Formation of Four Isomers at the Asp-151 Residue of Aged Human αA-Crystallin by Natural Aging

Racemisation and human cataract. d-Ser, d-Asp/Asn and d-Thr are higher in the lifelong proteins of cataract lenses than in age-matched normal lenses

“…Our data agree well with those of Masters et al (1977) who found D-Asx to accumulate in proteins of normal lenses at a rate of 0.14% per year. The data are also in agreement with studies from Fujii's laboratory who elucidated sites on alpha crystallins (Fujii et al 1999b;Nakamura et al 2008) that are particularly susceptible to racemisation of Asp. Since the vast bulk of protein in the lens is made up of crystallins (Harding 1991), it was possible to convert this figure to an average number of residues per polypeptide chain, assuming that all crystallins were affected equally.…”

“…The reasons for this are not yet clear, but may suggest that some Ser, Thr and Asx residues are more susceptible to inversion than others. Asp 151 in alpha A crystallin, which has been identified by Fujii's group as being particularly susceptible to racemisation in human lenses (Fujii et al 1999b) may be one such site, since our initial data suggest that it is approximately 25% racemized by age 20. Conformationally, flexible regions, those in the terminal regions of proteins (Di Salvo et al 1999) and those that contain favourable sequences, such as Asx-Gly, may be particularly susceptible to inversion (Radkiewicz et al 2001).…”

Racemization of Two Proteins over Our Lifespan: Deamidation of Asparagine 76 in γS Crystallin Is Greater in Cataract than in Normal Lenses across the Age Range

“…An Asp residue in aA crystallin (Asp 151) was selected, as it was known from previous work to be subject to modification. 31,33 The rate of change in this Asp was compared with that of an Asn residue in cS crystallin (Asn 76), since this site was found to undergo significant deamidation with age, and importantly, to be more highly modified in cataract than in age-matched normal lenses. 13 Lenses across the age range were examined and the extent of modification at both sites was compared.…”

“…One, an Asp residue in aA crystallin (Asp 151), has been shown to be significantly racemised in old human lenses. 31 The other is an Asn residue in cS crystallin (Asn 76) and was chosen because it was found to be almost twice as deamidated in 60-to 70-year-old cataract lenses as in normal controls. 13 Particular attention was directed at deter-mining the time course of deamidation and of discovering the major products formed at each site.…”

Gas chromatographic quantification of free D‐amino acids in higher vertebrates

“…For the relevance of d-amino acids to nutritional and physiological aspects see the comprehensive review by Friedman (1999), for the analytical chemistry and biochemistry see the overview by Imai et al (1996), and for plant d-amino acids to a report by Brückner and Westhauser (2003). New areas of interest of d-amino acids are, for example, the genesis of d-amino acids and mode of action of the resulting antimicrobial peptides found in skin secretions of frogs belonging to the genus Bombina, or neuropeptides of molluscs belonging to species of genera such as Achatina, Helix or Conus (Jolles, 1998), the role of free and N-methylated d-amino acids in nervous and brain tissues (D'Aniello et al, 2000) or aspartate isomerization in human lens proteins (Fujii et al, 1999).…”