Fig. 3: Metabolic pathways involved in cysteine catabolism.
From: Cysteine metabolic circuitries: druggable targets in cancer
Cysteine can be a substrate for hydrogen sulphide (H2S) synthesis, be oxidatively catabolised to taurine or be a substrate for glutathione production. a The trans-sulphuration pathway. The enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) catalyse the conversion of homocysteine into cysteine, generate hydrogen sulphide through several alternative reactions or cysteine per/polysulphide (CysSS(n)H) with cystine as substrate. Cysteine is converted by cysteine aminotransferase (CAT) into 3-mercaptopyruvate (3-MP), which is a substrate of 3-MP sulphurtransferase (3-MST), of which there is a cytosolic and a mitochondrial isoform. 3-MST can also generate CysS(n)SH and glutathione per-/polysulphide (GS(n)SH), respectively, using Cys and GSH as sulphur acceptors. H2S is catabolised by a mitochondrial sulphide oxidation pathway. H2S is a substrate of sulphide:quinone oxidoreductase (SQR), which preferentially uses glutathione as a sulphur acceptor, to generate oxidised glutathione (GSSH) that is converted back into GSH by persulphide dioxygenase (PDO) using oxygen as co-substrate, yielding sulphite (SO32−) as co-product. Oxidised glutathione is also a substrate of rhodanese (Rhod), which uses SO32− as co-substrate to yield thiosulphate (S2O32−) and glutathione. SO32− oxidation by sulphite oxidase yields sulphate (SO42−). b Cysteine oxidation. Cysteine can be oxidised by cysteine dioxygenase (CDO) to cysteinesulphinate (CSA), which is converted by cysteinesulphinate decarboxylase (CSD) into hypotaurine (hT), which is further oxidised to taurine. Alternatively, cysteinesulphinate can be transaminated by aspartate aminotransferase (AAT) to 3-sulphinopyruvate (3-SP), which decomposes to form pyruvate and sulphite/sulphate. c Cysteine is a substrate for glutathione generation. Cysteine is converted into γ-glutamyl-cysteine (Glu-Cys) by glutamate-cysteine ligase (GCL) and subsequently to glutathione by glutathione synthase (GS). Conversely, GSH is converted into cysteinylglycine (Cys-Gly) by γ-glutamyl transpeptidase (γGT) and finally back to cysteine by dipeptidase (dPP).
