3.1Production of endogenous hydrogen sulfide
In mammalian cells, enzyme catalysis and non enzyme catalysis are two ways to produce endogenous hydrogen sulfide. Some studies have shown that enzyme catalysis is the main production route, and CBS, CSE and MST are the three key enzymes of this route[22-24].
Both CBS and CSE use pyridoxal phosphate (also known as vitamin B6) as cofactors, and their concentrations vary in different tissues[25, 26]. CBS mainly exists in the central nervous system (cerebellum, hippocampus) and liver tissue[27]. CSE mainly regulates H2S in cardiovascular system and respiratory system[28]. These two enzymes are only present in the cytoplasm and catalyze the conversion of homocysteine to cysteine, generating H2S, by participating in the reverse sulfur conversion pathway. Research has found that MST is also an enzyme involved in endogenous H2S production[29]. Unlike the two enzymes mentioned earlier, the cofactor of MST is zinc (Zn)[17]. It often co catalyzes with cysteine aminotransferase (CAT) in mitochondria to produce hydrogen sulfide, L-cysteine, and α-Ketoglutaric acid generates 3-mercaptopyruvic acid (3-MP) under the catalysis of CAT, and then generates hydrogen sulfide and pyruvic acid under the action of 3-MST[30]. In 2013, a new enzyme catalysis pathway was proposed by Japanese scientists[31]. This pathway occurs in peroxisome. D-amino acid oxidase (DAO) catalyzes D-cysteine to produce 3-MP, and then the product is transported to mitochondria through vesicles to participate in the next reaction[32-34]. Endogenous hydrogen sulfide enzymatic generation pathway (as shown in Figure 1). Some studies have found that when the human body is in the state of oxidative stress or hyperglycemia, the hydrogen sulfide produced through non enzyme catalysis will greatly increase. In red blood cells, the reduction equivalent produced by glucose oxidation can be utilized to reduce elemental sulfur or polysulfides to hydrogen sulfide[17].
Figure 1