Carnosine and protein carbonyl groups: a possible relationship.
Carnosine has been shown to react with low-molecular-weight aldehydes and ketones and has been proposed as a naturally occurring anti-glycating agent. It is suggested here that carnosine can also react with ("carnosinylate") proteins bearing carbonyl groups, and evidence supporting this idea is presented. Accumulation of protein carbonyl groups is associated with cellular ageing resulting from the effects of reactive oxygen species, reducing sugars, and other reactive aldehydes and ketones. Carnosine has been shown to delay senescence and promote formation of a more juvenile phenotype in cultured human fibroblasts. It is speculated that carnosine may intracellularly suppress the deleterious effects of protein carbonyls by reacting with them to form protein-carbonyl-carnosine adducts, i.e., "carnosinylated" proteins. Various fates of the carnosinylated proteins are discussed including formation of inert lipofuscin and proteolysis via proteosome and RAGE activities. It is proposed that the anti-ageing and rejuvenating effects of carnosine are more readily explainable by its ability to react with protein carbonyls than its well-documented antioxidant activity.
Hipkiss
A R
AR
Division of Biomolecular Sciences, GKT School of Biomedical Sciences, King's College London, London SE1 1UL, UK. alan.hipkiss@kcl.ac.uk.
D000447:Aldehydes / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D002336:Carnosine / Q000378:metabolism*; D006801:Humans; D007659:Ketones / Q000378:metabolism*; D011506:Proteins / Q000737:chemistry*; D011765:Pyruvaldehyde / Q000378:metabolism
D000447:Aldehydes; D000596:Amino Acids; D007659:Ketones; D011506:Proteins; D011765:Pyruvaldehyde; D002336:Carnosine