3-Mercaptopyruvate Sulfurtransferase Produces Hydrogen Sulfide and Bound Sulfane Sulfur in the Brain

Abstract

Hydrogen sulfide (H₂S) is a synaptic modulator as well as a neuroprotectant. Currently, pyridoxal-5′-phosphate (PLP)-dependent cystathionine β-synthase (CBS) is thought to be the major H₂S-producing enzyme in the brain. We recently found that brain homogenates of CBS-knockout mice, even in the absence of PLP, produce H₂S at levels similar to those of wild-type mice, suggesting the presence of another H₂S-producing enzyme. Here we show that 3-mercaptopyruvate sulfurtransferase (3MST) in combination with cysteine aminotransferase (CAT) produces H₂S from cysteine. In addition, 3MST is localized to neurons, and the levels of bound sulfane sulfur, the precursor of H₂S, are greatly increased in the cells expressing 3MST and CAT but not increased in cells expressing functionally defective mutant enzymes. These data present a new perspective on H₂S production and storage in the brain. Antioxid. Redox Signal. 11, 703–714.