May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Allysine and 2-Aminoadipic Acid Are Markers of Protein Carbonyl Oxidation in Aging Human Lens
Author Affiliations & Notes
  • X. Fan
    Case Western Reserve Univ, Cleveland, Ohio
  • M. Theves
    Food Industry and Health, Institut Polytechnique LaSalle Beauvais, BEAUVAIS, France
  • C. M. Strauch
    Case Western Reserve Univ, Cleveland, Ohio
  • V. M. Monnier
    Case Western Reserve Univ, Cleveland, Ohio
    Pathology and Biochemistry,
  • Footnotes
    Commercial Relationships  X. Fan, None; M. Theves, None; C.M. Strauch, None; V.M. Monnier, None.
  • Footnotes
    Support  NEI EY07099
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3254. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      X. Fan, M. Theves, C. M. Strauch, V. M. Monnier; Allysine and 2-Aminoadipic Acid Are Markers of Protein Carbonyl Oxidation in Aging Human Lens. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3254. doi:

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : The aging human lens is susceptible to accumulation of damage to its proteins including phosphorylation, deamination, truncation, glycation, oxidation, and kynurenine adduct formation. These modifications have been associated with enhanced risk of crystalline aggregation. Now, we hypothesized that ε-amino group of lysine residues undergoes oxidative deamination with age to form the protein carbonyl allysine (α-aminoadipic acid-Δ-semialdehyde), which can further oxidize into 2-aminoadipic acid (2-AAA). (Biochem. J. 2007, 404:269-277). Accordingly, we determined both products in soluble and insoluble human lens protein from different ages.

Methods: : 55 human lenses (age range 6-79 years), comprising 33 and 22 non-diabetic and diabetic, respectively, were separated into soluble and insoluble fractions and reduced by sodium borohydride to convert allysine into 6-hydroxynorleucine (6OHLNL). The products were measured in acid hydrolysates by selective ion monitoring gas chromatography (GC-MS). Regression analysis, Spearman’s correlations and the Mann-Whitney Test were used for data analysis.

Results: : 6OHLNL increased 5 and 6-fold with age (p<0.0001) in both soluble and insoluble fraction. 2-aminoadipic acid also increased but less than 6OHLNL in soluble (p<0.01) and insoluble (p<0.05) fractions. Diabetes further increased 6OHLNL in both soluble (p<0.001) and insoluble fractions (p<0.0001).

Conclusions: : This discovery that oxidative deamination is ongoing process in the aging and diabetic human lens is novel and implies presence of catalytic metals. However, the exact mechanism of oxidation, i.e. oxoaldehyde-assisted (Suyama pathway) vs. myeloperoxidase, amine oxidase, or purely metal catalyzed remains to be determined. Interestingly, the fact that further oxidation of allysine to 2-AAA was modest in lens compared to skin suggests that the lens maintains a strong reducing environment. 6-OHLNL is a novel and distinct marker of protein oxidation compared carboxymethyl- (CML) and carboxyethyl-lysine (CEL).

Keywords: aging • oxidation/oxidative or free radical damage • cataract 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.