title: Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein carbonyl groups.
abstract: Carnosine (beta-alanyl-L-histidine) is a physiological dipeptide which can delay ageing and rejuvenate senescent cultured human fibroblasts. Carnosine's anti-oxidant, free radical- and metal ion-scavenging activities cannot adequately explain these effects. Previous studies showed that carnosine reacts with small carbonyl compounds (aldehydes and ketones) and protects macromolecules against their cross-linking actions. Ageing is associated with accumulation of carbonyl groups on proteins. We consider here whether carnosine reacts with protein carbonyl groups. Our evidence indicates that carnosine can react non-enzymically with protein carbonyl groups, a process termed 'carnosinylation'. We propose that similar reactions could occur in cultured fibroblasts and in vivo. A preliminary experiment suggesting that carnosine is effective in vivo is presented; it suppressed diabetes-associated increase in blood pressure in fructose-fed rats, an observation consistent with carnosine's anti-glycating actions. We speculate that: (i) carnosine's apparent anti-ageing actions result, partly, from its ability to react with carbonyl groups on glycated/oxidised proteins and other molecules; (ii) this reaction, termed 'carnosinylation,' inhibits cross-linking of glycoxidised proteins to normal macromolecules; and (iii) carnosinylation could affect the fate of glycoxidised polypeptides.
authors.affiliation: Division of Biomolecular Sciences, GKT School of Biomedical Sciences, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK. alan.hipkiss@kcl.ac.uk
authors.forename: A R
authors.initials: AR
authors.lastname: Hipkiss
authors.forename: C
authors.initials: C
authors.lastname: Brownson
authors.forename: M J
authors.initials: MJ
authors.lastname: Carrier
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002336:Carnosine / Q000378:metabolism*; D008297:Male; D010047:Ovalbumin; D011765:Pyruvaldehyde; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D011765:Pyruvaldehyde; D002336:Carnosine; D010047:Ovalbumin