Skip to main content
SpringerLink
Log in

Free Radical Mediated Oxidation of Proteins

  • Chapter
Free Radicals, Oxidative Stress, and Antioxidants

Part of the book series: NATO ASI Series ((NSSA,volume 296))

Abstract

Living organisms are constantly bombarded with a battery of oxygen free radicals and other forms of reactive oxygen, leading to the modification of proteins. These modifications include: (a) fragmentation of the polypeptide chain, (b) formation of intra- and inter-molecular cross-linkages, direct oxidation of amino acid residue side chains, (c) derivatization of amino groups of lysine by reducing sugars or their oxidation products (glycation), (d) derivatization of lysine, histidine, or cysteine residues by lipid oxidation products (malondialdehyde, 2,3 unsaturated aldehydes), and (e) nitration of tyrosine residues. The generation of carbonyl derivatives (aldehydes, ketones) by some of these reactions may serve as markers of oxidative protein damage in aging and disease. The nitration of tyrosine residues can seriously compromise major mechanisms of enzyme regulation and signal transduction. And the formation of protein-protein cross linkages can lead to the accumulation of protease resistant protein polymers and inhibitors of proteases that degrade the oxidized forms of oxidatively modified proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ames, B. N., Shigenaga, M. K., and Hagen, T. M., 1993, Oxidants, antioxidants, and the degenerative diseases of aging, Proc. Natl. Acad. Sci. USA 90, 7915–7922.

    Article  CAS  Google Scholar 

  • Amici, A., Levine, R. L., Tsai, L., and Stadtman, E. R., 1989, Conversion of amino acid residues in proteins and amino acid homopolymers to carbonyl derivatives by metal-catalyzed reactions, J. Biol. Chem. 264, 3341–3346.

    CAS  Google Scholar 

  • Armstrong, R. C. and Swallow, A. J., 1969, Pulse-and gamma-radiolysis of aqueous solutions of tryptophan, Radiat. Res. 41, 563–579.

    Article  Google Scholar 

  • Arnelle, D. R. and Stamler, J. S., 1995, NO’, NO’, and NO- donation by S-nitrosothiols: Implication for regulation of physiological functions by S-nitrosylation and acceleration of disulfide formation, Arch. Biochem. Biophys. 318, 279–285.

    Article  CAS  Google Scholar 

  • Baynes, J. W., 1996, Perspectives in diabetes. Role of oxidative stress in development of complications in diabetes, Diabetes 40, 405–411.

    Article  Google Scholar 

  • Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., and Freeman, S., 1990 ), Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide, Proc. Natl. Acad. Sci. USA 87, 1620–1624.

    Article  CAS  Google Scholar 

  • Beckman, J. S., Chen, J., Ischiropoulous, H., and Crow, J. P., 1994, Oxidative chemistry of peroxynitrite, Methods Enzymol. 233, 229–239.

    Article  CAS  Google Scholar 

  • Beckman, J. S., Ischiropoulos, H., Zhu, L., van der Woerd, M., Smith, C., Chen, J., Harrison, J., Martin, J.C., and Tsai, M., 1992, Kinetics of superoxide dismutase-and iron-catalyzed nitration of phenolics by peroxynitrite, Arch. Biochem. Biophys. 298, 438–445.

    Article  CAS  Google Scholar 

  • Berlett, B. S. and Stadtman, E. R., 1996, Carbon dioxide stimulates nitration of tyrosine residues and inhibits oxidation of methionine residues in Escherichia coli glutamine synthetase by peroxynitrite, FASEB J. 10, Abstract #585.

    Google Scholar 

  • Berlett, B. S., Friguet, B., Yim, M. B., Chock, P. B., and Stadtman, E. R., 1996, Peroxynitrite-mediated nitration of tyrosine residues of Escherichia coli glutamine synthetase mimic adenylylation: Relevance to signal transduction, Proc. Natl. Acad. Sci. USA 93, 1776–1780.

    Article  CAS  Google Scholar 

  • Berlett, B. S., Levine, R. L., and Stadtman, E. R., 1996a, A comparison of the effects of ozone on the modification of amino acid residues in glutamine synthetase and bovine serum albumin, J. Biol. Chem. 271, 4177–4182.

    Article  CAS  Google Scholar 

  • Borg, D. C. and Schaich, K. M., 1988, Iron and iron-derived radicals, In: Oxygen radicals and tissue injury ( Halliwell, B., ed.), pp. 20–26, Proceedings of an Upjohn Symposium, Federation of American Societies for Experimental Biology, Bethesda, MD.

    Google Scholar 

  • Brodie, E. and Reed, D. J., 1990, Cellular recovery of glyceraldehyde-3-phosphate dehydrogenase activity and thiol status after exposure to hydroperoxide, Arch. Biochem. Biophys. 277, 228–233.

    Article  Google Scholar 

  • Brot, N. and Weissbach, H., 1983, Biochemistry and physiological role of methionine sulfoxide reductase in proteins, Arch. Biochem. Biophys. 233, 271–288.

    Article  Google Scholar 

  • Burcham, P. C. and Kuhan, Y. T., 1996, Introduction of carbonyl groups into proteins of the lipid peroxidation prpduct, malondialdehyde, Biochem. Biophys. Res. Commun. 220, 996–1001.

    Article  CAS  Google Scholar 

  • Cerami, A., Vlassara, H., and Brownlee, M., 1987, Glucose and aging, Sci. Am. 256, 90–96.

    Article  CAS  Google Scholar 

  • Chao, C.-C., Ma, Y.-S., and Stadtman, E. R., 1997, Modification of protein surface hydrophobicity and methionine oxidation by oxidative stress, Proc. Natl. Acad. Sci. USA 94, 2969–2974.

    Article  CAS  Google Scholar 

  • Climent, I. and Levine, R. L., 1991, Oxidation of the active site of glutamine synthetase: Conversion of arginine344 to -glutamyl semialdehyde, Arch. Biochem. Biophys. 189, 371–375.

    Article  Google Scholar 

  • Denicola, A., Freeman, B. A., Trujillo, M., and Radi, R., 1996, Peroxynitrite reaction with carbon dioxide/bicar-bonate: Kinetics and influence on peroxynitrite-mediated oxidations, Arch. Biochem. Biophys. 333, 49–58.

    Article  CAS  Google Scholar 

  • Domigan, N. M., Charlton, T. S., Duncan, M. W., Winterbourne, C. C., and Kettle, A. J., 1995, Chlorination of tyrosyl residues in peptides by myeloperoxidase and human neutrophils, J. Biol. Chem. 270, 16542–16548.

    Article  CAS  Google Scholar 

  • Eiserich, J. P., Cross, C. E., Jones, D., and Halliwell, B., 1996, Formation of nitrating and chlorinating species by reaction of nitrite with hypochlorous acid, J. Biol. Chem. 271, 19199–19206.

    Article  CAS  Google Scholar 

  • Farber, J. M. and Levine, R. L., 1986, Sequence of a peptide susceptible to mixed-function oxidation: Probable cation binding site in glutamine synthetase, J. Biol. Chem. 261, 4574–4578.

    CAS  Google Scholar 

  • Fletcher, G. L. and Okada, S., 1961, Radiation-induced formation of dihydroxy phenylalanine from tyrosine and tyrosine-containing peptides in aqueous solution, Radiat. Res. 15, 349–351.

    Article  CAS  Google Scholar 

  • Friguet, B., Szweda, L., and Stadtman, E. R., 1994, Susceptibility of glucose-6-phosphate dehydrogenase modified by 4-hydroxy-2-nonenal and metal-catalyzed oxidation to proteolysis by the multicatalytic protease, Arch. Biochem. Biophys. 311, 168–173.

    Article  CAS  Google Scholar 

  • Garrison, W. M., 1987, Reaction mechanisms in the radiolysis of peptides, polypeptides, and proteins, Chem. Rev. 87, 381–398.

    Article  CAS  Google Scholar 

  • Garrison, W. M., Jayko, M. E., and Bennett, W., 1962, Radiation-induced oxidation of proteins in aqueous solution, Radiat. Res. 16, 487–502.

    Article  Google Scholar 

  • Gieseg, S. P., Simpson, J. A., Charlton, T. S., Duncan, M. W., and Dean, R. T., 1993, Protein-bound 3,4-dihydroxyphenylalanine is a major product formed during hydroxyl radical damage to proteins, Biochemistry 32, 4780–4786.

    Article  CAS  Google Scholar 

  • Giulivi, C. and Davies, K. J. A., 1993, Dityrosine and tyrosine oxidation products are endogenous markers for the selective proteolysis of oxidatively modified red blood cell hemoglobin by (the 19S) proteosome, J. Biol. Chem. 268, 8752–8759.

    CAS  Google Scholar 

  • Grimes, H. D., Perkins, K. K., and Boss, W. F., 1983, Ozone degrades into hydroxyl radical under physiological conditions: A spin trapping study, Plant Physiol. 72, 1016–1020.

    Article  CAS  Google Scholar 

  • Grune, T., Reinheckel, T., Joshi, M., and Davies, K. J. A., 1995, Proteolysis in cultured liver epithelial cells during oxidative stress, J. Biol. Chem. 270, 2344–2351.

    Article  CAS  Google Scholar 

  • Guptasarma, P., Balasubramanian, D., Matsugo, S., and Saito, I., 1992, Hydroxyl radical mediated damage to proteins, with special reference to the crystallins, Biochemistry 31, 4296–4302.

    Article  CAS  Google Scholar 

  • Halliwell, B. and Gutteridge, J. M. C., 1990, Role of free radicals and catalytic metal ions in human disease: an overview, Methods Enzymol. 186, 1–85.

    Article  CAS  Google Scholar 

  • Heinecke, J. W., Li, W., Daehnke III, H. L., and Goldstein, J. A., 1993, Dityrosine, a specific marker of oxidation, is synthesized by the myeloperoxidase-hydrogen peroxide system of human neutrophils and macrophages, J. Biol. Chem. 268, 4069–4077.

    CAS  Google Scholar 

  • Huggins, T. G., Wells-Knecht, M. C., Detorie, N. A., Baynes, J. W., and Thorpe, S. R., 1993, Formation of 0-tyrosine and dityrosine in proteins during radiolytic and metal-catalyzed oxidation, J. Biol. Chem. 268, 12341–12347.

    CAS  Google Scholar 

  • Hunter, T., 1995, Protein kinases and phosphatases: The Ying and Yang of protein phosphorylation and signaling, Cell 80, 225–236.

    Article  CAS  Google Scholar 

  • Katayama, Y., 1996, Nitric oxide: Mysterious messenger—Its chemistry, biology, and new reagents for research, Dojindo Newsletter 3, Dojindo Laboratories, Bethesda, MD, pp. 3–18.

    Google Scholar 

  • Kato, Y., Kawakishi, S., Aoki, T., Itakura, K., and Osawa, T., 1997, Oxidative modification of tryptophan exposed to peroxynitrite, Biochem. Biophys. Res. Commun. 234, 82–84.

    Article  CAS  Google Scholar 

  • Kaur, H. and Halliwell, B., 1994, Aromatic hydroxylation of phenylalanine as an assay for hydroxyl radicals, Anal. Biochem. 220, 11–15.

    Article  CAS  Google Scholar 

  • Knight, K. L. and Mudd, J. B., 1984, The reaction of ozone with glyceraldehyde-3-phosphate dehydrogenase, Arch. Biochem. Biphys. 229, 259–269.

    Article  CAS  Google Scholar 

  • Kong, S.-K., Yim, M. B., Stadtman, E. R., and Chock, P. B., 1996, Peroxynitrite disables the tyrosine phosphorylation regulatory mechanism: Lymphocyte-specific tyrosine kinase fails to phosphorylate nitrated cdc2(6–20)NH2 peptide, Proc. Natl. Acad. Sci. USA 93, 3377–3382.

    Article  CAS  Google Scholar 

  • Kristal, B. S. and Yu, B. P., 1992, An emerging hypothesis: Synergistic induction of aging by free radicals and Maillard reactions, J. Gerontol. 47, B104 - B107.

    Article  Google Scholar 

  • Kuroda, M., Sakiyama, F., and Narita, K., 1975, Oxidation of tryptophan in lysozyme by ozone in aqueous solution, J. Biol. Chem. 78, 641–651.

    CAS  Google Scholar 

  • Levine, R. L., Mosoni, L., Berlett, B. S., and Stadtman, E. R., 1996, Methionine residues as endogenous antioxidants in proteins, Proc. Natl. Acad. Sci. USA 93, 15036–15040.

    Article  CAS  Google Scholar 

  • Lymar, S. V. and Hurt, J. K., 1995, Rapid reaction between peroxynitrite ion and carbon dioxide: Implications for biological activity, J. Am. Chem. Soc. 117, 8867–8868.

    Article  CAS  Google Scholar 

  • Lymar, S. V. and Hurst, J. K., 1996, Carbon dioxide: Physiological catalyst for peroxynitrite-mediated cellular damage or cellular protectant? Chem. Res. Toxicol. 9, 845–850.

    Article  CAS  Google Scholar 

  • Lymar, S. V., Jiang, Q., and Hurst, J. K., 1996. Mechanisms of carbon dioxide-catalyzed oxidation of tyrosine by peroxynitrite, Biochemistry 35, 7855–7861.

    Article  CAS  Google Scholar 

  • Maskos, Z., Rush, J. D., and Koppenol, W. H., 1992, The hydroxylation of tryptophan, Arch. Biochem. Biophys. 296, 514–520.

    Article  CAS  Google Scholar 

  • Maskos, Z., Rush, J. D., and Koppenol, W. H., 1992, The hydroxylation of phenylalanine and tyrosine: A comparison with salicylate and tryptophan, Arch. Biochem. Biophys. 296, 521–529.

    Article  CAS  Google Scholar 

  • Mohr, S., Stamler, J. S., and Brune, B., 1994, Mechanism of covalent modification of glyceraldehyde-3-phosphate dehydrogenase at its active site thiol by nitric oxide, peroxynitrite, and related nitrosating agents, FEBS Lett. 348, 223–227.

    Article  CAS  Google Scholar 

  • Monnier, V., 1990, Nonenzymatic glycosylation, the Maillard reaction and the aging process, J. Gerontol. 45, B106 - B111.

    Article  Google Scholar 

  • Monnier, V., Gerhardinger, C., Marion, M. S., and Taneda, S., 1995, Novel approaches toward inhibition of the Maillard reaction in vivo: Search, isolation, and characterization of prokaryotic enzymes which degrade glycated substrates. In: Oxidative Stress and Aging ( Cutler, R. G., Packer, L., Bertram, J., and Mori, A., eds.), pp 141–149, Birkhauser Verlag, Basel, Switzerland.

    Chapter  Google Scholar 

  • Neuzil, J., Gebiki, J. M., and Stocker, R., 1993, Radical-induced chain oxidation of proteins and its inhibition by chain-breaking antioxidants, Biochem. J. 293, 601–606.

    CAS  Google Scholar 

  • Pryor, W. A., 1994, Mechanisms of radical formation from reactions of ozone with target molecules in the lung, Free Radical Biol. Med. 17, 451–465.

    Article  CAS  Google Scholar 

  • Pryor, W. A. and Squadrito, G., 1995, The chemistry of peroxynitrite: A product from the reaction of nitric oxide with superoxide, Am. J. Physiol., L699 - L722.

    Google Scholar 

  • Pryor, W. A. and Uppu, R. M., 1993, A kinetic model for the competitive reactions of ozone with amino acid residues in proteins in reverse micelles, J. Biol. Chem. 268, 3120–3126.

    CAS  Google Scholar 

  • Pryor, W. A., Jin, X., and Squadrito, G. L., 1994, One-and two-electron oxidations of methionine by peroxynitrite, Proc. Natl. Acad. Sci. USA 91, 11173–11177.

    Article  CAS  Google Scholar 

  • Rubbo, H., Denicola, A., and Radi, R., 1994, Peroxynitrite inactivates thiol-containing enzymes of Trypanosoma cruzi energetic metabolism and inhibits cell respiration, Arch. Biochem. Biophys. 308, 96–112.

    Article  CAS  Google Scholar 

  • Schuenstein, E. and Esterbauer, H., 1979, Formation and properties of reactive aldehydes, In: Submolecular Biology of Cancer, pp 225–244, CIBA Foundation Series 67, Excerpta Medica, Elsevier, Amsterdam.

    Google Scholar 

  • Schuessler, H. and Schilling, K., 1984, Oxygen effect in radiolysis of proteins, Part 2, Bovine serum albumin, Int. J. Radiat. Biol. 45, 267–281.

    Article  CAS  Google Scholar 

  • Simpson, J. A., Giesseg, S. P., and Dean, R. T., 1993, Free radical and enzymatic mechanisms for the generation of protein bound reducing moieties, Biochem. Biophys. Acta 1156, 190–196.

    Article  CAS  Google Scholar 

  • Solar, S., 1985, Reactions of OH with phenylalanine in neutral aqueous solutions, Radiat. Phys. Chem. 26, 103–108.

    CAS  Google Scholar 

  • Stadtman, E. R., 1990, Metal ion-catalyzed oxidation of proteins: Biochemical mechanism and biological consequences, Free Rad. Biol. Med. 9, 315–325.

    Article  CAS  Google Scholar 

  • Stadtman, E. R., 1992, Protein oxidation and aging, Science 257, 1220–1224.

    Article  CAS  Google Scholar 

  • Stadtman, E. R., Chock, P. B., and Rhee, S. G., 1981, Interconvertible enzyme cycles in cellular regulation, Curr. Top. Cell. Regul. 18, 79–83.

    CAS  Google Scholar 

  • Stadtman, E. R. and Oliver, C. N., 1991, Metal catalyzed oxidation of proteins: Physiological consequences, J. Biol. Chem. 266, 2005–2008.

    CAS  Google Scholar 

  • Stamler, J. S., 1994, Redox signaling: Nitrosylation and related target interactions of nitric oxide, Cell 78, 931–936.

    Article  CAS  Google Scholar 

  • Swallow, A. J., 1960, Effect of ionizing radiation on proteins. RCO groups, peptide bond cleavage, inactivation, -SH oxidation, In: Radiation Chemistry of Organic Compounds ( Swallow, A. J., ed.), pp 211–224, Pergamon Press, New York.

    Google Scholar 

  • Taborsky, G., 1973, Oxidative modification of proteins in the presence of ferrous iron and air. Effect of ionic constituents of the reaction medium on the nature of the oxidation products, Biochemistry 12, 1341–1348.

    Article  CAS  Google Scholar 

  • Takahashi, R. and Goto, S., 1990, Alteration of aminoacyl-tRNA synthetase with age: Heat labilization of the enzyme by oxidative damage, Arch. Biochem. Biophys. 277, 228–233.

    Article  CAS  Google Scholar 

  • Uchida, K. and Kawakishi, S., 1993, 2-oxohistidine as a novel biological marker for oxidatively modified proteins, FEBS Lett. 332, 208–210.

    Google Scholar 

  • Uchida, K. and Stadtman, E. R., 1993, Covalent modification of 4-hydroxynonenal to glyceraldehyde-3-phosphate, J. Biol. Chem. 268, 6388–6393.

    CAS  Google Scholar 

  • Uchida, K., Kato, Y., and Kawakishi, S., 1990, A novel mechanism for oxidative damage of prolyl peptides induced by hydroxyl radicals, Biochem. Biophys. Res. Commun. 169, 265–271.

    Article  CAS  Google Scholar 

  • Uppu, R. M., Squadrito, G. L., and Pryor, W. A., 1996, Acceleration of peroxynitrite oxidations by carbon dioxide, Arch. Biochem. Biophys. 327, 335–343.

    Article  CAS  Google Scholar 

  • van der Vliet, A., Eiserich, J. P., O’Neill, C. A., Halliwell, B., and Cross, C. E., 1995, Tyrosine modification by reactive nitrogen species. A closer look, Arch. Biochem. Biophys. 319, 341–349.

    Article  Google Scholar 

  • Verweij, H., Christianse, K., and van Steveninck, J., 1982, Ozone-induced formation of O,O’-dityrosine cross-links in proteins, Biochim. Biophys. Acta 701, 180–184.

    Article  CAS  Google Scholar 

  • Vogt, W., 1995, Oxidation of methionine residues in proteins: Tools, targets, and reversal, Free Rad. Biol. Med. 18, 93–105.

    Article  CAS  Google Scholar 

  • Waite, H., 1995, Precursors of quinone tanning: DOPA-containing compounds, Methods Enzymol. 258, 1–20.

    Article  CAS  Google Scholar 

  • Wells-Knecht, M. C., Huggins, T. G., Dyer, G., Thorpe, S. R., and Baynes, J. W., 1993, Oxidized amino acids in lens protein with age, J. Biol. Chem. 268, 12348–12352.

    CAS  Google Scholar 

  • Winchester, R. V. and Lynn, K. R., 1970 ), X- and -radiolysis of some tryptophan dipeptides, Int. J. Radiat. Biol. 17, 541–549.

    Article  CAS  Google Scholar 

  • Winterbourne, C. C., 1985, Comparative reactivities of various biological compounds with myeloperoxidasehydrogen peroxide-chloride, and similarity of the oxidant to hypochloride, Biochim. Biophys. Acta 840, 204–210.

    Article  Google Scholar 

  • Zhou, J. Q. and Gafni, A., 1991, Exposure of rat muscle phosphoglycerate kinase to a nonenzymatic MFO system generates the old form of enzyme, J. Gerontol. 46, B217 - B221.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Biochemistry National Heart, Lung, and Blood Institute, National Institutes of Health, Building 3, Room 222, Bethesda, Maryland, 20892, USA

    Earl R. Stadtman

Authors
  1. Earl R. Stadtman
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Akdeniz University, Antalya, Turkey

    Tomris Özben

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer Science+Business Media New York

About this chapter

Cite this chapter

Stadtman, E.R. (1998). Free Radical Mediated Oxidation of Proteins. In: Özben, T. (eds) Free Radicals, Oxidative Stress, and Antioxidants. NATO ASI Series, vol 296. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2907-8_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-2907-8_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3292-1

  • Online ISBN: 978-1-4757-2907-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation