D-amino acid residues in proteins related to aging and age-related diseases and a new analysis of the isomers in proteins

Abstract

Homochirality is essential for the development and maintenance of life. Until relatively recently, the homochirality of amino acids in living systems was believed to be maintained with the exception of the presence of D-amino acids in the cell wall of microorganisms. However, D-amino acids were recently found in various higher organisms in proteins and peptides and as free amino acids. In proteins, D-aspartate (Asp) residues have been detected in various tissues such as the eye lens, teeth, bone, aorta, ligament, brain, and skin of elderly individuals, and thus D-amino acids can no longer be considered as uncommon in living organisms. The presence of D-amino acids may change the higher-order structure of proteins, and this may be the cause of age-related diseases including cataract and Alzheimer’s disease. D-Asp in aged tissues of living organisms is thought to result from the spontaneous racemization of the Asp residues. The racemization of Asp residues in proteins does not occur uniformly but does so at specific residues on the basis of the sequence context or structural considerations. Therefore, it is necessary to determine the nature of Asp residues at specific sites within particular proteins. However, the detection of D-amino acids in proteins to date has been complex and difficult. This review deals with 1) the presence of D-aspartate (Asp) residues in protein of living tissues, 2) the mechanism of D-Asp formation in protein under physiological conditions, 3) the influence of D-Asp on protein structure and function, and 4) recent advances in D-amino acid analysis in protein.