Figure 1. Schematic overview of the biosynthesis and disposal routes of hydrogen sulfide (H₂S).

(A) Transsulfuration pathway in cytoplasm generated by the PLP-dependent enzymes: CBS and CSE. Methionine and cysteine are the main substrates of CBS and CSE, with the production of some intermediates such as serine, NH₄, NH₃ and pyruvate. Diet is the sole source of methionine. (B) Alternative enzymatic generation of H₂S, mediated by GOT and MPST, mainly occurs in the mitochondrial matrix. (C) The oxidation pathway of H₂S facilitated by the suite of mitochondrial enzymes. The disposal starts with the generation of G-SSH by SQOR, followed by further action by either TST or ETHE1 combined with SUOX to produce thiosulfate and sulfate, which are eventually excreted. 3-MP, 3-mercaptopyruvate; CBS, cystathionine β synthase; CSE, cystathionine γ lyase; ETHE1, ethylmalonic encephalopathy 1; GOT, glutamate oxaloacetate transaminase; MPST, mercaptopyruvate sulfurtransferase; PLP, pyridoxal 5′-phosphate; SUOX, sulfite oxidase; III, IV, complex III & IV in respiratory chain; SQOR, sulfide quinone oxidoreductase; TST, thiosulfate sulfur transferase; Qox, Oxidised coenzyme Q; Qred, Reduced coenzyme Q. (Created with BioRender.com.)