24:5450–5457 (1979).CrossRefGoogle Scholar
  71. 71.
    P. J. Fleming, D. E. Koppel, A. L. Y. Lau, and P. Strittmatter, Intramembrane position of the fluorescent tryptophanyl resideu in membrane bound cytochromes, Biochemistry 24:5458–5464 (1979).CrossRefGoogle Scholar
  72. 72.
    H. A. Dailey and P. Strittmatter, Structural and functional properties of the membrane binding segment of cytochrome b5, J. Biol. Chem. 253:8203–8209 (1978).PubMedGoogle Scholar
  73. 73.
    H. A. Dailey and P. Strittmatter, The role of COOH terminal anionic residues in binding cytochrome b5 to phospholipid vesicles and biological membranes, J. Biol. Chem. 256:1677–1680 (1981).PubMedGoogle Scholar
  74. 74.
    H. G. Enoch, P. J. Fleming, and P. Strittmatter, The binding of cytochrome b5, to phospholipid vesicles and biological membranes: effect of orientation on intermembrane transfer and digestion by carboxypeptidase Y, J. Biol. Chem. 254:6483–6488 (1979).PubMedGoogle Scholar
  75. 75.
    C. Tanford, The Hydrophobic Effect, pp.205–211, John Wiley and Sons, New York (1980).Google Scholar
  76. 76.
    S. Tajima and R. Sato, Topological studies of the membrane binding segment of cytochrome b5 embedded in phosphatidylcholine vesicles, J. Biocnem. (Tokyo) 87:123–134 (1980).Google Scholar
  77. 77.
    H. A. Dailey and P. Strittmatter, Orientation of the carboxyl and NH2 termini of the membrane binding segment of cytochrome b5 on the same side of phospholipid bilayers, J. Biol. Chem. 256:3951–3955 (1981).PubMedGoogle Scholar
  78. 78.
    Y. Takagaki, R. Radhakrishnan, K. W. A. Wirtz, and H. G. Khorana, The membrane embedded segment of cytochrome b5 as studied by cross linking with photoactive phospholipids. II. The nontransferable form, J. Biol. Chem. 258:9136–9142 (1983).PubMedGoogle Scholar
  79. 79.
    E. P. Gogol, D. M. Engelman, and G. Zaccai, Neutron diffrection analysis of cytochrome b5 reconstituted in deuterated lipid multilayers, Biophys. J. 43:285–292 (1983).PubMedCrossRefGoogle Scholar
  80. 80.
    E. P. Gogol and D. M. Engelman, Neutron scattering shows that cyctochrome b5, penetrates deeply into the lipid bilayer, Biophys. J. 46:491–495 (1984).PubMedCrossRefGoogle Scholar
  81. 81.
    L. M. Rzepecki, P. Strittmatter, and L. G. Herbette, X-ray diffraction analysis of cytochrome b5 reconstituted in egg phosphatidylcholine vesicles, Biophys. J. 49:829–838 (1986).PubMedCrossRefGoogle Scholar
  82. 82.
    E. Arinç, L. M. Rzepecki, and P. Strittmatter, Topography of the C-terminus of cytochrome b5 tightly bound to dimyristoylphosphatidylcholine vesicles, J. Biol. Chem. 262:15563–15567 (1987).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Emel Arinç
    • 1
  1. 1.Joint Graduate Program in Biochemistry Department of BiologyMiddle East Technical UniversityAnkaraTurkey

Personalised recommendations