Racemization of aspartic acid in human proteins.
Aspartic acid racemization (AAR) represents one of the major types of non-enzymatic covalent modification that leads to an age-dependent accumulation of abnormal protein in numerous human tissues. In vivo racemization is an autonomic process during the "natural" ageing of proteins, and correlates with the age of long-lived proteins. Consequently AAR can be used as molecular indicator of protein ageing as well as for the identification of permanent proteins that age with the human organism. Although long-living, structural proteins are mainly affected, AAR may be significant on a time scale also relevant to enzymes and signaling proteins. It may result in a loss of protein function due to proteolysis or due to changes in the molecular structure. In vivo racemization may also increase in pathological conditions. AAR has already been discussed as a relevant pathophysiological factor in the pathogenesis of diseases of old age such as atherosclerosis, lung emphysema, presbyopia, cataract, degenerative diseases of cartilage and cerebral age-related dysfunctions. Although the details of the biological consequences of AAR have to be further elucidated, it is evident that AAR plays a role in the molecular biology of ageing.
Ritz-Timme
Stefanie
S
Institut für Rechtsmedizin der Christian-Albrechts-Universität zu Kiel, Arnold-Heller-Strasse 12, D-24105 Kiel, Germany.
Collins
Matthew J
MJ
D000375:Aging / Q000378:metabolism; D000577:Amides / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D013237:Stereoisomerism
D000577:Amides; D011506:Proteins; D001224:Aspartic Acid