4.4.1.1: cystathionine gamma-lyase

This is an abbreviated version!
For detailed information about cystathionine gamma-lyase, go to the full flat file.

Reaction

Synonyms

AFUA_8G04340, C-S-lyase, C-S-lyase1, C-S-lyase2, C-S-lyase3, C-S-lyase4, cgl, CGL like protein, CS-LIKE, CSE, CSEgamma, CTH, CTT, cystalysin, cystathionase, cystathioninase, cystathionine beta/gamma-lyase, cystathionine gamma lyase, cystathionine gamma-lyase, cystathionine gamma-lyase-like protein, cystathionine-gamma-lyase, cysteine desulfhydrase, cysteine lyase, cystine desulfhydrase, dehydratase, homoserine, DES1, desulfhydrase, cysteine, EC 4.2.1.15, gamma-CTL, gamma-CTLase, gamma-cystathionase, hCSE, homoserine deaminase, homoserine deaminase-cystathionase, homoserine dehydratase, human cystathionine-gamma-lyase, L-Cys desulfhydrase, L-cysteine desulfhydrase, L-cysteine desulphydrase, L-cysteine-desulfhydrase, LCD, lyase, cystathionine gamma-, PRB-RA, Probasin-related antigen, TGME49_112930, XometC, yCGL

ECTree

     4 Lyases

         4.4 Carbon-sulfur lyases

             4.4.1 Carbon-sulfur lyases (only sub-subclass identified to date)

                4.4.1.1 cystathionine gamma-lyase

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Results	in table
12	Activating Compound
5091	AA Sequence
33	Application
1	CAS Registry Number
38	Cloned(Commentary)
81	Cofactor
7	Crystallization (Commentary)
319	Disease/ Diagnostics
34	Expression
28	General Information
2	General Stability
14	IC50 Value
183	Inhibitors
50	kcat/KM [mM/s]
1	Ki Value [mM]
112	KM Value [mM]
12	Localization
4	Metals/Ions
47	Molecular Weight [Da]
49	Natural Substrates/ Products (Substrates)
2	Organic Solvent Stability
382	Organism
11	Pathway
100	PDB ID
22	pH Optimum
8	pH Range
1	pI Value
1	Posttranslational Modification
74	Protein Variants
27	Purification (Commentary)
7	Reaction
9	Reaction Type
209	Reference
238	Source Tissue
16	Specific Activity [micromol/min/mg]
6	Storage Stability
331	Substrates and Products (Substrate)
31	Subunits
205	Synonyms
1	Systematic Name
12	Temperature Optimum [°C]
2	Temperature Range [°C]
19	Temperature Stability [°C]
61	Turnover Number [1/s]

General Information

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General Information on EC 4.4.1.1 - cystathionine gamma-lyase

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GENERAL INFORMATION

ORGANISM

UNIPROT

COMMENTARY

LITERATURE

malfunction

5 entries

metabolism

5 entries

physiological function

17 entries

additional information

Leishmania major

E9AFE7

the Leishmania major enzyme is able to rescue the wild-type phenotype of a Saccharomyces cerevisiae enzyme-null mutant

730121

malfunction

Homo sapiens

P32929

severe loss of cystathionine gamma-lyase activity is accompanied by adverse clinical effects

709969

malfunction

Rattus norvegicus

-

both hyperglycemia and hyperketonemia mediate a reduction in enzyme expression and activity, which can contribute to the impaired H2S signaling associated with diabetes. Livers from streptozotocin-treated type I diabetic rats have lower levels of enzyme protein expression, enzyme activity, reduced tissue H2S formation, and increased reactive oxygen species production compared with those of controls

730038

malfunction

Homo sapiens

-

both hyperglycemia and hyperketonemia mediate a reduction in enzyme expression and activity, which can contribute to the impaired H2S signaling associated with diabetes. Treatment with 0.025-0.035 mM H2O2, 4-8 mM acetoacetate and high D-glucose of 25 mM causes a significant decrease in enzyme protein expression, enzyme activity, and H2S levels, and an increase in intracellular reactive oxygen species production compared with those in normal controls

730038

malfunction

Homo sapiens

P32929

inhibiting the enzyme activity with propargylglycine or silencing CSE expression using an siRNA approach results in a greater reduction in cell viability under exposure to the oxidizing agent hydrogen peroxide. Cellular oxidative stress also increases significantly upon propargylglycine inhibition or enzyme knockdown. Increased sensitivity towards H2O2-induced cytotoxicity in CSE-siRNAtransfected cells is associated with a decreased glutathione concentration (GSH) and glutathione ratio (GSH/GSSG). Incubation of cells with exogenous H2S increases the GSH concentration and GSH/GSSG ratio

729168

malfunction

Rattus norvegicus Sprague-Dawley

-

both hyperglycemia and hyperketonemia mediate a reduction in enzyme expression and activity, which can contribute to the impaired H2S signaling associated with diabetes. Livers from streptozotocin-treated type I diabetic rats have lower levels of enzyme protein expression, enzyme activity, reduced tissue H2S formation, and increased reactive oxygen species production compared with those of controls

-

metabolism

Rattus norvegicus

-

CSE is a key enzyme in the pathway of cystathionine metabolism to produce endogenous H2S

708411

metabolism

Saccharomyces cerevisiae

-

cystathionine gamma-lyase catalyzes the hydrolysis of L-cystathionine in the second step of the reverse transsulfuration pathway, which converts L-homocysteine to L-Cys

729315

metabolism

Escherichia coli

-

the enzyme is involved in H2S biosynthesis

729511

metabolism

Arabidopsis thaliana

Q9M1R1

the two cysteine desulfhydrases, L-cysteine desulfhydrase and D-cysteine desulfhydrase, are mainly responsible for the degradation of cysteine in order to generate H2S, they show similar expression patterns in tissues

729125

metabolism

Arabidopsis thaliana Col-0

-

the two cysteine desulfhydrases, L-cysteine desulfhydrase and D-cysteine desulfhydrase, are mainly responsible for the degradation of cysteine in order to generate H2S, they show similar expression patterns in tissues

-

physiological function

Homo sapiens

-

CSE activity may contribute to butyrate-stimulated H2S production in WiDr cells

701750

physiological function

Arabidopsis thaliana

-

DES1 from Arabidopsis is an L-Cys desulfhydrase involved in maintaining Cys homeostasis, mainly at late developmental stages or under environmental perturbations

710321

physiological function

Homo sapiens

-

human myometrium smooth muscle cells express cystathionine beta-synthase and cystathionine gamma-lyase. Endogenous H2S generated by cystathionine beta-synthase and cystathionine gamma-lyase locally modulates the contractility of pregnant myometrium

716719

physiological function

Mus musculus

-

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

715087

physiological function

Homo sapiens

P32929

cystathionine gamma-lyase is an important enzyme responsible for endogenous H2S production in mammalian systems. Modulation of enzyme catalytic activity alters its antioxidative activity. Role of CSE in contributing to cellular antioxidative mechanisms in cell lines of peripheral tissue origin. Knockdown of CSE does not result in significant spontaneous cell death, indicating that CSE is not vital for cell survival in the cell lines studied

729168

physiological function

Arabidopsis thaliana

Q9M1R1

L-cysteine desulfhydrase is the enzyme mainly responsible for the degradation of cysteine in order to generate H2S, D-cysteine desulfhydrase, EC 4.4.1.15, is also involved. Gene expression regulation relationship to drought tolerance in Arabidopsis thaliana, protective effect of H2S against drought, and H2S induces stomatal closure, overview

729125

physiological function

Mus musculus

Q8VCN5

aortas from atherogenic apolipoprotein E knockout mice fed a high-fat diet show reduced CSEgamma mRNA expression and protein abundance

746708

physiological function

Mus musculus

Q8VCN5

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

747187

physiological function

Mus musculus

Q8VCN5

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

747006

physiological function

Homo sapiens

-

CSE/H2S significantly upregulates the expression of ATP-binding cassette transporter A1 mRNA and protein via PI3K/AKT pathway in foam cells derived from human THP-1 macrophages. The microRNA R-216a directly targets the 3' untranslated region of CSE and significantly reduces CSE and ATP-binding cassette transporter A1 expression, and also decreases the phosphorylation of PI3K and AKT. Cholesterol efflux decrease, and cholesterol levels increase in THP-1 macrophage-derived foam cells in response to treatment with miR-216a

746972

physiological function

Homo sapiens

P32929

CSEgamma expression is upregulated by pan-histone deacetylase inhibitors and by class II-specific HDAC inhibitors, but not by other class-specific inhibitors. The histone deacetylase 6 selective inhibitor tubacin and histone deacetylase 6-specific siRNA increase CSEgamma expression and block oxidized LDL-mediated reductions in endothelial CSEgamma expression and CSEgamma promoter activity

746708

physiological function

Mus musculus

Q8VCN5

deficiency of cystathionine beta synthase upregulates cardiac cystathionine gamma lyase, plausibly by inducing specificity protein SP1

749340

physiological function

Mus musculus

Q8VCN5

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

746942

physiological function

Mus musculus

Q8VCN5

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

749321

physiological function

Arabidopsis thaliana

-

overexpressing Arabidopsis thaliana cystathionine gamma-synthase in Solanum tuberosum increases tuber methionine levels. Solanum tuberosum cv. Desiree plants with overexpression of Arabidopsis thaliana cystathionine gamma-synthase and endogenous methionine gamma-lyase silenced by RNA interference are morphologically normal and accumulate higher free methionine levels than either single-transgenic line

748010

physiological function

Mus musculus

Q8VCN5

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

747825

physiological function

Arabidopsis thaliana Col-0

-

L-cysteine desulfhydrase is the enzyme mainly responsible for the degradation of cysteine in order to generate H2S, D-cysteine desulfhydrase, EC 4.4.1.15, is also involved. Gene expression regulation relationship to drought tolerance in Arabidopsis thaliana, protective effect of H2S against drought, and H2S induces stomatal closure, overview

-