Formation of four isomers at the Asp-151 residue of aged human αA-crystallin by natural aging

Although proteins are generally composed entirely of L-amino acids, we have previously shown that Asp-151 in alpha A-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 beta-Asp (isoaspartate) residue simultaneously; therefore, four isomers of Asp-151, normal L-alpha-Asp and biologically uncommon L-beta-Asp, D-alpha-Asp, and D-beta-Asp, are formed in alpha A-crystallins. In the present study, we measured the ratio of the four isomers of Asp-151 in alpha A-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-alpha-Asp in the alpha A-crystallin of the human lenses of the 80-year-olds. These drastic changes started at birth, with about 45% of normal L-alpha-Asp lost by 30 years. These modifications of the Asp residue likely affect the three-dimensional packing array of the lens proteins. (C) 1999 Academic Press.