Abstract
Accumulating evidence shows that H2S has physiological functions in various tissues and organs. It includes regulation of neuronal activity, vascular tension, a release of insulin, and protection of the heart, kidney, and brain from ischemic insult. H2S is produced by enzymes from l-cysteine; cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase. We recently discovered an additional pathway for the production of H2S from d-cysteine. d-Amino acid oxidase provides 3-mercaptopyruvate for 3MST to produce H2S. d-Cysteine protects cerebellar neurons from oxidative stress and attenuates ischemia-reperfusion injury caused in the kidney more effectively than l-cysteine. This review focuses on a novel pathway for the production of H2S and its therapeutic application especially to the renal diseases.
Highlights
The discovery of endogenous sulfide in the brain urged us to study the function of hydrogen sulfide (H2S) in the brain [1,2,3]
H2S is produced from l-cysteine by two pyridoxal 5 phosphate (PLP)-dependent enzymes, cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) and pyridoxal phosphate (PLP)-independent 3-mercaptopyruvate sulfurtransferase (3MST) (Figure 1) [7, 9, 20,21,22,23]. 3MST produces H2S from 3-mercaptopyruvate (3MP), an achiral α-keto acid, which is generated by PLP-dependent cysteine aminotransferase (CAT) from l-cysteine and α-ketoglutarate [24,25,26]
We recently discovered a novel pathway with d-cysteine as a substrate [27]
Summary
Accumulating evidence shows that H2S has physiological functions in various tissues and organs. It includes regulation of neuronal activity, vascular tension, a release of insulin, and protection of the heart, kidney, and brain from ischemic insult. H2S is produced by enzymes from L-cysteine; cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase. We recently discovered an additional pathway for the production of H2S from D-cysteine. D-Amino acid oxidase provides 3-mercaptopyruvate for 3MST to produce H2S. D-Cysteine protects cerebellar neurons from oxidative stress and attenuates ischemia-reperfusion injury caused in the kidney more effectively than L-cysteine. This review focuses on a novel pathway for the production of H2S and its therapeutic application especially to the renal diseases
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