3.2 Metabolism of endogenous hydrogen sulfide
In mammals, hydrogen sulfide is excreted differently in different systems. In the respiratory tract, hydrogen sulfide is directly excreted in the form of gaseous molecules; Through the urinary tract, H2S is mainly excreted in the form of thiosulfate or free sulfate in the urine. However, in the gastrointestinal tract, most hydrogen sulfide is still excreted in the form of free sulfide in the feces[17]. H2S mainly has the following three metabolic pathways:1). The elimination of hydrogen sulfide through the mitochondrial sulfide oxidation pathway, with sulfoquinone oxidoreductase (SQOR) being the key enzyme in this reaction. Firstly, hydrogen sulfide is oxidized to thiosulfate under the catalysis of SQOR[35, 36]. In this reaction, the main sulfur acceptor is glutathione (GSH), and the resulting product is glutathione disulfide (GSSH)[37, 38]. In the next step of the reaction, rhodanese (orTST) plays a crucial role as a sulfur transferase that can further oxidize thiosulfate to sulfite or sulfate[39, 40]. However, due to the rapid oxidation of sulfite to sulfate, hydrogen sulfide is ultimately expelled from the body in the form of thiosulfate or sulfate through this pathway[17, 40]. 2). Research has found that methylation occurring in the cytoplasm is another metabolic pathway for hydrogen sulfide[24]. Thiol-S-methyltransferase (TSMT) can catalyze the conversion of hydrogen sulfide to methyl mercaptan and dimethyl sulfide. TSMT is commonly present in cells in the human body, but has high activity in mucosal cells of the colon and cecum[41]. Compared to the sulfide oxidation pathway, the metabolic process of sulfide methylation is slower. In a study, the rate of sulfide methylation in mammalian colon mucosal cells was approximately 10000 times slower than the oxidation rate of H2S[42]. 3). Hydrogen sulfide can be cleared by methemoglobin, metal containing or sulfur containing macromolecules. Methemoglobin and myoglobin can promote the binding of hydrogen sulfide and iron by regulating the reactivity of iron, accelerating the oxidation rate of hydrogen sulfide[43].
Figure 2