ASTRACT: Several
amino acids were found to undergo progressive age-dependent racemisation in the lifelong
proteins of normal human
lenses. The two most highly racemised were Ser and Asx. By age 70, 4.5% of all Ser residues had been racemised, along with >9% of Asx residues. Such a high level of inversion, equivalent to between 2 and 3 D- amino
acids per
polypeptide chain, is likely to induce significant denaturation of the
crystallins in aged
lenses. Thr, Glx and Phe underwent age-dependent racemisation to a smaller degree. In model experiments, D- amino
acid content could be increased simply by exposing intact
lenses to elevated temperature. In
cataract lenses, the extent of racemisation of Ser, Asx and Thr residues was significantly greater than for age-matched normal
lenses. This was true, even for
cataract lenses removed from patients at the earliest ages where age-related
cataract is observed clinically. Racemisation of
amino acids in
crystallins may arise due to prolonged exposure of these
proteins to ocular temperatures and increased levels of racemisation may play a significant role in the opacification of human
lenses.