FIG. 7.

Model for CBS glutathionylation-dependent increase in the trans-sulfuration flux and H₂S production under oxidative stress conditions. (a) The trans-sulfuration enzymes, CBS and CSE also produce H₂S from cysteine and homocysteine. Under oxidative stress conditions (denoted by gray block arrows), GSH levels are initially decreased by increased oxidation of GSH, for example, by GP. Under these conditions, glutathionylation of CBS increases its activity, leading to increased cysteine and H₂S production. Cysteine is the limiting substrate for GSH synthesis catalyzed by GCL and GS. Increased trans-sulfuration flux leads to restoration of the GSH pool compromised under oxidative stress conditions. GR denotes glutaredoxin. (b) A potential mechanism for glutathionylation of CBS. Under oxidative stress conditions, Cys346 in CBS is oxidized to a sulfenic acid, which is then modified by gluthionylation, which could be catalyzed, for example, by glutaredoxin. GCL, γ-glutamylcysteine ligase; GP, glutathione peroxidase; GS, GSH synthetase.