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Therefore, this review focuses on the cardioprotective and hepatoprotective role of H2S. In addition, the review provides a summary of several known molecular targets of H2S protection. For several centuries, hydrogen sulfide (H2S) had been known to be highly toxic. However, more recently H2S has been recognized as mediating a wide range of physiological effects. Through its presence and enzymatic production, H2S has gained attention for its signalling capabilities. In addition, the role that H2S plays in attenuating ischaemia�Creperfusion injury has begun to be elucidated. This review focuses on the cytoprotective roles of H2S in the heart and the liver in the setting of ischaemia�Creperfusion injury and the mechanisms GPX4 of cytoprotection. buy Alectinib Hydrogen sulfide is synthesized in mammalian tissues via non-enzymatic pathways and endogenous enzymes (Singh & Banerjee, 2011). The enzymes responsible for the biosynthesis of H2S have been recently identified and await full characterization. There are multiple pathways that are known to produce H2S from l-cysteine. Cystathionine ��-synthase (CBS), a cytosolic enzyme, is the first and the rate-limiting step in the trans-sulfuration pathway (Beard & Bearden, 2011). Trans-sulfuration is the endogenous pathway for coupling toxic homocysteine removal with production of H2S. Cystathionine ��-synthase is the only enzyme available for terminal removal of homocysteine (Beard & Bearden, 2011). Specifically, CBS acts on l-cysteine to produce H2S and l-serine (Beard & Bearden, 2011; Singh & Banerjee, 2011). Another pyridoxal 5��-phosphate (PLP)-dependent cytosolic enzyme is cystathionine ��-lyase (CSE). Cystathionine ��-lyase forms thiocysteine from cystine, which rearranges to form H2S (Beard & Bearden, 2011; Li et al. 2011; Singh & Banerjee, 2011). Cysteine aminotranserase (CAT) catalyses the reaction of l-cysteine with keto acids to form 3-mercaptopyruvate, which is then desulfurated by the mitochondrial enzyme 3-mercaptopyuvate sulfurtransferase (3-MST; Li Osimertinib manufacturer et al. 2011). Cysteine desulfhydration is referred to as the primary mechanism for the production of H2S (Li et al. 2011; Singh & Banerjee, 2011). Once formed, H2S is broken down rapidly by a combination of chemical and enzymatic reactions. For example, H2S can react with methaemoglobin to form sulfhaemoglobin, which may act as a metabolic sink for H2S. In addition, H2S can undergo methylation by thiol-S-methyltransferase to yield methanethiol and dimethylsufide. Moreover, H2S can be rapidly oxidized to thiosulfate by mitochondria and subsequently converted to sulfite and sulfate (Li et al. 2011). Low micromolar or nanomolar (i.e. physiological) levels of H2S are known to promote vasodilatation, to upregulate antioxidant enzymes, to modulate mitochondrial respiration, to attenuate leukocyte-mediated inflammation and to inhibit apoptosis.