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Enzyme Nomenclature
Information on EC 3.5.3.1 - arginase
for references in articles please use BRENDA:EC3.5.3.1
Word Map on EC 3.5.3.1
- 3.5.3.1
- macrophage
- endothelial
-
polyamines
- inflammation
- dysfunction
- vascular
- injury
- l-ornithine
- pulmonary
- arterial
- peritoneal
- ammonia
-
bioavailability
-
immunosuppressive
- argininosuccinate
- lipopolysaccharide
-
myeloid-derived
- myeloid
- leishmania
- asthma
- airway
- putrescine
- hypertension
- monocyte
-
transcarbamylase
- urease
- spermidine
-
vasodilation
-
mdscs
- l-citrulline
- hyperammonemia
- agmatine
- dimethylarginine
- peroxynitrite
-
endothelium-dependent
-
l-name
- ng-monomethyl-l-arginine
-
binuclear
-
no-dependent
-
carbamoyltransferase
-
erectile
- amazonensis
- leishmaniasis
-
deiminase
-
no-synthase
- alpha-difluoromethylornithine
- pharmacology
- carbamoylphosphate
-
exhaled
- d-arginine
- nutrition
- medicine
- food industry
- analysis
-
dimethylaminohydrolase
- drug development
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
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EC NUMBER 
COMMENTARY 
3.5.3.1
-
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RECOMMENDED NAME
GeneOntology No.
arginase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-arginine + H2O = L-ornithine + urea
-
-
-
-
L-arginine + H2O = L-ornithine + urea
also hydrolyses alpha-N-substituted L-arginines and canavanine
-
L-arginine + H2O = L-ornithine + urea
hydrolysis via a metall-activated hydroxide mechanism, substrate binding structure
-
L-arginine + H2O = L-ornithine + urea
Asn130 and Ser137 are involved in substrate binding and catalysis
-
L-arginine + H2O = L-ornithine + urea
H141 serves as an acid/base catalyst, deprotonating the metal-bridging water molecule to generate the metal-bridging hydroxide nucleophile, and by protonating the amino group of the product to facilitate its departure
-
L-arginine + H2O = L-ornithine + urea
H141 as general acid to protonate the leaving amino group of L-ornithine during catalysis
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of linear amidines
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
L-arginine amidinohydrolase
Also hydrolyses alpha-N-substituted L-arginines and canavanine.
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CAS REGISTRY NUMBER
COMMENTARY
9000-96-8
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
no activity in Sus scrofa
in enterocytes of suckling piglets or in rapidly growing porcine placentae
-
-
enzyme additionally shows lectin function, binding to the cell wall of both homologous and heterologous algae
-
-
-
172099, 172116, 172133, 668256, 668975, 670050, 670051, 670930, 684384, 688021, 696006, 696016, 704175, 719198
-
-
and highly homologous sequence variants Q4A3J1, Q4A3J0, isoform arginase II; isoform arginase II
SwissProt
and highly homologous sequence variants Q4A4U9, Q4A3J0, isoform arginase II; isoform arginase II
SwissProt
and highly homologous sequence variants Q4A4U9, Q4A3J1, isoform arginase II; isoform arginase II
SwissProt
enzyme additionally shows lectin function, binding to the cell wall of both homologous and heterologous algae
-
-
-
172106, 172108, 172113, 172126, 654346, 654593, 667160, 668264, 670000, 684719, 685856, 686308, 686646, 687312, 696307, 697070, 697084, 699351, 713369, 735115
-
-
patients with cystic fibrosis, before and after 14 days of antibiotic treatment for pulmonary exacerbation
-
-
patients with histologically proven carcinoma of the gallbladder and 20 patients with cholecystitis
-
-
-
172116, 172129, 172131, 669122, 669638, 670422, 684384, 688998, 689301, 695491, 703632, 711600, 711659, 712701, 735115
-
-
oopherectomized animals treated with 0.5% cholesterol-enriched diet. Diet results in increase in plasma lipids, atheromatous lesions as well as expression of enzyme isoforms arginase I and II and an increase in cellular proliferation. Diet plus supplementation of 17beta-estradiol results in a decrease of atheromatous lesions and reduced expression of both enzyme isoforms and inducible NO synthase
-
-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
the disulfide bond is important for the overall stability and folding of the protein. Mutant proteins lacking the disulfide bond start to unfold at lower temperature than the wild-type. In the mutant proteins, the Tm of the holoenzyme is 4°C higher than that of the apoenzyme indicating that in the absence of the disulfide bond the metal ions have relatively larger role in the stability of the mutant proteins compared to the wild-type
physiological function
malfunction
-
arginase inhibition increases hepatic nitric oxide in HepG2 cells, and reverses the elevated mRNA expression of hepatic genes in lipid metabolism. The expression of phosphorylated 5' adenosine monophosphate-activated protein kinase alpha is increased by arginase inhibition in HepG2 cells
malfunction
-
arginase inhibition increases hepatic nitric oxide in high fat diet-fed mice and reverses the elevated mRNA expression of hepatic genes in lipid metabolism. The expression of phosphorylated 5' adenosine monophosphate-activated protein kinase alpha is increased by arginase inhibition in the mouse liver. Arginase inhibition prevents diet-induced obesity and reduces liver weight
physiological function
Capra capra
-
regulating synthesis of nitric oxide, proline, polyamine
physiological function
-
comparison of the infectivity of arg- and wild-type Plasmodium berghei by inoculation of mice using sporozoites dissected from mosquito salivary glands shows a significant reduction in infectivity in the arg- strain 40 h postinfection
physiological function
-
in arginase I-deficient bone marrow chimeric mice, following transfer of arginase I-deficient bone marrow into irradiated recipient mice, arginase I expression is not required for hematopoietic reconstitution and baseline immunity. Arginase I deficiency in bone marrow-derived cells decreases allergen-induced lung arginase by 85.8%. Arginase II-deficient mice have increased lung arginase activity following allergen challenge to a similar level to wild type mice. Bone-marrow-derived arginase I is not required for allergen-elicited sensitization, recruitment of inflammatory cells in the lung, and proliferation of cells. Allergen-induced airway hyperresponsiveness and collagen deposition are similar in arginase-deficient and wild type mice. Arginase II-deficient mice respond similarly to their control wild type mice with allergen-induced inflammation, airway hyperresponsiveness, proliferation and collagen deposition
physiological function
-
coinhibitory and costimulatory molecules PD-1 and CTLA-4 on the Gr-1+CD11b+ myeloid-derived suppression cells regulate the activity and expression of arginase I. The blockage and silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules can significantly reduce arginase I activity and expression induced with tumor-associated factor. Similar results are also observed while their ligands B7-H1 and/or CD80 are blocked or silenced. CD80 deficiency also decreases the arginase I expression and activity. Antibody blockade or silencing of PD-1, CTLA-4 or both reduces the suppressive potential of PD-1+CTLA-4+ myeloid-derived suppression cells. Blockade of PD-1, CTLA-4 or both also slows tumor growth and improves the survival rate of tumor-bearing mice
physiological function
-
ARG1 and ARG2 are enzymatically active in hormone-sensitive and hormone-refractory prostate cancer cell lines and their decreased expression by siRNA results in reduced overall arginase activity and L-arginine metabolism. The decreased ARG1 and ARG2 expression also translates with diminished LNCaP cells cell growth and increased peripheral blood mononuclear cell activation following exposure to LNCaP cells conditioned media. Interleukin-8 is also upregulated following androgen stimulation and it directly increases the expression of ARG1 and ARG2 in the absence of androgens
physiological function
the enzyme catalyzes the first committed step in the biosynthesis of polyamines that enable cell growth and survival
physiological function
-
the enzyme catalyzes the first committed step in the biosynthesis of polyamines that enable cell growth and survival
-
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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
1-nitro-3-guanidinobenzene + H2O
3-nitrobenzenamine + urea
-
synthetic chromophoric substrate, low activity
-
-
?
4-guanidino-2-nitrophenylacetic acid + H2O
4-amino-2-nitrophenylacetate + urea
-
-
-
-
?
4-guanidino-3-nitrobenzoic acid + H2O
4-amino-3-nitrobenzoate + urea
-
-
-
-
?
D-arginine + H2O
D-ornithine + urea
isoform LeARG1, 2.2% of the activity with L-arginine, LeARG2, 3.6% of the activity with L-arginine
-
-
?
L-homoarginine + H2O
L-2,6-diaminohexanoate + urea
isoform LeARG1, 14% of the activity with L-arginine, LeARG2, 13% of the activity with L-arginine
-
-
?
agmatine + H2O
1,4-diaminobutane + urea
-
for wild-type, no substrate. Hydrolysis by mutant N149D
-
-
?
agmatine + H2O
1,4-diaminobutane + urea
isoform LeARG1, 0.5% of the activity with L-arginine, LeARG2, 0.6% of the activity with L-arginine
-
-
?
agmatine + H2O
1,4-diaminobutane + urea
Vigna catjang
-
16% of the activity with L-arginine
-
-
?
canavanine + H2O
urea + NH2OCH2CH2CH(NH2)COOH
-
9.6% of the activity with L-arginine
-
-
?
canavanine + H2O
urea + NH2OCH2CH2CH(NH2)COOH
Vigna catjang
-
12.7% of the activity with L-arginine
-
-
?
L-arginine + H2O
L-ornithine + urea
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
-
enzyme is involved in acid resistance and inhibits host nitric oxide production
-
-
?
L-arginine + H2O
L-ornithine + urea
-
enzyme is involved in acid resistance and inhibits host nitric oxide production
-
-
?
L-arginine + H2O
L-ornithine + urea
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
-
enzyme is involved in net production of ornithine, a precursor of polyamines, glutamate, and proline, enzyme is also involved in regulation of nitric oxide biosynthesis by modulating arginine availability for nitric oxide synthase
-
-
?
L-arginine + H2O
L-ornithine + urea
-
enzyme is involved in regulating L-arginine bioavailability to NO synthase in human penile corpus cavernosum smooth muscle, and in clitoral corpus cavernosum and vagina, enzyme plays a role in both female and male sexual arousal
-
-
ir
L-arginine + H2O
L-ornithine + urea
-
enzyme is involved in regulation of nitric oxide biosynthesis by modulating arginine availability for nitric oxide synthase
-
-
?
L-arginine + H2O
L-ornithine + urea
-
reaction intermediate is Nomega-hydroxy-L-arginine
-
-
?
L-arginine + H2O
L-ornithine + urea
-
arginase competes with nitric oxide synthases for L-arginine as the common substrate
-
-
?
L-arginine + H2O
L-ornithine + urea
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
-
arginase competes with nitric oxide synthases for L-arginine as the common substrate
-
-
?
L-phenylalanine + H2O
2-oxo-3-phenylpropanoate + NH3
-
-
-
-
?
additional information
?
-
-
no substrate: agmatine, D-arginine, L-homoarginine, L-argininic acid, gamma-guanidinobutyric acid, beta-guanidinopropionic acid, streptomycin
-
-
-
additional information
?
-
-
isozyme selectivity in binding and substrate, products, and inhibitors
-
-
-
additional information
?
-
-
presence of arginine pools, which are accessible to NO synthase and enzyme, but not exchangeable
-
-
-
additional information
?
-
-
the wild type enzyme does not hydrolyze 1-amino-4-guanidinobutane (agmatine)
-
-
-
additional information
?
-
-
complex regulation of natural killer cell functions by arginine availability
-
-
-
additional information
?
-
hereditary defects in arginase compromise structure and catalysis, which results in an accumulation of arginine in the blood known as hyperarginemia. Arginase deficiency can also result in the accumulation of nitrogen in the form of ammonia, which results in hyperammonemia
-
-
-
additional information
?
-
-
recombinant human arginase I (rhArg-PEG), an arginine-depleting enzyme, can inhibit the growth of arginine-dependent tumors
-
-
-
additional information
?
-
-
arginase II is constitutively expressed in the airways of normal mice, whereas arginase I is undetectable in normal airways, while its expression is increased in airways of mice exposed to ovalbumin
-
-
-
additional information
?
-
-
enzyme may be involved in cellular proliferation in atherosclerosis, inhibiton of enzyme expression by 17beta-estradiol as mechanism in attenuating atherogenensis
-
-
-
additional information
?
-
-
mitochondrial isoform arginase II negatively regulates NO synthase 1 activity by limiting substrate availability in its microdomain
-
-
-
additional information
?
-
-
model cluster used to simulate the active site of arginase is built starting from the 1.7 A X-ray structure of rat liver arginase complexed with the inhibitor 2(S)-amino-6-boronohexanoic acid (ABH)
-
-
-
additional information
?
-
infection of mice with Schistosoma mansoni cercariae elevates arginase activity
-
-
-
additional information
?
-
-
infection of mice with Schistosoma mansoni cercariae elevates arginase activity
-
-
-
additional information
?
-
Vigna catjang
-
no substrate: D-arginine, L-homoarginine, L-argininic acid, gamma-guanidinobutyric acid, beta-guanidinopropionic acid, streptomycin
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
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-arginine + H2O
L-ornithine + urea
-
enzyme is involved in acid resistance and inhibits host nitric oxide production
-
-
?
L-arginine + H2O
L-ornithine + urea
-
enzyme is involved in acid resistance and inhibits host nitric oxide production
-
-
?
L-arginine + H2O
L-ornithine + urea
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
-
enzyme is involved in net production of ornithine, a precursor of polyamines, glutamate, and proline, enzyme is also involved in regulation of nitric oxide biosynthesis by modulating arginine availability for nitric oxide synthase
-
-
?
L-arginine + H2O
L-ornithine + urea
-
enzyme is involved in regulating L-arginine bioavailability to NO synthase in human penile corpus cavernosum smooth muscle, and in clitoral corpus cavernosum and vagina, enzyme plays a role in both female and male sexual arousal
-
-
ir
L-arginine + H2O
L-ornithine + urea
-
enzyme is involved in regulation of nitric oxide biosynthesis by modulating arginine availability for nitric oxide synthase
-
-
?
L-arginine + H2O
L-ornithine + urea
-
arginase competes with nitric oxide synthases for L-arginine as the common substrate
-
-
?
L-arginine + H2O
L-ornithine + urea
-
arginase competes with nitric oxide synthases for L-arginine as the common substrate
-
-
?
additional information
?
-
-
presence of arginine pools, which are accessible to NO synthase and enzyme, but not exchangeable
-
-
-
additional information
?
-
-
the wild type enzyme does not hydrolyze 1-amino-4-guanidinobutane (agmatine)
-
-
-
additional information
?
-
-
complex regulation of natural killer cell functions by arginine availability
-
-
-
additional information
?
-
P78540
hereditary defects in arginase compromise structure and catalysis, which results in an accumulation of arginine in the blood known as hyperarginemia. Arginase deficiency can also result in the accumulation of nitrogen in the form of ammonia, which results in hyperammonemia
-
-
-
additional information
?
-
-
recombinant human arginase I (rhArg-PEG), an arginine-depleting enzyme, can inhibit the growth of arginine-dependent tumors
-
-
-
additional information
?
-
-
arginase II is constitutively expressed in the airways of normal mice, whereas arginase I is undetectable in normal airways, while its expression is increased in airways of mice exposed to ovalbumin
-
-
-
additional information
?
-
-
enzyme may be involved in cellular proliferation in atherosclerosis, inhibiton of enzyme expression by 17beta-estradiol as mechanism in attenuating atherogenensis
-
-
-
additional information
?
-
-
mitochondrial isoform arginase II negatively regulates NO synthase 1 activity by limiting substrate availability in its microdomain
-
-
-
additional information
?
-
Q6TA39
infection of mice with Schistosoma mansoni cercariae elevates arginase activity
-
-
-
additional information
?
-
-
infection of mice with Schistosoma mansoni cercariae elevates arginase activity
-
-
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Co2+
Fe2+
Guanidinium chloride
-
the single mutant R308A changes to a trimeric and kinetically cooperative form, whereas the other enzyme variants are not altered
Magnesium
-
stabilizes the protein. In the absence of Mg2+, a complete loss of secondary structure is observed for certain elements
Manganese
-
the more deeply buried Mn2+ ion A is coordinated by residues His193, Asp216, Asp220 and Asp323. The second metal, Mn2+B is co-ordinated by His218, Asp216, Asp323, Asp325
Mg2+
Mn2+
Ni2+
additional information
Co2+
-
displays remarkable activity in the absence of exogenous metals, although manganese, cobalt, and nickel all improve activity. Enzyme shifts its metal preference from Ni, Co,and Mn (decreasing order) when assayed at pH 6 to Ni, Mn, and Co (decreasing order) at pH 9
Co2+
-
the Co2+- and Mn2+-reconstituted enzymes exhibit cooperative mechanism of arginine hydrolysis, and undergo self-association and activation with increasing concentrations. Co2+ ions play a more important role in the local tertiary structure of the protein than Mn2+
Co2+
metal preference in decreasing order: Co2+, Ni2+, Mn2+. Heat-activation in presence of metal ion is essential for activation of apo-enzyme
Co2+
effective activator, 144% activity at 1 mM; effective activator, 144% activity at 1 mM
Mn2+
-
displays remarkable activity in the absence of exogenous metals, although manganese, cobalt, and nickel all improve activity. Enzyme shifts its metal preference from Ni, Co,and Mn (decreasing order) when assayed at pH 6 to Ni, Mn, and Co (decreasing order) at pH 9
Mn2+
-
exogenous addition of Mn2+ results in increased sensitivity to inhibitor sodium fluoride
Mn2+
-
maximum activity at 0.1 mM, presence of Mn2+ results in increase in Vmax, and a higher sensitivity to product and L-lysine inhibition, with no change in KM-value for L-arginine
Mn2+
-
15-20% of the activity with Co2+; activates slightly, 14.6% of the activity with Co2+
Mn2+
-
the Co2+- and Mn2+-reconstituted enzymes exhibit cooperative mechanism of arginine hydrolysis, and undergo self-association and activation with increasing concentrations. Co2+ ions play a more important role in the local tertiary structure of the protein than Mn2+
Mn2+
metal preference in decreasing order: Co2+, Ni2+, Mn2+. Heat-activation in presence of metal ion is essential for activation of apo-enzyme
Mn2+
effective activator, 207% activity at 1 mM; effective activator, 207% activity at 1 mM
Mn2+
-
activates, role of weakly and tightly bound metal ions in wild-type and mutant enzymes, metal content, overview
Mn2+
-
activation. after dialysis with EDTA, wild-type and mutant H145N contain 1.1 and 1.3 Mn2+ per subunit, resp., and are hlaf-.active. Mutant H120N contains less than 0.1 Mn2+ per subunit and is inactive
Mn2+
-
increase in enzyme activity by incubation with 5 mM Mn2+ for 10 min at 60°C
Mn2+
-
a manganese wash at room temperature is the best condition to purify active enzyme, activity in the presence of 10 mM Mn2+ is at least 15fold higher than in the absence of Mn2+
Mn2+
-
dependent on, manganese-metalloenzyme, wild-type enzyme contains 1.97 mol Mn2+ per mol of subunit, mutants R308A and R308E contain 2.1 mol, and mutant R308K 1.25 mol per mol of subunit
Mn2+
-
dependent on, manganese-metalloenzyme, activates isozyme I, slightly, and isozyme II
Mn2+
-
manganese metalloenzyme, Mn2+-Mn2+ cluster in the active site of each monomer
Mn2+
-
arginase is a better biological catalyst for arginine hydrolysis when both cations are retained and a hydroxide ion is present in the active site bridging the two Mn metal centers
Ni2+
-
6-30% of the activity with Co2+; activates slightly, 6.1% of the activity with Co2+
Ni2+
metal preference in decreasing order: Co2+, Ni2+, Mn2+. Heat-activation in presence of metal ion is essential for activation of apo-enzyme
additional information
-
Fe2+, Ca2+, Mg2+, Zn2+, Cu2+ have no effect on enzyme activity
additional information
-
metalloenzyme, a metal ion is absolutely required for activity, no activation with Zn2+, Cu2+, Fe2+, Ca2+, and Mg2+
additional information
Ca2+, Na+, K+, Mg2+, and Ni2+ do not show any significant effect on enzyme activity; Ca2+, Na+, K+, Mg2+, and Ni2+ do not show any significant effect on enzyme activity
additional information
Ca2+, Na+, K+, Mg2+, and Ni2+ do not show any significant effect on enzyme activity; Ca2+, Na+, K+, Mg2+, and Ni2+ do not show any significant effect on enzyme activity
additional information
-
pairwise saturation mutagenesis of the first- and second-shell metal ligands in human arginase I shows that several metal binding ligands are actually quite tolerant to amino acid substitutions. The strict conservation of the second-shell metal binding residues in eukaryotic arginases does not reflect kinetic optimization of the enzyme during the course of evolution
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-amino-5-(1H-imidazol-2-ylamino)pentanoic acid
-
2-aminoimidazole amino acid inhibitor in which the 2-aminoimidazole moiety serves as a guanidine mimetic
(R)-2-amino-6-borono-2[1-(3,4-dichlorobenzyl)piperidin-4-yl]hexanoic acid
-
(S)-(2-boronoethyl)-L-cysteine
-
boronic acid-based transition state analogue, classical competitive inhibition at pH 7.5, slow-binding inhibition at pH 9.5
2-(5-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)hydrazinecarbothioamide
non-competitive inhibitor, 79% inhibition at 1 mM
2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid
-
2-aminoimidazole amino acid inhibitor in which the 2-aminoimidazole moiety serves as a guanidine mimetic
2-mercaptopropionate
5 mM, isoform LeARG1, 38% residual activity, LeARG2, 38% residual activity; 5 mM, isoform LeARG1, 38% residual activity, LeARG2, 38% residual activity
3-Mercaptopropionate
5 mM, isoform LeARG1, 24% residual activity, LeARG2, 26% residual activity; 5 mM, isoform LeARG1, 24% residual activity, LeARG2, 26% residual activity
5-methyl-2-(trifluoromethyl)-N-[3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
57% inhibition at 1 mM
5-methyl-7-(1H-1,2,4-triazol-1-yl)-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine
47% inhibition at 1 mM
5-methyl-7-(1H-pyrrol-1-yl)-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine
38% inhibition at 1 mM
5-methyl-7-(4-trifluoromethylphenylamine)-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine
52% inhibition at 1 mM
5-methyl-7-(pyrrolidin-1-yl)-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine
10% inhibition at 1 mM
5-methyl-N-(naphthalen-2-yl)-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
29% inhibition at 1 mM
5-methyl-N-phenyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
1% inhibition at 1 mM
7-(4-chlorophenylamine)-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine
42% inhibition at 1 mM
Chloroquine
-
inhibits arginase in a dose-dependent manner, and displays a linear competitive inhibition on sickle erythrocyte arginase
fluoride
-
substrate inhibition of liver enzyme at concentration above 4 mM, the kidney enzyme is more sensitive and is inhibited uncompetitively, at narrow L-arginie concentration, at 1 mM, preincubation with F- does not affect the enzymes
L-norvaline
-
blocks arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
Mercaptoacetate
5 mM, isoform LeARG1, 28% residual activity, LeARG2, 26% residual activity; 5 mM, isoform LeARG1, 28% residual activity, LeARG2, 26% residual activity
N-(2,6-difluorophenyl)-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
8% inhibition at 1 mM
N-(3,4-dichlorophenyl)-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
3% inhibition at 1 mM
N-(3,5-dichlorophenyl)-2,5-bis(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
47% inhibition at 1 mM
N-(3,5-dichlorophenyl)-2,5-dimethyl[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
23% inhibition at 1 mM
N-(3,5-dichlorophenyl)-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
71% inhibition at 1 mM
N-(3,5-dimethoxyphenyl)-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
39% inhibition at 1 mM
N-(3-chlorophenyl)-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
51% inhibition at 1 mM
N-(4-methoxyphenyl)-5-methyl-2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
5% inhibition at 1 mM
Nomega-nitro-L-arginine methyl ester
-
i.e. L-NAME, inhibition of enzyme from liver and colon cancer cells in vitro and in vivo
PEG-SOD
-
polyethylene glycol, covalently linked to superoxide dismutase. Significantly inhibits the arginase activity induced by cysteine-iron, indicating that oxygen species may be responsible in part for the observed increase in arginase activity
-
Polymyxin B
-
blocks arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
S-(2-boronomethyl)-L-cysteine
-
i.e. BMC, 50% inhibition at 3.8 mM, pH 7.4, or at 7.5 mM, pH 9.0
S-(2-boronomethyl)-L-homocysteine
-
i.e. BMHC, 50% inhibition at 0.35 mM, pH 7.4, or above 1 mM, pH 9.0
Woodward's reagent K
-
complete inactivation, reactivation by 0.5 M hydroxylamine. Reactivated enzyme can be inactivated again
(-)-epicatechin
-
(-)-epicatechin leads to a decreased arginase-2 mRNA expression after 24 h of incubation, in contrast a weak basal arginase-1 mRNA expression is not affected
(-)-epicatechin
-
(-)-epicatechin leads to a decreased arginase-2 mRNA expression after 24 h of incubation, in contrast a weak basal arginase-1 mRNA expression is not affected
(2S)-2-amino-3-(2-amino-1H-imidazol-5-yl)propanoic acid
-
2-aminoimidazole amino acid inhibitor in which the 2-aminoimidazole moiety serves as a guanidine mimetic
(2S)-2-amino-3-(2-amino-1H-imidazol-5-yl)propanoic acid
-
2-aminoimidazole amino acid inhibitor in which the 2-aminoimidazole moiety serves as a guanidine mimetic, significantly attenuates airways hyperresponsiveness in a murine model of allergic airways inflammation
2(S)-amino-6-boronohexanoic acid
-
boronic acid-based transition state analogue, classical competitive inhibition at pH 7.5, slow-binding inhibition at pH 9.5
2(S)-amino-6-boronohexanoic acid
Kd-value 5 nM, complete inhibition of enzyme in cytoplasmic extracts of myeloid suppressor cells by 0.05 mM
2(S)-amino-6-boronohexanoic acid
-
transition state analogue inhibitor, effect on female and male hemodynamics, overview
Ag+
20.41% residual activity at 1 mM; 20.41% residual activity at 1 mM
Ca2+
-
inhibitory to enzymic activity in presence of Mn2+, enhances lectin function of enzyme
Ca2+
-
inhibitory to enzymic activity in presence of Mn2+, enhances lectin function of enzyme
Cd2+
58.78% residual activity at 1 mM; 58.78% residual activity at 1 mM
Cd2+
-
mixed competitive inhibitor. Kidney enzyme is more sensitive to inhibition than liver enzyme. Cd2+ enhances substrate activation of kidney enzyme while still being inhibitory. Cd2+ is also inhibitory to kidney enzyme in presence of Mn2+
Cu2+
30.2% residual activity at 1 mM; 30.2% residual activity at 1 mM
Cu2+
-
56% inhibition of isozyme I, 69% inhibition of isozyme II, non-linear allosteric inhibition for isozymes I and II, inhibition is increased with isozyme I by preincubation with the metal ions, not with isozyme II
diethyl dicarbonate
-
causes a loss in ability of Mn2+ to reactivate inactive subunits of wild-type and mutant enzyme H141F, effect is reversed by hydroxylamine
diethyl dicarbonate
-
second-order rate constant of 113 per M and s for inactivation process. L-ornithine partially protects, L-ornithine plus borate completely protect
dithiothreitol
-
enzyme depleted of metal and reconstituted with Co2+, complete loss of activiy. Enzyme reconstitued with Mn2+, 20% loss of activity. Loss of catalytic activity in the wild-type protein with dithiothreitol is due to the interaction with Co2+
EDTA
-
after dialysis against EDTA and assay in the absence of Mn2+, the wild type enzyme exhibits 50% activity
EDTA
-
in contrast with R308A, the monomeric E256Q variant of the human enzyme is totally inactivated by dialysis in the presence of EDTA, leading to the suggestion that the quaternary structure could play a role in the affinity of metal binding to arginase
Fe2+
77.14% residual activity at 1 mM; 77.14% residual activity at 1 mM
Fe3+
77.14% residual activity at 1 mM; 77.14% residual activity at 1 mM
flavanol-rich cocoa
-
cocoa flavanols lower arginase-2 mRNA expression and activity
-
flavanol-rich cocoa
-
cocoa flavanols lower arginase-2 mRNA expression and activity
-
Hg2+
-
80% inhibition of isozyme I, 96% inhibition of isozyme II, non-linear allosteric inhibition for isozymes I and II, inhibition is increased with isozyme I by preincubation with the metal ions, not with isozyme II
L-ornithine
mixed type inhibition; mixed type inhibition
Nomega-hydroxy-L-arginine
mixed type inhibition; mixed type inhibition
Nomega-hydroxy-L-arginine
-
i.e. NOHA, binds to isoform arginase I with Kd of 3.6 microM
Nomega-hydroxy-L-arginine
0.2 mM, isoform LeARG1, 7% residual activity, LeARG2, 5% residual activity; 0.2 mM, isoform LeARG1, 7% residual activity, LeARG2, 5% residual activity
Nomega-hydroxy-nor-L-arginine
-
in unstimulated HUVEC cells, dose-dependent reduction of enzyme activity, maximum inhibition at 0.02 mM. In cells stimulated by thrombin with or without extracellular L-arginine, stimulation of NO synthase and NO release, with significant reduction of enzyme activity
Nomega-hydroxy-nor-L-arginine
-
i.e. nor-NOHA, binds to isoform arginase I with Kd of 517 nM, surface plasmon resonance, or Kd of 50 nM, isothermal titration calorimetry
S-(2-boronoethyl)-L-cysteine
-
inhibition results in in reduced fractional shortening, maximal rate of shortening, and relengthening of myocyte contractions
S-(2-boronoethyl)-L-cysteine
-
i.e. BEC, 50% inhibition at 0.005 mM, pH 7.4, or at 0.020 mM, pH 9.0
S-(2-boronoethyl)-L-cysteine
-
inhibition results in augmented Ca2+-dependent NO synthase activity and NO production in isolated myocytes
Zn2+
33.47% residual activity at 1 mM; 33.47% residual activity at 1 mM
additional information
-
combined polyethylene glycol, covalently linked to superoxide dismutase with a highly stable PEG-catalase, further decrease of arginase activity is observed; salicylic acid derivatives potently inhibited arginase activity. More significant inhibition of arginase activity in purified arginase-1 than in erythrocyte hemolysate, possibly due to the presence of increased extraneous macromolecular interactions in cell hemolysate than in purified enzyme
-
additional information
-
binding to lectins is inhibitory to enzymic activity, which is recovered after desorption of the lectin with alpha-D-galactose
-
additional information
-
ornithine is a poor inhibitor of isozyme type II, isozyme selectivity in binding and substrate, products, and inhibitors
-
additional information
-
arginase activity functionally inhibits nitric oxide synthase by depleting the substrate pool of L-arginine, and nitric oxide synthase activity potentially inhibits arginase by generating and releasing small amounts of the intermediate N-hydroxy-L-arginine, a competitive inhibitor of arginase, and also by generating nitric oxide itself, which can nitrosylate cysteine residues of human arginase I to modulate its activity; arginase activity functionally inhibits nitric oxide synthase by depleting the substrate pool of L-arginine, and nitric oxide synthase activity potentially inhibits arginase by generating and releasing small amounts of the intermediate N-hydroxy-L-arginine, a competitive inhibitor of arginase, and also by generating nitric oxide itself, which can nitrosylate cysteine residues of human arginase I to modulate its activity
-
additional information
-
cell treatment with anti-CD14 and anti-toll-like receptor 4 but not anti-toll-like receptor 2 antibody decreases arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells; DL-norvaline does not block arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
-
additional information
-
testing consequences of inhibiting arginase activity in vivo with NO production, lung inflammation, and lung function in both C57BL/6 and NOS2 knockout mice undergoing ovalbumin-induced airway inflammation, a mouse model of asthma
-
additional information
-
isothiourea homologues undergo rapid non-enzymic rearrangement to probably give inhibitory compouds, overview
-
additional information
-
effect of preincubation of the isozymes with metal ions, overview
-
additional information
-
ebselen does not inhibit arginase, apocynin does not affect the stability of arginase I mRNA but accelerates the decline of arginase activity when protein synthesis is inhibited by cycloheximide
-
additional information
L-lysine and diaminopimelic acid failed to block SmARG activity
-
additional information
-
binding to lectins is inhibitory to enzymic activity, which is recovered after desorption of the lectin with alpha-D-galactose
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cysteine
-
effect of cysteine on arginase activity, effect of increasing concentrations of cysteine alone or in combination with iron (II) sulfate on the enhancement of arginase activity in human sickle erythrocytes or purified arginase-1 from Bos taurus liver
dexamethasone
-
augments arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
FeSO4
-
effect of cysteine on arginase activity, effect of increasing concentrations of cysteine alone or in combination with iron (II) sulfate on the enhancement of arginase activity in human sickle erythrocytes or purified arginase-1 from Bos taurus liver
hydralazine
-
treatment with 20 mg/kg/day hydralazine for 5 weeks causes increased arginase activity in hypertensive rats
IL-4
-
interleukin IL-4, up to 16-fold stimulation of enzyme activity in RAW-264.7 cell, in combinantion with rolipram additional activation. No stimulation of enzyme in alveolar macrophages by IL-4 alone, but increase of stimulation by forskolin and 3-isobutyl-1-methylxanthine, IBMX, in presence of IL-4
-
interleukin-4
-
augments arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
-
L-arginine
-
strong substrate activation of the kidney enzyme at concentrations above 4 mM
low-density lipoprotein
-
ArgI expression is potently induced by both oxidized and acetylated low-density lipoprotein in macrophages, this effect is mediated by peroxisome proliferator-activated receptors
-
TGF-beta
-
transforming growth factor, up to 5-fold stimulation, further stimulation in combination with rolipram
-
thrombin receptor antagonist peptide
-
endothelial cell exposition to 10 U/ml thrombin receptor antagonist peptide for 4 h leads to increased arginase activity
-
lipopolysaccharide
-
lipopolysaccharide from Actinobacillus actinomycetemcomitans or Escherichia coli
lipopolysaccharide
-
0.001 mg/ml cause a 2fold increase in arginase activity and a marked increase in mRNA encoding arginase I
thrombin
-
endothelial cell exposition to 10 U/ml thrombin for 4 h leads to 1.6fold increased arginase activity
-
additional information
-
treatment with methyl jasmonate. ARGAH1 expression is lower in argah1-1 mutants compared to either wild-type or argah2-1 plants and does not increase in any genotype following methyl jasmonate treatment
-
additional information
-
rolipram increases stimulation by interleukin IL-4 and transforming growth factor beta
-
additional information
-
interferon-gamma does not augment arginase activity in Actinobacillus actinomycetemcomitans lipopolysaccharide-stimulated cells
-
additional information
-
expression of arginase I strongly correlated with the presence of lung inflammation, as quantified by differential cell counts in lung lavage, suggesting that most, or all, of the arginase I in lungs of mice exposed to ovalbumin is present in the inflammatory cells rather than in the airway epithelium
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.15
L-arginine
-
mutant D181E/S230A, activated by Co2+, pH 7.4, 37°C; mutant S230C, activated by Co2+, pH 7.4, 37°C; mutant S230D, activated by Co2+, pH 7.4, 37°C
2.5
L-arginine
-
T135S mutant, KM increases 2.5fold relatively to values measured for the wild-type enzyme
3.1
L-arginine
-
mutant S89G, Mn2+-activated, pH 5.0, 37°C, Hill coefficient 2.1
4
L-arginine
-
mutant dN-PFA-L2S, pH 8.0, 37°C; mutant dN-PFA, pH 8.0, 37°C
4.4
L-arginine
-
mutant H91A, Co2+-activated, pH 5.0, 37°C, Hill coefficient 2.3
4.8
L-arginine
-
free and chitosan-immobilized enzyme, at pH 7.0 and 40°C
5.2
L-arginine
-
mutant A92S, Mn2+-activated, pH 5.0, 37°C, Hill coefficient 1.6
5.25
L-arginine
at pH 7.0 and 30°C; at pH 7.0 and 30°C
5.9
L-arginine
-
mutant A92S, Co2+-activated, pH 5.0, 37°C, Hill coefficient 1.9; mutant S89G, Co2+-activated, pH 5.0, 37°C, Hill coefficient 2.2
6.3
L-arginine
-
mutant S88G, Co2+-activated, pH 5.0, 37°C, Hill coefficient 2.0
6.4
L-arginine
-
mutant E90A, Co2+-activated, pH 5.0, 37°C, Hill coefficient 1.7
6.7
L-arginine
-
pH 5.0, 37°C, Mn2+-activited enzyme, K0.5 value, Hill-coefficient 1.6
6.7
L-arginine
-
mutant S88G/A92S, Co2+-activated, pH 5.0, 37°C, Hill coefficient 2.0; wild-type, Mn2+-activated, pH 5.0, 37°C, Hill coefficient 1.6
8.4
L-arginine
-
pH 5.0, 37°C, Co2+-activited enzyme, K0.5 value, Hill-coefficient 2.1
8.4
L-arginine
-
wild-type, Co2+-activated, pH 5.0, 37°C, Hill coefficient 2.1
8.7
L-arginine
-
mutant S88G, Mn2+-activated, pH 5.0, 37°C, Hill coefficient 2.4
9.2
L-arginine
-
mutant S88G/A92S, Mn2+-activated, pH 5.0, 37°C, Hill coefficient 2.2
13
L-arginine
-
T135A mutant, KM is increased 13fold relatively to values measured for the wild-type enzyme
13
L-arginine
-
wild-type, pH 8.0, temperature not specified in the publication
45
L-arginine
-
mutant R404A, pH 8.0, temperature not specified in the publication
146
L-arginine
-
mutant E295R, pH 8.0, temperature not specified in the publication
57.5
L-phenylalanine
-
chitosan-immobilized enzyme, at pH 7.0 and 40°C
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.013
L-arginine
-
mutant E90A, Co2+-activated, pH 5.0, 37°C; mutant H91A, Co2+-activated, pH 5.0, 37°C
0.28
L-arginine
-
mutant S88G/A92S, Mn2+-activated, pH 5.0, 37°C; wild-type, Co2+-activated, pH 5.0, 37°C
1
L-arginine
-
mutant E295A, pH 8.0, temperature not specified in the publication
1.3
L-arginine
-
mutant E295A/R404A, pH 8.0, temperature not specified in the publication
6.7
L-arginine
-
mutant E295R, pH 8.0, temperature not specified in the publication
11.4
L-arginine
-
mutant R404A, pH 8.0, temperature not specified in the publication
24.8
L-arginine
-
wild-type, pH 8.0, temperature not specified in the publication
260
L-arginine
-
T135A mutant, is reduced 26% relative to values measured for the wild-type enzyme
350
L-arginine
-
T135S mutant, kcat is unchanged relatively to values measured for the wild-type enzyme; wild type
0.46
L-phenylalanine
-
chitosan-immobilized enzyme, at pH 7.0 and 40°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.03
L-arginine
-
mutant E295R, pH 8.0, temperature not specified in the publication
0.25
L-arginine
-
mutant R404A, pH 8.0, temperature not specified in the publication
1.9
L-arginine
-
wild-type, pH 8.0, temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.3
(2S)-2-amino-3-(2-amino-1H-imidazol-5-yl)propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.5
(2S)-2-amino-5-(1H-imidazol-2-ylamino)pentanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.017
2-(5-methyl-2-(trifluoromethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)hydrazinecarbothioamide
at pH 9.5 and 37°C
0.004
2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00015
2-(S)-amino-6-boronohexanoic acid
-
pH 9.5, 25°C, supramolecular tandem assay method
0.01
2(S)-amino-6-boronohexanoic acid
-
mutant dN-PFA, pH 8.5, 37°C
0.011
2(S)-amino-6-boronohexanoic acid
-
mutant dN-PFA, pH 7.4, 37°C
0.012
2(S)-amino-6-boronohexanoic acid
-
mutant dN-PFA, pH 8.0, 37°C
0.053
2(S)-amino-6-boronohexanoic acid
-
mutant dN-PFA-H381A, pH 8.0, 37°C