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Information on EC 4.4.1.1 - cystathionine gamma-lyase and Organism(s) Mus musculus and UniProt Accession Q8VCN5
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4.4.1.1 cystathionine gamma-lyaseIUBMB Comments
A multifunctional pyridoxal-phosphate protein. The enzyme cleaves a carbon-sulfur bond, releasing L-cysteine and an unstable enamine product that tautomerizes to an imine form, which undergoes a hydrolytic deamination to form 2-oxobutanoate and ammonia. The latter reaction, which can occur spontaneously, can also be catalysed by EC 3.5.99.10, 2-iminobutanoate/2-iminopropanoate deaminase. Also catalyses the conversion of L-homoserine to 2-oxobutanoate and ammonia, of L-cystine to thiocysteine, pyruvate and ammonia, and of L-cysteine to pyruvate, hydrogen sulfide and ammonia.
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Word Map
- 4.4.1.1
- sulfide
- h2s
- nahs
- beta-synthase
- sulfur
- homocysteine
-
transsulfuration
- pyridoxal
- propargylglycine
- dl-propargylglycine
-
gasotransmitter
- cystathionine-beta-synthase
- sulfurtransferase
-
gaseous
- 3-mercaptopyruvate
-
sulfur-containing
- hydrosulfide
- treponema
- hyperhomocysteinemia
-
adenosyltransferase
- l-methionine
-
desulfuration
- glibenclamide
-
beta-lyase
- denticola
-
vasorelaxation
- hypotaurine
- rhodanese
- persulfide
- alpha-ketobutyrate
- d-cysteine
- ppg
-
s-sulfhydration
-
h2s-producing
-
h2s-generating
- medicine
-
cowden
-
gamma-synthase
- synthesis
-
sulfhydrylase
- analysis
-
aminooxyacetic
- o-acetylserine
-
h2s-induced
-
remethylation
- agriculture
-
cysteinesulfinate
- nutrition
- l-homoserine
- biotechnology
- cys3
-
aldimine
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
Synonyms
cystathionine gamma-lyase, cystathionase, gamma-cystathionase, cystathionine-gamma-lyase, cs-like, cysteine desulfhydrase, l-cysteine desulfhydrase, cystalysin, cystathionine gamma lyase, prb-ra, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CSE
-
-
cystalysin
-
-
-
-
cystathionase
-
-
-
-
cystathioninase
-
-
-
-
cystathionine gamma-lyase
cysteine desulfhydrase
cysteine lyase
-
-
-
-
cystine desulfhydrase
-
-
-
-
dehydratase, homoserine
-
-
-
-
desulfhydrase, cysteine
-
-
-
-
gamma-CTL
-
-
-
-
gamma-cystathionase
homoserine deaminase
-
-
-
-
homoserine deaminase-cystathionase
-
-
-
-
homoserine dehydratase
-
-
-
-
lyase, cystathionine gamma-
-
-
-
-
PRB-RA
-
-
-
-
Probasin-related antigen
-
-
-
-
cystathionine gamma-lyase
-
-
-
-
cysteine desulfhydrase
-
-
-
-
gamma-cystathionase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
L-cystathionine cysteine-lyase (deaminating; 2-oxobutanoate-forming)
A multifunctional pyridoxal-phosphate protein. The enzyme cleaves a carbon-sulfur bond, releasing L-cysteine and an unstable enamine product that tautomerizes to an imine form, which undergoes a hydrolytic deamination to form 2-oxobutanoate and ammonia. The latter reaction, which can occur spontaneously, can also be catalysed by EC 3.5.99.10, 2-iminobutanoate/2-iminopropanoate deaminase. Also catalyses the conversion of L-homoserine to 2-oxobutanoate and ammonia, of L-cystine to thiocysteine, pyruvate and ammonia, and of L-cysteine to pyruvate, hydrogen sulfide and ammonia.
CAS REGISTRY NUMBER
COMMENTARY
9012-96-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-cystathionine + H2O
L-cysteine + 2-oxobutanoate + NH3
-
-
-
-
?
L-cystathionine + H2O
L-homocysteine + pyruvate + NH3
-
-
-
-
?
L-cysteine + H2O
sulfide + NH3 + pyruvate
-
-
-
-
?
L-cysteine + H2O
sulfide + NH3 + pyruvate
-
-
measurement of hydrogen sulfide production
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
calcium-calmodulin
-
catalytic activity of pure CSE is increased more than 2fold by calcium and calmodulin, but not by either substance alone
-
additional information
-
glucose (10 or 20 mM) increases the cystathionine-gamma-lyase expression in the beta-cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
-
-
predominantly localized to the endothelial layer of blood vessels
-
with a decreasing activity in tail artery, aorta and mesenteric arteries
-
in the brain, where CSE levels are low, localizations are predominantly in white matter
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
Mice with a targeted deletion of the CSE gene fed a cysteine-limited diet exhibit growth retardation, decreased levels of cysteine, glutathione, and H2S, and increased plasma homocysteine level. Histological examinations of liver do not reveal any abnormality and plasma levels of aspartate aminotransferase, alanine aminotransferase, and albumin are normal in these animals. No CSE-KO mice survive after 12 weeks of feeding with the cysteine-limited diet. Supplementation of H2S to the CSE-KO mice fails to reverse the aforementioned abnormalities. Supplementation of cysteine in the drinking water of the CSE-KO mice significantly increases plasma cysteine and glutathione levels. This eventually leads to an increase in body weight and rescues the animals from death
physiological function
aortas from atherogenic apolipoprotein E knockout mice fed a high-fat diet show reduced CSEgamma mRNA expression and protein abundance
physiological function
CSE expression and H2S production are increased during adipocyte differentiation, and the pattern of CSE mRNA expression is similar to that of CCAAT/enhancer-binding protein C/EBPbeta and C/EBPdelta, key regulators for adipogenesis. High fat diet-induced fat mass is lost in CSE deficient mice
physiological function
CSE-H2S is a dominant H2S generating system in osteoclasts, while cystathionine synthase beta does not generate H2S. A significant increase in CSE mRNA expression and H2S production is observed in periodontal ligament tissues after 3 days of mechanical loading. CSE gene knockout leads to a significant reduction in the number of maxillary osteoclasts and in the amount of tooth movement. The expression of IL-1, IL-6 and TNF-alpha is lower in CSE-/- mice after mechanical loading. Application of the H2S donor GYY4137 increases the number of RANKL-induced osteoclasts, the number of osteoclasts in periodontal tissues and tooth movement distance in CSE-/- mice
physiological function
deficiency of cystathionine beta synthase upregulates cardiac cystathionine gamma lyase, plausibly by inducing specificity protein SP1
physiological function
in an in vitro model of disturbed flow, laminar flow significantly reduces CSE expression in vitro, and only disturbed flow regions show discernable CSE protein expression in vivo. CSE expression in disturbed flow regions critically regulates both endothelial activation and flow-dependent vascular remodeling, in part through altered NO availability
physiological function
levels of serum creatinine and renal expression of acute kidney injury marker proteins are equivalent between Cth deficient and control mice. Renal ischemia/reperfusion injury causes less renal tubular damage in Cth deficient mice. The renal population of infiltrated granulocytes/macrophages is equivalent in these mice. Renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in renal ischemia/reperfusion injury are lower after renal ischemia/reperfusion injury in Cth deficient mice
physiological function
unilateral ureteral obstruction of wild-type mice reduces the expression of H2S-producing enzymes, CSE, cystathionine beta-synthase, and 3-mercaptopyruvate sulfurtransferase in the obstructed kidneys, resulting in decreased H2S and GSH levels. CSE gene deletion lowers H2S and GSH levels in the kidneys and exacerbates the decrease in H2S and GSH levels and increase in superoxide formation and oxidative damage to proteins, lipids, and DNA in the kidneys after unilateral ureteral obstruction, accompanied by greater kidney fibrosis, deposition of extracellular matrixes, expression of alpha-smooth muscle actin, tubular damage, and infiltration of inflammatory cells. CSE gene deletion exacerbates mitochondrial fragmentation and apoptosis of renal tubule cells after unilateral ureteral obstruction
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CGL_MOUSE
398
0
43567
Swiss-Prot
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
CSE-/- mice and CSE-/+ mice, mice genetically deficient in this enzyme display marked hypertension, comparable to that of eNOS-/- mice
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
aortas from atherogenic apolipoprotein E knockout mice fed a high-fat diet show reduced CSEgamma mRNA expression and protein abundance
CSE expression and H2S production are increased during adipocyte differentiation, and the pattern of CSE mRNA expression is similar to that of CCAAT/enhancer-binding protein C/EBPbeta and C/EBPdelta, key regulators for adipogenesis. C/EBPbeta and gamma bind to the CCAAT box in CSE promoter and stimulate CSE gene transcription
presence of homocysteine upregulates cystathionine gamma lyase but downregulates cystathionine beta synthase whereas H2S-donor Na2S/GYY4137 downregulates cystathionine gamma lyase but upregulates cystathionine beta. The Na2S-treatment downregulates specificity protein-1, an inducer for cystathionine gamma lyase, and upregulates microRNA miR-133a that targets specificity protein-1, and inhibits cardiomyocytes hypertrophy. In the homocysteine-treated cardiomyocytes, cystathionine beta synthase and miR-133a are downregulated and hypertrophy is induced
0.001 mg/ml lipopolysaccharide stimulates the CSE mRNA and protein levels 2.5fold, L-arginine (0.1-1 mM) dose-dependently enhances CSE mRNA and protein expression in lipopolysaccharide-treated primary macrophages
-
CSE activity and protein levels in the colonic tissue do not notably change in the mice with colitis
-
dexamethasone (0.001 mM) causes an about 85% decrease in CSE mRNA and 95% decrease in CSE protein levels, 1 mM NG-nitro-L-arginine methyl ester decreases lipopolysaccharide-induced CSE expression in macrophages
-
either the activity or protein expression of pancreatic CSE increase after the development of caerulein-induced pancreatitis in mice
-
higher rate of H2S production corresponds to an up-regulation of CSE expression in liver and kidney
-
mice that undergo 30 min of renal ischaemia and 24 h of reperfusion exhibit a significant increase in the expression of cystathionine gamma-lyase protein in the kidney
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
inhibition of hydrogen sulfide synthesis attenuates chemokine production and protects mice against acute pancreatitis and associated lung injury
medicine
-
CSE is not associated with dextran sulfate sodium-induced colitis in mice
synthesis
additional information
-
H2S is a physiologic vasodilator and regulator of blood pressure
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bikel, I.; Pavlatos, T.N.; Livingston, D.M.
Purification and subunit structure of mouse liver cystathionase
Arch. Biochem. Biophys.
186
168-174
1978
Mus musculus
Ishii, I.; Akahoshi, N.; Yu, X.N.; Kobayashi, Y.; Namekata, K.; Komaki, G.; Kimura, H.
Murine cystathionine gamma-lyase: complete cDNA and genomic sequences, promoter activity, tissue distribution and developmental expression
Biochem. J.
381
113-123
2004
Mus musculus (Q8VCN5), Mus musculus
Okuno, T.; Motobayashi, S.; Ueno, H.; Nakamuro, K.
Identification of mouse selenomethionine alpha,gamma-elimination enzyme: cystathionine gamma-lyase catalyzes its reaction to generate methylselenol
Biol. Trace Elem. Res.
108
245-257
2005
Mus musculus
Okuno, T.; Ueno, H.; Nakamuro, K.
Cystathionine gamma-lyase contributes to selenomethionine detoxification and cytosolic glutathione peroxidase biosynthesis in mouse liver
Biol. Trace Elem. Res.
109
155-171
2006
Mus musculus
Akahoshi, N.; Izumi, T.; Ishizaki, Y.; Ishii, I.
Differential induction of cystathionine gamma-lyase in the livers and kidneys of mouse dams during gestation and lactation
Biol. Pharm. Bull.
29
1799-1802
2006
Mus musculus, Rattus norvegicus
Pong, W.W.; Stouracova, R.; Frank, N.; Kraus, J.P.; Eldred, W.D.
Comparative localization of cystathionine beta-synthase and cystathionine gamma-lyase in retina: differences between amphibians and mammals
J. Comp. Neurol.
505
158-165
2007
Ambystoma tigrinum, Mus musculus
Diwakar, L.; Ravindranath, V.
Inhibition of cystathionine-gamma-lyase leads to loss of glutathione and aggravation of mitochondrial dysfunction mediated by excitatory amino acid in the CNS
Neurochem. Int.
50
418-426
2007
Homo sapiens, Mus musculus
Kaneko, Y.; Kimura, T.; Taniguchi, S.; Souma, M.; Kojima, Y.; Kimura, Y.; Kimura, H.; Niki, I.
Glucose-induced production of hydrogen sulfide may protect the pancreatic beta-cells from apoptotic cell death by high glucose
FEBS Lett.
583
377-382
2009
Mus musculus
Linden, D.R.; Sha, L.; Mazzone, A.; Stoltz, G.J.; Bernard, C.E.; Furne, J.K.; Levitt, M.D.; Farrugia, G.; Szurszewski, J.H.
Production of the gaseous signal molecule hydrogen sulfide in mouse tissues
J. Neurochem.
106
1577-1585
2008
Mus musculus, Mus musculus C57/BL6
Tamizhselvi, R.; Moore, P.K.; Bhatia, M.
Inhibition of hydrogen sulfide synthesis attenuates chemokine production and protects mice against acute pancreatitis and associated lung injury
Pancreas
36
e24-e31
2008
Mus musculus (Q8VCN5)
Yang, G.; Wu, L.; Jiang, B.; Yang, W.; Qi, J.; Cao, K.; Meng, Q.; Mustafa, A.K.; Mu, W.; Zhang, S.; Snyder, S.H.; Wang, R.
H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase
Science
322
587-590
2008
Mus musculus
Li, Q.; Sun. B.; Wang, X.; Jin, Z.; Zhou, Y.; Dong, L.; Jiang, L.H.; Rong, W.
A crucial role for hydrogen sulfide in oxygen sensing via modulating large conductance calcium-activated potassium channels
Antioxid. Redox Signal.
12
1179-1189
2010
Mus musculus
Mancardi, D.; Penna, C.; Merlino, A.; Del Soldato, P.; Wink, D.A.; Pagliaro, P.
Physiological and pharmacological features of the novel gasotransmitter: hydrogen sulfide
Biochim. Biophys. Acta
87
864-872
2009
Mus musculus
Zhu, X.Y.; Liu, S.J.; Liu, Y.J.; Wang, S.; Ni, X.
Glucocorticoids suppress cystathionine gamma-lyase expression and H2S production in lipopolysaccharide-treated macrophages
Cell. Mol. Life Sci.
67
1119-1132
2010
Mus musculus
Martin, G.R.; McKnight, G.W.; Dicay, M.S.; Coffin, C.S.; Ferraz, J.G.; Wallace, J.L.
Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract
Dig. Liver Dis.
42
103-109
2010
Homo sapiens, Mus musculus, Rattus norvegicus
Tripatara, P.; Patel, N.S.; Brancaleone, V.; Renshaw, D.; Rocha, J.; Sepodes, B.; Mota-Filipe, H.; Perretti, M.; Thiemermann, C.
Characterisation of cystathionine gamma-lyase/hydrogen sulphide pathway in ischaemia/reperfusion injury of the mouse kidney: an in vivo study
Eur. J. Pharmacol.
606
205-209
2009
Mus musculus
Nishimura, S.; Fukushima, O.; Ishikura, H.; Takahashi, T.; Matsunami, M.; Tsujiuchi, T.; Sekiguchi, F.; Naruse, M.; Kamanaka, Y.; Kawabata, A.
Hydrogen sulfide as a novel mediator for pancreatic pain in rodents
Gut
58
762-770
2009
Mus musculus, Rattus norvegicus
Gadalla, M.M.; Snyder, S.H.
Hydrogen sulfide as a gasotransmitter
J. Neurochem.
113
14-26
2010
Mus musculus
Tyagi, N.; Givvimani, S.; Qipshidze, N.; Kundu, S.; Kapoor, S.; Vacek, J.C.; Tyagi, S.C.
Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice
Neurochem. Int.
56
301-307
2010
Mus musculus
Kandil, S., Brennan, L., McBean, G.J.
Glutathione depletion causes a JNK and p38MAPK-mediated increase in expression of cystathionine-gamma-lyase and upregulation of the transsulfuration pathway in C6 glioma cells
Neurochem. Int.
56
611-619
2010
Homo sapiens, Mus musculus, Rattus norvegicus
Taniguchi, E.; Matsunami, M.; Kimura, T.; Yonezawa, D.; Ishiki, T.; Sekiguchi, F.; Nishikawa, H.,; Maeda, Y.; Ishikura, H.; Kawabata, A.
Rhodanese, but not cystathionine-gamma-lyase, is associated with dextran sulfate sodium-evoked colitis in mice: a sign of impaired colonic sulfide detoxification?
Toxicology
264
96-103
2009
Mus musculus, Rattus norvegicus
Mani, S.; Yang, G.; Wang, R.
A critical life-supporting role for cystathionine ?-lyase in the absence of dietary cysteine supply
Free Radic. Biol. Med.
50
1280-1287
2011
Mus musculus
Leucker, T.M.; Nomura, Y.; Kim, J.H.; Bhatta, A.; Wang, V.; Wecker, A.; Jandu, S.; Santhanam, L.; Berkowitz, D.; Romer, L.; Pandey, D.
Cystathionine gamma-lyase protects vascular endothelium a role for inhibition of histone deacetylase 6
Am. J. Physiol. Heart Circ. Physiol.
312
H711-H720
2017
Homo sapiens (P32929), Mus musculus (Q8VCN5)
Yuan, S.; Yurdagul, A.; Peretik, J.M.; Alfaidi, M.; Al Yafeai, Z.; Pardue, S.; Kevil, C.G.; Orr, A.W.
Cystathionine gamma-lyase modulates flow-dependent vascular remodeling
Arterioscler. Thromb. Vasc. Biol.
38
2126-2136
2018
Mus musculus (Q8VCN5)
Mo, S.; Hua, Y.
Cystathionine gamma lyase-H2S contributes to osteoclastogenesis during bone remodeling induced by mechanical loading
Biochem. Biophys. Res. Commun.
501
471-477
2018
Mus musculus (Q8VCN5)
Yang, G.; Ju, Y.; Fu, M.; Zhang, Y.; Pei, Y.; Racine, M.; Baath, S.; Merritt, T.J.S.; Wang, R.; Wu, L.
Cystathionine gamma-lyase/hydrogen sulfide system is essential for adipogenesis and fat mass accumulation in mice
Biochim. Biophys. Acta
1863
165-176
2018
Mus musculus (Q8VCN5)
Han, S.J.; Noh, M.R.; Jung, J.M.; Ishii, I.; Yoo, J.; Kim, J.I.; Park, K.M.
Hydrogen sulfide-producing cystathionine gamma-lyase is critical in the progression of kidney fibrosis
Free Radic. Biol. Med.
112
423-432
2017
Mus musculus (Q8VCN5)
Marko, L.; Szijarto, I.A.; Filipovic, M.R.; Kassmann, M.; Balogh, A.; Park, J.K.; Przybyl, L.; Ndiaye, G.; Kraemer, S.; Anders, J.; Ishii, I.; Mueller, D.N.; Gollasch, M.
Role of cystathionine gamma-lyase in immediate renal impairment and ionflammatory response in acute ischemic kidney injury
Sci. Rep.
6
27517
2016
Mus musculus (Q8VCN5)
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