Carbonyl proteins

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Fragmentation of a polypeptide chain. The reaction taking place on the right side leads to a carbonyl protein.
A break in a polypeptide strand due to the oxidation of a glutamic acid residue also leads to a carbonyl protein.

Carbonyl proteins are oxidation products of proteins (proteins). They arise in the cells of organisms through the action of reactive oxygen and reactive nitrogen species on proteins, peptides and amino acids , whereby aldehydes and ketones - both compounds with a reactive carbonyl group - are formed. The carbonyl proteins formed by the protein oxidation serve as biomarkers for the determination of oxidative stress in laboratory medicine .

Emergence

Carbonyl proteins result from the oxidation of proteins, both in vivo (in the living organism) and in vitro , for example in a cell culture . The oxidation reaction is often metal catalyzed. The level of carbonyl proteins in a given tissue is a direct measure of the oxidative stress the tissue has been exposed to. As a result of the oxidation, the proteins are marked for catalytic degradation by peptidases in the cytosol . The oxidation of proteins is one of the causes of damaged enzymes, the number of which increases with age and in a number of pathological conditions. For example, carbonyl proteins play a key role in the development of cataracts . Via the reactive aldehyde or keto groups, imines can be formed from other proteins through reaction with terminal amino groups or the amino group in the side chain of lysine . The proteins are cross-linked . Cross-linked proteins are largely without function and can only be broken down by the cells inadequately. They are therefore encapsulated and deposited in the cells. One example is the age pigment lipofuscin . The cause of the oxidative stress, which leads to the formation of carbonyl proteins, are stress loads on the organism of all kinds. Illnesses, operations and injuries, ischemia and reperfusions play a role in this; especially inflammation . But sport, both anaerobic and aerobic exercise, increase the production of reactive oxygen and nitrogen species, the oxidation products of which - including carbonyl proteins - can be detected after appropriate exercise. At the same time, the endogenous antioxidant defense of the cells is activated through exercise. Even in normal healthy tissue, the proteins contain small amounts of carbonyl groups. The value is around 0.1 µmol per gram of protein, which corresponds to about one keto group for every 30,000 amino acids. Under the conditions of oxidative stress, these values ​​are increased by a factor of 2 to 20.

Diagnostics and analytics

The content of Carbonylproteinen, for example, by dot blot using an anti- 2,4-dinitrophenylhydrazine - antibody to be determined. The determination can be carried out spectroscopically directly with 2,4-dinitrophenylhydrazine even without the corresponding antibody. Other methods work with tritiated sodium borate , with which the carbonyl groups are selectively reduced.

further reading

  • R. Widmer: Effect of inhibitors and antioxidants in glial cells in anoxia / reoxygenation and in hepatic encephalopathy. Dissertation, TU Berlin, 2007
  • B. Chakravarti and DN Chakravarti: Oxidative modification of proteins: age-related changes. In: Gerontology 53, 2007, pp. 128-139. PMID 17164550 (Review)
  • RL Levine and ER Stadtman: Carbonylated proteins and their implication in pathology and physiology. In: Redox Proteomics: From Protein Modifications To Cellular Dysfunction And Diseases. I. Dalle-Donne, A. Scaloni and A. Butterfield (Editors), Wiley Interscience Series on Mass Spectrometry, 2006, ISBN 0-471-72345-2 , pp. 123-157.
  • R. Koo-Ng et al .: Carbonyl Levels in Type I and II Fiber-Rich Muscles and Their Response to Chronic Ethanol Feeding In Vivo and Hydroxyl and Superoxide Radicals In Vitro. In: Alcoholism: Clinical and Experimental Research 24, 2006, pp. 1862-1868. doi : 10.1111 / j.1530-0277.2000.tb01991.x
  • Z. Radak et al .: Super-marathon race increases serum and urinary nitrotyrosine and carbonyl levels. In: Eur J Clin Invest 33, 2003, pp. 726-730. PMID 12864784
  • RL Levine et al: Determination of carbonyl content in oxidatively modified proteins Methods Enzymol. 186, 1990, pp. 464-478. PMID 1978225

Web links

Individual evidence

  1. ^ ER Stadtman and RL Levine: Chemical modification of proteins by reactive oxygen species. In: Redox Proteomics: From Protein Modifications To Cellular Dysfunction And Diseases. I. Dalle-Donne, A. Scaloni and A. Butterfield (Editors), Wiley Interscience Series on Mass Spectrometry, 2006, ISBN 0-471-72345-2 , p. 4.
  2. ^ ER Stadtman and RL Levine: Chemical modification of proteins by reactive oxygen species. In: Redox Proteomics: From Protein Modifications To Cellular Dysfunction And Diseases. I. Dalle-Donne, A. Scaloni and A. Butterfield (Editors), Wiley Interscience Series on Mass Spectrometry, 2006, ISBN 0-471-72345-2 , p. 5.
  3. ↑ J. Greilberger et al.: Malondialdehyde, carbonyl proteins and albumin-disulphide as useful oxidative markers in mild cognitive impairment and Alzheimer's disease. In: Free Radic Res 42, 2008, pp. 633-638, PMID 18654878 .
  4. ↑ ER Stadtman: Protein oxidation and aging. In: Science 257, 1992, pp. 1220-1224. doi : 10.1126 / science.1355616
  5. ^ RL Levine: Carbonyl modified proteins in cellular regulation, aging, and disease. In: Free Radic Biol Med 32, 2002, pp. 790-796, PMID 11978480 .
  6. ^ A b F. Boscia et al .: Protein Oxidation and Lens Opacity in Humans. In: Investigative Ophthalmology and Visual Science 41, 2000, pp. 2461-2465, PMID 10937554 .
  7. ↑ C. Behl and B. Moosmann: Molecular Mechanisms of Aging - About the aging of cells and the influence of oxidative stress on the aging process. In: What is age (es)? UM Staudinger and H. Häfner (editors), Verlag Springer, 2008, doi : 10.1007 / 978-3-540-76711-4 ISBN 978-3-540-76710-7 , pp. 9-32.
  8. ↑ RJ Bloomer: Effect of exercise on oxidative stress biomarkers. In: Adv Clin Chem 46, 2008, pp. 1-50, PMID 19004186 .
  9. ↑ J. Greilberger: Dietary supplements and oxidative stress in popular sports and wellness. (PDF file; 348 kB), accessed on January 19, 2010.
  10. ↑ T. Ishii et al: A mutation in the SDHC gene of complex II increases oxidative stress, resulting in apoptosis and tumorigenesis. In: Cancer Res 65, 2005, pp. 203-209, PMID 15665296 .
  11. ↑ AG Lenz et al .: Determination of carbonyl groups in oxidatively modified proteins by reduction with tritiated sodium borohydride. In: Anal Biochem 177, 1989, pp. 419-425, PMID 2567130 .