The enzymes of the transsulfuration pathway also have the capacity to catalyze the desulf-hydration of cysteine. Recent studies demonstrate a role of the transsulfuration enzymes, cystathionine γ-lyase and cystathionine β-syn-thase, in catalyzing the desulfhydration of cysteine in brain and smooth muscle. The H2S produced from cysteine functions as a neuromodulator and smooth muscle relaxant. In glutamatergic neurons, the production of H2S by cystathionine β-synthase enhances N-methyl-D-aspartate (NMDA) receptor-mediated currents. In smooth muscle cells, H2S produced by cystathionine γ-lyase enhances the outward flux of potassium by opening potassium channels, leading to hyperpolarization of membrane potential and smooth muscle relaxation.