Reactive Carbonyl Species are electrophiles generated by the oxidative cleavage of
lipids and
sugars. Such compounds have been described as important molecules for cellular signaling, whilst their accumulation has been found to be cytotoxic as they may trigger aberrant modifications of
proteins (a process often referred to as carbonylation). A correlation between carbonylation of
proteins and human
disease progression has been shown in ageing, diabetes,
obesity,
chronic renal failure, neurodegeneration and
cardiovascular disease. However, the fate of reactive carbonyl species is still far from being understood, especially concerning the mechanisms responsible for their disposal as well as the importance of this in
disease progression. In this context, some data have been published on phase I and phase II deactivation of reactive carbonyl species. In the case of phase II mechanisms, the route involving
glutathione conjugation and subsequent disposal of the adducts has been extensively studied both in vitro and in vivo for some of the more representative compounds, e.g.
4-hydroxynonenal. There is also emerging evidence of an involvement of
carnosine as an endogenous alternative to
glutathione for phase II conjugation. However, the fate of
carnosine conjugates is still poorly investigated and, unlike
glutathione, there is little evidence of the formation of
carnosine adducts in vivo. The acquisition of such data could be of importance for the development of new drugs, since
carnosine and its derivatives have been proposed as potential therapeutic agents for the mitigation of carbonylation associated with
disease progression. Herein, we wish to review our current knowledge of the binding of reactive carbonyl species with
carnosine together with the disposal of
carnosine conjugates, emphasizing those aspects still requiring investigation such as conjugation reversibility and
enzyme assisted catalysis of the reactions.