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

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Although proteins are generally composed entirely of l-amino acids, we have previously shown that Asp-151 in αA-crystallin from aged human lens is converted to the biologically uncommon d-isomer to a high degree. The formation of d-isomer was not simple racemization, but stereoinvertion. The reaction was also accompanied with isomerization to form β-Asp (isoaspartate) residue simultaneously; therefore, four isomers of Asp-151, normal l-α-Asp and biologically uncommon l-β-Asp, d-α-Asp, and d-β-Asp, are formed in αA-crystallins. In the present study, we measured the ratio of the four isomers of Asp-151 in αA-crystallins obtained from total lens proteins of human lenses of newborn and 30-, 60-, and 80-year-olds. The isomers increased with age, and the total amount of three isomers was more than that of normal l-α-Asp in the αA-crystallin of the human lenses of the 80-year-olds. These drastic changes started at birth, with about 45% of normal l-α-Asp lost by 30 years. These modifications of the Asp residue likely affect the three-dimensional packing array of the lens proteins.