Figure 1.
Transsulfuration pathway and glutathione biosynthetic pathway. The transsulfuration pathway metabolizes homocysteine to cysteine. In this pathway, cystathionine β-synthase (CBS) catalyzes the initial reaction, in which homocysteine is condensed with serine to form cystathionine. Cystathionine is subsequently metabolized to cysteine by the second enzyme, cystathionine γ-lyase (CSE). Both CBS and CSE are pyridoxal-5′-phosphate- (PLP-) dependent enzymes. The tripeptide glutathione is synthesized from glutamate, cysteine, and glycine. Glutamate-cysteine ligase (GCL) catalyzes the rate-limiting reaction by converting cysteine and glutamate to γ-glutamyl-cysteine. The second enzyme, glutathione synthase (GS), catalyzes the reaction of γ-glutamyl-cysteine and glycine to form glutathione. The equilibrium between reduced (GSH) and oxidized (GSSG) glutathione reflects the redox potential of a given tissue, with lower GSH : GSSG ratios being indicative of oxidative stress. Alternatively, CBS and CSE also mediate the desulfuration reactions which lead to hydrogen sulfide (H2S) synthesis.