CoChat
Sign Up
Cited by 415Redox biology and oxidative stressAntioxidant Activity and Oxidative StressAdvanced Glycation End Products research

Glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins

Open access
Requena, Jesús R., Chao, Chien-Chung, Levine, Rodney L., Stadtman, Earl R.·2001·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.98.1.69PMC PMC14546
Open this paper in CoChat — free account

Abstract

Metal-catalyzed oxidation results in loss of function and structural alteration of proteins. The oxidative process affects a variety of side amino acid groups, some of which are converted to carbonyl compounds. Spectrophotometric measurement of these moieties, after their reaction with 2,4-dinitrophenylhydrazine, is a simple, accurate technique that has been widely used to reveal increased levels of protein carbonyls in aging and disease. We have initiated studies aimed at elucidating the chemical nature of protein carbonyls. Methods based on gas chromatography/mass spectrometry with isotopic dilution were developed for the quantitation of glutamic and aminoadipic semialdehydes after their reduction to hydroxyaminovaleric and hydroxyaminocaproic acids. Analysis of model proteins oxidized in vitro by Cu 2+ /ascorbate revealed that these two compounds constitute the majority of protein carbonyls generated. Glutamic and aminoadipic semialdehydes were also detected in rat liver proteins, where they constitute ≈60% of the total protein carbonyl value. Aminoadipic semialdehyde was also measured in protein extracts from HeLa cells, and its level increased as a consequence of oxidative stress to cell cultures. These results indicate that glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins, and that this reaction is a major route leading to the generation of protein carbonyls in biological samples.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.98.1.69

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 26

  1. [1]Stadtman E R, Berlett B S. Drug Metab Rev. 1998;30:225–243. doi: 10.3109/03602539808996310. [DOI] [PubMed] [Google Scholar] · DOI
  2. [2]Berlett B S, Stadtman E R. J Biol Chem. 1997;272:20313–20316. doi: 10.1074/jbc.272.33.20313. [DOI] [PubMed] [Google Scholar] · DOI
  3. [3]Rivett A J, Levine R L. Arch Biochem Biophys. 1990;278:26–34. doi: 10.1016/0003-9861(90)90226-o. [DOI] [PubMed] [Google Scholar] · DOI
  4. [4]Fucci L, Oliver C N, Coon M J, Stadtman E R. Proc Natl Acad Sci USA. 1983;80:1521–1525. doi: 10.1073/pnas.80.6.1521. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  5. [5]Levine R L, Williams J A, Stadtman E R, Shacter E. Methods Enzymol. 1994;233:346–357. doi: 10.1016/s0076-6879(94)33040-9. [DOI] [PubMed] [Google Scholar] · DOI
  6. [6]Oliver C N, Ahn B-w, Moerman E J, Goldstein S, Stadtman E R. J Biol Chem. 1987;262:5488–5491. [PubMed] [Google Scholar]
  7. [7]Starke-Reed P E, Oliver C N. Arch Biochem Biophys. 1989;275:559–567. doi: 10.1016/0003-9861(89)90402-5. [DOI] [PubMed] [Google Scholar] · DOI
  8. [8]Sohal R S, Agarwal S, Dubey A, Orr W C. Proc Natl Acad Sci USA. 1993;90:7255–7259. doi: 10.1073/pnas.90.15.7255. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  9. [9]Smith C D, Carney J M, Starke-Reed P E, Oliver C N, Stadtman E R, Floyd R A, Markesbery W R. Proc Natl Acad Sci USA. 1991;88:10540–10543. doi: 10.1073/pnas.88.23.10540. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  10. [10]Garland D, Russell P, Zigler J S. In: Oxygen Radicals in Biology and Medicine. Simic M G, Taylor K S, Ward J F, von Sontag V, editors. New York: Plenum; 1994. pp. 347–353. [Google Scholar]
  11. [11]Bowling A C, Schultz J B, Brown R H, Jr, Beal M F. J Neurochem. 1993;61:2322–2325. doi: 10.1111/j.1471-4159.1993.tb07478.x. [DOI] [PubMed] [Google Scholar] · DOI
  12. [12]Gladstone I M, Levine R L. Pediatrics. 1994;93:764–768. [PubMed] [Google Scholar]
  13. [13]Cao G, Cutler R G. Arch Biochem Biophys. 1995;320:106–114. doi: 10.1006/abbi.1995.1347. [DOI] [PubMed] [Google Scholar] · DOI
  14. [14]Amici A, Levine R L, Tsai L, Stadtman E R. J Biol Chem. 1988;264:3341–3346. [PubMed] [Google Scholar]
  15. [15]Swallow D L, Abraham E P. Biochem J. 1959;72:326–332. doi: 10.1042/bj0720326. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  16. [16]Gaudry R. Can J Res. 1948;326:387–392. doi: 10.1139/cjr48b-037. [DOI] [PubMed] [Google Scholar] · DOI
  17. [17]Baldwin J E, Killin S J, Adlington R M, Spiegel U. Tetrahedron. 1988;44:2633–2636. [Google Scholar]
  18. [18]Hofmann K, Stutz E, Spuhler G, Yajima H, Schwartz E T. J Am Chem Soc. 1960;82:3727–3732. [Google Scholar]
  19. [19]Rivett A J. J Biol Chem. 1985;260:300–305. [PubMed] [Google Scholar]
  20. [20]Knecht K J, Dunn J A, McFarland K F, McCance D R, Lyons T J, Thorpe S R, Baynes J W. Diabetes. 1991;40:190–196. doi: 10.2337/diab.40.2.190. [DOI] [PubMed] [Google Scholar] · DOI
  21. [21]Ahmed M U, Brinkmann-Frye E, Degenhardt T P, Thorpe S R, Baynes J W. Biochem J. 1997;324:565–570. doi: 10.1042/bj3240565. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  22. [22]Tredget E E, Falk N, Scott P G, Hogg A M, Burke J F. Anal Biochem. 1990;190:259–265. doi: 10.1016/0003-2697(90)90190-k. [DOI] [PubMed] [Google Scholar] · DOI
  23. [23]Requena J R, Stadtman E R. Biochem Biophys Res Commun. 1999;264:207–211. doi: 10.1006/bbrc.1999.1502. [DOI] [PubMed] [Google Scholar] · DOI
  24. [24]Ayala A, Cutler R G. Free Radical Biol Med. 1996;21:65–80. doi: 10.1016/0891-5849(95)02220-1. [DOI] [PubMed] [Google Scholar] · DOI
  25. [25]Pietzsch J. Biochem Biophys Res Commun. 2000;270:852–857. doi: 10.1006/bbrc.2000.2533. [DOI] [PubMed] [Google Scholar] · DOI
  26. [26]Ayala A, Cutler R G. Free Radical Biol Med. 1996;21:551–558. doi: 10.1016/0891-5849(96)00125-6. [DOI] [PubMed] [Google Scholar] · DOI

Cited by

Sorted by citations

Authors
Requena, J. R., Chao, C.-C., Levine, R. L., & Stadtman, E. R.
Affiliations
National Institutes of Health (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2000-12-19
Volume
98
Issue
1
Pages
69-74
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.98.1.69
PMC
PMC14546
OpenAlex
W2139344973
Cited by
415
References
0
Citations by year
2026: 4 · 2025: 15 · 2024: 4 · 2023: 15 · 2022: 14 · 2021: 16 · 2020: 7 · 2019: 22 · 2018: 10 · 2017: 19 · 2016: 18 · 2015: 12 · 2014: 15 · 2013: 24 · 2012: 24
FWCI
2.77
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • SUNY Digital Repository Support (State University of New York System) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Keywords
protein carbonylation, oxidative stress, HeLa cells, 2,4-dinitrophenylhydrazine derivatization
MeSH terms
Aldehydes, Animals, Cells, Cultured, Chromatography, High Pressure Liquid, Copper, Glucose, Glucose Oxidase, HeLa Cells, Humans, Liver, Gas Chromatography-Mass Spectrometry, Metals, Oxidation-Reduction, Phenylhydrazines, Proteins, Rats, Inbred F344, 2-Aminoadipic Acid, Oxidative Stress, Glutamic Acid, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review