Figure 2. Cysteine biosynthesis and import.
(A) The reverse transsulfuration pathway. Methionine, derived from the diet, is converted to homocysteine, which is condensed with serine by cystathionine β-synthase (CBS) to generate cystathionine. Cystathionine is acted on by cystathionine γ-lyase (CSE) to generate cysteine. Cysteine is utilized to generate hydrogen sulfide (H2S) by CSE and CBS. H2S can also be generated from homocysteine by CSE and CBS. Cysteine can also be converted to glutathione. In addition, cysteine aminotransferase (CAT), also known as aspartate aminotransferase (AAT) or glutamate oxaloacetate transaminase (GOT) generates 3-mercaptopyruvate from L-cysteine which is utilized by 3-mercaptopyruvate sulfurtransferase (3-MST) to generate H2S in the presence of reducing agents [99] (B) Transport of cyst(e)ine. Cysteine is imported via the excitatory amino acid transporter 3 (EAAT3) and the alanine, serine, cysteine transporter (ASCT). Its oxidized form, cystine, is transported by the transporters system xc−. The EAAT3 and ASCT transporters are Na+-dependent, whereas the system xc− is Na+-independent and Cl−-dependent and functions as an antiporter, exchanging 1 molecule of glutamate for cystine. Once inside the cell, cystine is rapidly reduced to cysteine by either thioredoxin reductase 1 (TRR1) or glutathione (GSH).