Oxidation of glycated proteins: age-dependent accumulation of N epsilon-(carboxymethyl)lysine in lens proteins.
N epsilon-(Carboxymethyl)lysine (CML) has been identified as a product of oxidation of fructoselysine (FL) in glycated (nonenzymatically glycosylated) proteins in vitro and has also been detected in human tissues and urine [Ahmed et al. (1986) J. Biol. Chem. 261, 4889-4894]. In this study, we compare the amounts of CML and FL in normal human lens proteins, aged 0-79 years, using specific and sensitive assays based on selected ion monitoring gas chromatography-mass spectrometry. Our results indicate that the lens content of FL increases significantly between infancy and about age 5 but that there is only a slight, statistically insignificant increase in FL between age 5 and 80 (mean +/- SD = 1.4 +/- 0.4 mmol of FL/mol of Lys). In contrast, the lens content of the oxidation product, CML, increased linearly with age, ranging from trace levels at infancy up to 8 mmol of CML/mol of lysine at age 79. The ratio of CML to FL also increased linearly from 0.5 to 5 mol of CML/mol of FL between age 1 and 79, respectively. These results indicate that CML, rather than FL, is the major product of glycation detectable in adult human lens protein. The age-dependent accumulation of CML in lens protein indicates that products of both glycation and oxidation accumulate in the lens with age, while the constant rate of accumulation of CML in lens with age argues against an age-dependent decline in free radical defense mechanisms in this tissue.
Dunn
J A
JA
Department of Chemistry, School of Medicine, University of South Carolina, Columbia 29208.
Patrick
J S
JS
Thorpe
S R
SR
Baynes
J W
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D002852:Chromatography, Ion Exchange; D003459:Crystallins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction
D003459:Crystallins; C033186:fructosyl-lysine; C048496:N(6)-carboxymethyllysine; D008239:Lysine