Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Enzyme
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Query: EC:4.2.1.22 (
cystathionine beta-synthase
)
965
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Nitric oxide (NO) and carbon monoxide (CO) are well established as messenger molecules throughout the body, gasotransmitters, based on striking alterations in mice lacking the appropriate biosynthetic enzymes. Hydrogen sulfide (H(2)S) is even more chemically reactive, but until recently there was little definitive evidence for its physiologic formation.
Cystathionine beta-synthase
(
EC 4.2.1.22
), and cystathionine gamma-lyase (
CSE
; EC 4.4.1.1), also known as cystathionine, can generate H(2)S from cyst(e)ine. Very recent studies with mice lacking these enzymes have established that
CSE
is responsible for H(2)S formation in the periphery, while in the brain
cystathionine beta-synthase
is the biosynthetic enzyme. Endothelial-derived relaxing factor activity is reduced 80% in the mesenteric artery of mice with deletion of
CSE
, establishing H(2)S as a major physiologic endothelial-derived relaxing factor. H(2)S appears to signal predominantly by S-sulfhydrating cysteines in its target proteins, analogous to S-nitrosylation by NO. Whereas S-nitrosylation typically inhibits enzymes, S-sulfhydration activates them. S-nitrosylation basally affects 1-2% of its target proteins, while 10-25% of H(2)S target proteins are S-sulfhydrated. In summary, H(2)S appears to be a physiologic gasotransmitter of comparable importance to NO and carbon monoxide.
...
PMID:Hydrogen sulfide as a gasotransmitter. 2006 86
Hydrogen sulfide (H
2
S) is endogenously synthesized from l-cysteine in reactions catalyzed by
cystathionine beta-synthase
(CBS,
EC 4.2.1.22
) and gamma-cystathionase (
CSE
, EC 4.4.1.1). The role of 3-mercaptopyruvate sulfurtransferase (MPST, EC 2.8.1.2) in H
2
S generation is also considered; it could be important for tissues with low CTH activity, e.g. cells of the nervous system. The expression and activity of CBS, CTH, and MPST were detected in the human glioblastoma-astrocytoma (U-87 MG) and neuroblastoma (SHSY5Y) cell lines. In both cell lines, the expression and activity of MPST were the highest among the investigated enzymes, suggesting its possible role in the generation of H
2
S. The RP-HPLC method was used to determine the concentration of cystathionine and alpha-ketobutyrate, products of the CBS- and CTH-catalyzed reactions. The difference in cystathionine levels between cell homogenates treated with totally CTH-inhibiting concentrations of dl-propargylglycine and without the inhibitor was used to evaluate the activity of CBS. The higher expression and activity of CBS, CTH and MPST in the neuroblastoma cells were associated with more intensive generation of H
2
S in the presence of 2 mM cysteine. A threefold higher level of sulfane sulfur, a potential source of hydrogen sulfide, was detected in the astrocytoma cells in comparison to the neuroblastoma cells.
...
PMID:Hydrogen sulfide generation from l-cysteine in the human glioblastoma-astrocytoma U-87 MG and neuroblastoma SHSY5Y cell lines. 2829 44
Hydrogen sulfide has emerged as an important gaseous signaling molecule and a regulator of critical biological processes. However, the physiological significance of hydrogen sulfide metabolites such as persulfides, polysulfides, and other reactive sulfur species (RSS) has only recently been appreciated. Emerging evidence suggests that these RSS molecules may have similar or divergent regulatory roles compared with hydrogen sulfide in various biological activities. However, the chemical nature of persulfides and polysulfides is complex and remains poorly understood within cardiovascular and other pathophysiological conditions. Recent reports suggest that RSS can be produced endogenously, with different forms having unique chemical properties and biological implications involving diverse cellular responses such as protein biosynthesis, cell-cell barrier functions, and mitochondrial bioenergetics. Enzymes of the transsulfuration pathway, CBS (
cystathionine beta-synthase
) and
CSE
(cystathionine gamma-lyase), may also produce RSS metabolites besides hydrogen sulfide. Moreover, CARSs (cysteinyl-tRNA synthetase) are also able to generate protein persulfides via cysteine persulfide (CysSSH) incorporation into nascently formed polypeptides suggesting a new biologically relevant amino acid. This brief review discusses the biochemical nature and potential roles of RSS, associated oxidative stress redox signaling, and future research opportunities in cardiovascular disease.
...
PMID:Reactive Sulfur Species: A New Redox Player in Cardiovascular Pathophysiology. 3213 14
