Abstract
Hydrogen sulfide (H2S) has been considered to be a physiological mediator since the identification of endogenous sulfides in the mammalian brain. H2S is produced from L-cysteine by enzymes such as cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3MST), and cysteine aminotransferase (CAT). CSE and CAT are regulated by Ca(2+). At steady-state low intracellular concentrations of Ca(2+), CSE and the 3MST/CAT pathway produce H2S. However, after intracellular concentrations of Ca(2+) increase in stimulated cells, the production of H2S by these enzymes decreases. We recently identified a fourth pathway, by which H2S is produced from D-cysteine by the enzymes D-amino acid oxidase (DAO) and 3MST. This pathway is mainly localized in the cerebellum and the kidney. The production of H2S from D-cysteine is 80 times more efficient than that from L-cysteine in the kidney, and the administration of D-cysteine to mice ameliorates renal ischemia-reperfusion injury more effectively than L-cysteine. These results suggest that D-cysteine might be used to treat renal diseases or even increase the success of kidney transplantation. We found that H2S-derived polysulfides exist in the brain and activate transient receptor potential ankyrin-1 (TRPA1) channels 300 times more potently than H2S. Although TRPA1 channels mediate sensory transduction and respond to a variety of stimuli, including cold temperature, pungent compounds and environmental irritants, their endogenous ligand(s) has not been identified. The sulfane sulfur of polysulfides is a reactive electrophile that is readily transferred to a nucleophilic protein thiolate to generate the protein persulfide or bound sulfane sulfur by sulfhydration (as referred to as sulfuration). The bound sulfane sulfur-producing activity of polysulfides is much greater than that of H2S. This review focuses on the physiological roles of H2S and H2S-derived polysulfides as signaling molecules.
TY - JOUR
T1 - The physiological role of hydrogen sulfide and beyond.
A1 - Kimura,Hideo,
Y1 - 2014/02/01/
PY - 2013/11/29/received
PY - 2014/01/20/revised
PY - 2014/01/22/accepted
PY - 2014/2/5/entrez
PY - 2014/2/5/pubmed
PY - 2015/6/2/medline
KW - Bound sulfane sulfur
KW - H(2)S
KW - Polysulfides
KW - Sulfhydration
KW - Sulfuration
KW - TRP channels
SP - 4
EP - 10
JF - Nitric oxide : biology and chemistry
JO - Nitric Oxide
VL - 41
N2 - Hydrogen sulfide (H2S) has been considered to be a physiological mediator since the identification of endogenous sulfides in the mammalian brain. H2S is produced from L-cysteine by enzymes such as cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulfurtransferase (3MST), and cysteine aminotransferase (CAT). CSE and CAT are regulated by Ca(2+). At steady-state low intracellular concentrations of Ca(2+), CSE and the 3MST/CAT pathway produce H2S. However, after intracellular concentrations of Ca(2+) increase in stimulated cells, the production of H2S by these enzymes decreases. We recently identified a fourth pathway, by which H2S is produced from D-cysteine by the enzymes D-amino acid oxidase (DAO) and 3MST. This pathway is mainly localized in the cerebellum and the kidney. The production of H2S from D-cysteine is 80 times more efficient than that from L-cysteine in the kidney, and the administration of D-cysteine to mice ameliorates renal ischemia-reperfusion injury more effectively than L-cysteine. These results suggest that D-cysteine might be used to treat renal diseases or even increase the success of kidney transplantation. We found that H2S-derived polysulfides exist in the brain and activate transient receptor potential ankyrin-1 (TRPA1) channels 300 times more potently than H2S. Although TRPA1 channels mediate sensory transduction and respond to a variety of stimuli, including cold temperature, pungent compounds and environmental irritants, their endogenous ligand(s) has not been identified. The sulfane sulfur of polysulfides is a reactive electrophile that is readily transferred to a nucleophilic protein thiolate to generate the protein persulfide or bound sulfane sulfur by sulfhydration (as referred to as sulfuration). The bound sulfane sulfur-producing activity of polysulfides is much greater than that of H2S. This review focuses on the physiological roles of H2S and H2S-derived polysulfides as signaling molecules.
SN - 1089-8611
UR - https://www.unboundmedicine.com/medline/citation/24491257/The_physiological_role_of_hydrogen_sulfide_and_beyond_
L2 - https://linkinghub.elsevier.com/retrieve/pii/S1089-8603(14)00003-2
DB - PRIME
DP - Unbound Medicine
ER -
