Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein carbonyl groups

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. 2001 Elsevier Science Ireland Ltd. All rights reserved.