Carbonyl Stress Chemistry

Exogenous and endogenous factors can induce an increase in oxidative stress, which causes a change in the cell's redox status and is accompanied by the formation of reactive oxygen species (ROS). ROS are triggers of several non-enzymatic processes, such as lipid peroxidation, glycation of protein molecules, and auto-oxidation of amino acids and monosaccharides. At the same time, some metabolic processes, for example, glycolysis and its switching to the polyol pathway, increased metabolism of ketone bodies, induce the formation of another kind of unstable substance – reactive carbonyl species (RCS), which can exhibit cytotoxic and mutagenic effects. Excessive formation and/or improper detoxification of RCS leads to the development of a specific form of oxidative stress, carbonyl stress, which is accompanied by irreversible structural and functional changes in biomolecules. As a result, abnormal products are formed – Advanced glycation and lipoxidation end products (AGEs/ALEs) and Advanced oxidation protein products. ROS, RCS, and AGEs/ALEs trigger signaling transduction pathways that alter cell metabolism and behavior. In addition, activation of receptors for AGEs (RAGE) provokes the formation of ROS. AGE- induced oxidative stress causes endoplasmic reticulum stress and triggers apoptosis of target cells. The intensity of these processes depends on the effectiveness of the antioxidant protection system, the functioning of the glyoxalase system, aldehyde dehydrogenases, carbonyl reductases (aldo-keto reductases), the presence of transition metal ions chelators, natural or synthetic ROS and RCS scavengers. The number of studies on carbonyl stress is growing rapidly, and a significant amount of information is accumulated on the mechanisms of stress reactions underlying pathological changes in various diseases. The purpose of this review is to summarize current data on the mechanisms of implementation of carbonyl stress reactions and neutralization of highly reactogenic carbonyl compounds.