Resumo

GENOUD, Valeria  e  QUINTANA, Irene. N-homocysteinylation reactions related to hyperhomocysteinemia. Acta bioquím. clín. latinoam. [online]. 2016, vol.50, n.4, pp.679-685. ISSN 0325-2957.

Increased plasma homocysteine levels (hyperhomocysteinemia) are associated with occlusive vascular diseases, such as atherosclerosis and thrombosis. Reduced homocysteine (Hcy) and its cyclic ester, homocysteine thiolactone (HTL) would be involved in the detrimental effects associated to hyperhomocysteinemia. These two species, Hcy and HTL can spontaneously react with proteins, through S and N-homocysteinylation process, respectively. Both reactions produce post-translational protein changes, impairing structural and functional features. In recent years, interest has been developed in HTL and its effects on human health. N-homocysteinylation is the reaction between the carboxyl group of HTL and ε-amino group of lysine residues, rendering free sulfhydryl groups able to participate in redox reactions. N-homocysteinylated proteins are prone to misfolding and oxidative damage, inducing cytotoxic and immunogenic effects. Metabolic conversion of Hcy to HTL as well as protein N-homocysteinylation is one of the mechanisms underlying the development of pathologies associated to hyperhomocysteinemia, such as cardiovascular and neurodegenerative diseases.

Palavras-chave : Hyperhomocysteinemia; Homocysteine-thiolactone; N-homocysteinylation; Occlusive vascular disease.

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