3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain.
Hydrogen sulfide (H(2)S) is a synaptic modulator as well as a neuroprotectant. Currently, pyridoxal-5'-phosphate (PLP)-dependent cystathionine beta-synthase (CBS) is thought to be the major H(2)S-producing enzyme in the brain. We recently found that brain homogenates of CBS-knockout mice, even in the absence of PLP, produce H(2)S at levels similar to those of wild-type mice, suggesting the presence of another H(2)S-producing enzyme. Here we show that 3-mercaptopyruvate sulfurtransferase (3MST) in combination with cysteine aminotransferase (CAT) produces H(2)S from cysteine. In addition, 3MST is localized to neurons, and the levels of bound sulfane sulfur, the precursor of H(2)S, 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 H(2)S production and storage in the brain.
National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Kiyose, Tokyo, Japan.
Norihiro
N
Shibuya
Makiko
M
Tanaka
Mikiharu
M
Yoshida
Yuki
Y
Ogasawara
Tadayasu
T
Togawa
Kazuyuki
K
Ishii
Hideo
H
Kimura
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D013455:Sulfur / Q000378:metabolism*; D013466:Sulfurtransferases / Q000378:metabolism*; D000637:Transaminases / Q000378:metabolism
D017931:DNA Primers; D013455:Sulfur; D000637:Transaminases; C019968:cysteine aminotransferase; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D006862:Hydrogen Sulfide