Protein carbonyl and the methionine sulfoxide reductase system.
The formation and accumulation of protein-carbonyl by reactive oxygen species may serve as a marker of oxidative stress, aging, and age-related diseases. Enzymatic reversal of the protein-carbonyl modification has not yet been detected. However, an enzymatic reversal of protein-methionine sulfoxide modification exists and is mediated by the methionine sulfoxide reductase (Msr) system. Methionine sulfoxide modifications to proteins may precede the formation of protein-carbonyl adducts because of consequent structural changes that increase the vulnerability of amino acid residues to carbonylation. Supportive evidence for this possibility arises from the elevated protein-carbonyl accumulations observed in organisms, such as yeast and mice, lacking the methionine sulfoxide reductase A (MsrA) enzyme. In addition, advanced age or enhanced oxidative-stress conditions foster the accumulations of protein-carbonyls. This review discusses the possible involvement of methionine sulfoxide formation in the occurrence of protein-carbonyl adducts and their relevance to the aging process and neurodegenerative diseases.
Moskovitz
Jackob
J
Department of Pharmacology and Toxicology, University of Kansas , Lawrence, KS, USA. moskovij@ku.edu
Oien
Derek B
DB
D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases; D051379:Mice; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D050050:Protein Carbonylation / Q000235:genetics / Q000502:physiology*
D008715:Methionine; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; C013111:methionine sulfoxide