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. 1992 Nov 15;288(Pt 1):15–17. doi: 10.1042/bj2880015

Brain nitric oxide synthase is a haemoprotein.

P Klatt 1, K Schmidt 1, B Mayer 1
PMCID: PMC1132072  PMID: 1280109

Abstract

Brain nitric oxide (NO) synthase showed pyridine haemochrome spectra typical of ferroprotoporphyrin IX-containing enzymes. The haem content of purified NO synthase was in the range 0.7-0.9 mol/mol of 160 kDa subunit. In the presence of CO, NO, KCN and miconazole, the L-citrulline-forming activity of NO synthase was markedly diminished, demonstrating that enzyme-bound haem is involved in enzymic NO synthesis.

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Selected References

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  1. Andronik-Lion V., Boucher J. L., Delaforge M., Henry Y., Mansuy D. Formation of nitric oxide by cytochrome P450-catalyzed oxidation of aromatic amidoximes. Biochem Biophys Res Commun. 1992 May 29;185(1):452–458. doi: 10.1016/s0006-291x(05)81006-x. [DOI] [PubMed] [Google Scholar]
  2. Berry E. A., Trumpower B. L. Simultaneous determination of hemes a, b, and c from pyridine hemochrome spectra. Anal Biochem. 1987 Feb 15;161(1):1–15. doi: 10.1016/0003-2697(87)90643-9. [DOI] [PubMed] [Google Scholar]
  3. Boucher J. L., Genet A., Vadon S., Delaforge M., Mansuy D. Formation of nitrogen oxides and citrulline upon oxidation of N omega-hydroxy-L-arginine by hemeproteins. Biochem Biophys Res Commun. 1992 May 15;184(3):1158–1164. doi: 10.1016/s0006-291x(05)80004-x. [DOI] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  5. Bredt D. S., Ferris C. D., Snyder S. H. Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites. J Biol Chem. 1992 Jun 5;267(16):10976–10981. [PubMed] [Google Scholar]
  6. Bredt D. S., Hwang P. M., Glatt C. E., Lowenstein C., Reed R. R., Snyder S. H. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature. 1991 Jun 27;351(6329):714–718. doi: 10.1038/351714a0. [DOI] [PubMed] [Google Scholar]
  7. Bredt D. S., Snyder S. H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682–685. doi: 10.1073/pnas.87.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fulco A. J. P450BM-3 and other inducible bacterial P450 cytochromes: biochemistry and regulation. Annu Rev Pharmacol Toxicol. 1991;31:177–203. doi: 10.1146/annurev.pa.31.040191.001141. [DOI] [PubMed] [Google Scholar]
  9. Förstermann U., Schmidt H. H., Pollock J. S., Sheng H., Mitchell J. A., Warner T. D., Nakane M., Murad F. Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol. 1991 Oct 24;42(10):1849–1857. doi: 10.1016/0006-2952(91)90581-o. [DOI] [PubMed] [Google Scholar]
  10. Garthwaite J. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci. 1991 Feb;14(2):60–67. doi: 10.1016/0166-2236(91)90022-m. [DOI] [PubMed] [Google Scholar]
  11. Gerzer R., Böhme E., Hofmann F., Schultz G. Soluble guanylate cyclase purified from bovine lung contains heme and copper. FEBS Lett. 1981 Sep 14;132(1):71–74. doi: 10.1016/0014-5793(81)80429-2. [DOI] [PubMed] [Google Scholar]
  12. Haurand M., Ullrich V. Isolation and characterization of thromboxane synthase from human platelets as a cytochrome P-450 enzyme. J Biol Chem. 1985 Dec 5;260(28):15059–15067. [PubMed] [Google Scholar]
  13. Heinzel B., John M., Klatt P., Böhme E., Mayer B. Ca2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase. Biochem J. 1992 Feb 1;281(Pt 3):627–630. doi: 10.1042/bj2810627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Klatt P., Heinzel B., John M., Kastner M., Böhme E., Mayer B. Ca2+/calmodulin-dependent cytochrome c reductase activity of brain nitric oxide synthase. J Biol Chem. 1992 Jun 5;267(16):11374–11378. [PubMed] [Google Scholar]
  15. Kukovetz W. R., Holzmann S. Tolerance and cross-tolerance between SIN-1 and nitric oxide in bovine coronary arteries. J Cardiovasc Pharmacol. 1989;14 (Suppl 11):S40–S46. [PubMed] [Google Scholar]
  16. Mayer B., John M., Böhme E. Purification of a Ca2+/calmodulin-dependent nitric oxide synthase from porcine cerebellum. Cofactor-role of tetrahydrobiopterin. FEBS Lett. 1990 Dec 17;277(1-2):215–219. doi: 10.1016/0014-5793(90)80848-d. [DOI] [PubMed] [Google Scholar]
  17. Mayer B., John M., Heinzel B., Werner E. R., Wachter H., Schultz G., Böhme E. Brain nitric oxide synthase is a biopterin- and flavin-containing multi-functional oxido-reductase. FEBS Lett. 1991 Aug 19;288(1-2):187–191. doi: 10.1016/0014-5793(91)81031-3. [DOI] [PubMed] [Google Scholar]
  18. Mayer B., Schmidt K., Humbert P., Böhme E. Biosynthesis of endothelium-derived relaxing factor: a cytosolic enzyme in porcine aortic endothelial cells Ca2+-dependently converts L-arginine into an activator of soluble guanylyl cyclase. Biochem Biophys Res Commun. 1989 Oct 31;164(2):678–685. doi: 10.1016/0006-291x(89)91513-1. [DOI] [PubMed] [Google Scholar]
  19. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  20. Narhi L. O., Fulco A. J. Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium. J Biol Chem. 1986 Jun 5;261(16):7160–7169. [PubMed] [Google Scholar]
  21. OMURA T., SATO R. THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE. J Biol Chem. 1964 Jul;239:2370–2378. [PubMed] [Google Scholar]
  22. Ruettinger R. T., Wen L. P., Fulco A. J. Coding nucleotide, 5' regulatory, and deduced amino acid sequences of P-450BM-3, a single peptide cytochrome P-450:NADPH-P-450 reductase from Bacillus megaterium. J Biol Chem. 1989 Jul 5;264(19):10987–10995. [PubMed] [Google Scholar]
  23. Schmidt H. H., Pollock J. S., Nakane M., Gorsky L. D., Förstermann U., Murad F. Purification of a soluble isoform of guanylyl cyclase-activating-factor synthase. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):365–369. doi: 10.1073/pnas.88.2.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. White K. A., Marletta M. A. Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemistry. 1992 Jul 28;31(29):6627–6631. doi: 10.1021/bi00144a001. [DOI] [PubMed] [Google Scholar]

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