The Importance of the Idea of “Parachirality” in Life Science

Abstract Homochirality is essential for the development and maintenance of life. Therefore biochemists have not paid much attention to the presence and function of biologically uncommon d -amino acids in living organisms. However, recent improvements in analytical techniques have facilitated the accurate analysis of amino acid enantiomers. Consequently, d -amino acids have been detected in a variety of living higher organisms in the form of free, peptide-bound and protein-bound amino acids. d -aspartyl (Asp) residues present as protein-bound d -amino acids have been widely detected in proteins obtained from various tissues of elderly individuals. The presence of d -Asp in aged tissues of living organisms is a result of the spontaneous racemization of Asp residues during aging. This racemization does not occur uniformly but does so at specific residues on the basis of sequence context or structural considerations that make these sites more susceptible to racemization than others. It is therefore informative to determine the nature of the Asp residues at racemization sites within particular proteins. To date, however, the detection of d -amino acids in proteins has been complex and difficult. In this review, we show the methods for the analysis of protein-bound d -amino acids based on LC-MS/MS that can identify the specific sites of d -Asp in proteins. Furthermore, we show where and how d -amino acids are generated in proteins of living tissues under physiological conditions, and describe the effects of d -amino acid formation on proteins using lens crystallins as an example. Elucidation of the mechanisms underlying the onset of age-related diseases such as cataract and Alzheimer’s disease may be achieved by consideration of the idea of “parachirality”, where d -amino acids are incorporated into the l -amino acid arena of life.