Title:The Disposal of Reactive Carbonyl Species through Carnosine Conjugation: What We Know Now
VOLUME: 27 ISSUE: 11
Author(s):Ettore Gilardoni, Giovanna Baron, Alessandra Altomare, Marina Carini, Giancarlo Aldini and Luca Regazzoni*
Affiliation:Department of Pharmaceutical Sciences, Universita degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Department of Pharmaceutical Sciences, Universita degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Department of Pharmaceutical Sciences, Universita degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Department of Pharmaceutical Sciences, Universita degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Department of Pharmaceutical Sciences, Universita degli Studi di Milano, Via Mangiagalli 25, 20133 Milan, Department of Pharmaceutical Sciences, Universita degli Studi di Milano, Via Mangiagalli 25, 20133 Milan
Keywords:Reactive carbonyl species, neurodegeneration, carnosine conjugates, trigger aberrant, glutathione, disease.
Abstract:
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.
