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Enzyme Nomenclature
Information on EC 3.5.3.1 - arginase
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3.5.3.1 arginaseIUBMB Comments
Also hydrolyses alpha-N-substituted L-arginines and canavanine.
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Word Map
- 3.5.3.1
- cytokine
- endothelial
- polyamines
- tnf
- necrosis
-
immunosuppressive
- bone
- myeloid
-
myeloid-derived
- l-ornithine
- peritoneal
- monocyte
- pulmonary
- lps
- arterial
- lipopolysaccharide
-
pro-inflammatory
-
mdscs
- ammonia
- microglia
- t-cells
- airway
- argininosuccinate
- hypertension
- leishmania
- asthma
- putrescine
-
transcarbamylase
-
marrow-derived
-
vasodilation
- dimethylarginine
-
endothelium-dependent
- urease
- hyperammonemia
- agmatine
-
m2-like
- l-citrulline
- leishmaniasis
-
l-name
-
tregs
- interleukin-10
-
no-dependent
-
carbamoyltransferase
- ng-monomethyl-l-arginine
-
erectile
- carbamoylphosphate
- amazonensis
- medicine
- no-synthase
- synthesis
-
il-4-induced
-
dimethylaminohydrolase
- analysis
- pharmacology
- food industry
- drug development
- nutrition
The enzyme appears in viruses and cellular organisms
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ARG
Arg I
Arg II
ARG1
ARG2
arginase
arginase 1
arginase 1a
arginase 1b
arginase 2a
arginase 2b
arginase I
arginase II
arginase-2
arginine amidinase
-
-
-
-
arginine transamidinase
-
-
-
-
canavanase
-
-
-
-
Kidney-type arginase
-
-
-
-
L-arginase
-
-
-
-
L-arginine amidino hydrolase
L-arginine amidinohydrolase
Liver-type arginase
-
-
-
-
Non-hepatic arginase
-
-
-
-
RocF
additional information
additional information
-
enzyme belongs to the arginase superfamily
-
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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 SOURCE
PATHWAYS
BRENDA
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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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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
-
the enzyme involved in urea cycle
-
-
?
L-arginine + H2O
L-ornithine + urea
-
the enzyme does not hydrolyse D-arginine and other arginine analogues (L-agmatine, L-canavanine, L-argininamide and L-homoarginine)
-
-
?
L-arginine + H2O
L-ornithine + urea
the enzyme catalyses the catabolism of L-arginine to L-ornithine and urea
-
-
?
L-arginine + H2O
L-ornithine + urea
the biosynthesis yield of L-ornithine by the purified enzyme is 36.9 g/l, and the molar yield is 97.2%
-
-
?
L-arginine + H2O
L-ornithine + urea
the biosynthesis yield of L-ornithine by the purified enzyme is 36.9 g/l, and the molar yield is 97.2%
-
-
?
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
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-
?
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 catalyzes the first committed step in the biosynthesis of polyamines
-
-
?
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-arginine + H2O
L-ornithine + urea
-
mechanism of positive cooperativity. The kinetic characterization of arginase from yeast crude extract indicates that both fermentation temperature and timing clearly affect enzymatic activity, which gradually increases after the inoculum, reaching the highest Vmax value when yeast assimilable nitrogen is nearly completely exhausted and the arginine added to the semi-synthetic grape juice is significantly consumed (approximately 40-50% of its initial level). Yeast arginase shows the best catalytic properties when alcoholic fermentation occurrs at 20°C approximately 3 days after the inoculum
-
-
?
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
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-
-
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
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-
-
additional information
?
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enzyme may be involved in cellular proliferation in atherosclerosis, inhibiton of enzyme expression by 17beta-estradiol as mechanism in attenuating atherogenensis
-
-
-
additional information
?
-
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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)
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-
-
additional information
?
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infection of mice with Schistosoma mansoni cercariae elevates arginase activity
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-
-
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 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
L-arginine + H2O
L-ornithine + urea
-
the enzyme involved in urea cycle
-
-
?
L-arginine + H2O
L-ornithine + urea
the enzyme catalyses the catabolism of L-arginine to L-ornithine and 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
-
arginase competes with nitric oxide synthases for L-arginine as the common substrate
-
-
?
L-arginine + H2O
L-ornithine + urea
arginase catalyzes the first committed step in the biosynthesis of polyamines
-
-
?
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
-
-
?
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
?
-
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+
Cd2+
chelating loosely bound Mn2+ and replacing it with a variety of bivalent metal ions including Mg2+, Zn2+, Ni2+, Hg2+, Cu2+, Co2+, Ca2+ and Cd2+ retains its enzymatic activity
Co2+
Cu2+
chelating loosely bound Mn2+ and replacing it with a variety of bivalent metal ions including Mg2+, Zn2+, Ni2+, Hg2+, Cu2+, Co2+, Ca2+ and Cd2+ retains its enzymatic activity
Fe2+
Fe3+
-
the enzyme retains 38.7% of its original activity after dialysis. In the presence of Mn2+ as a cofactor, the enzyme regains 95% of its initial activity
Guanidinium chloride
-
the single mutant R308A changes to a trimeric and kinetically cooperative form, whereas the other enzyme variants are not altered
Hg2+
chelating loosely bound Mn2+ and replacing it with a variety of bivalent metal ions including Mg2+, Zn2+, Ni2+, Hg2+, Cu2+, Co2+, Ca2+ and Cd2+ retains its enzymatic activity
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+
NaCl
the enzyme is optimally active at 100 mM NaCl, but as the salt concentration increase, the activity of the enzyme is reduced to almost half of the maximal activity but the enzyme is still partially active
Ni2+
Zn2+
additional information
Ca2+
chelating loosely bound Mn2+ and replacing it with a variety of bivalent metal ions including Mg2+, Zn2+, Ni2+, Hg2+, Cu2+, Co2+, Ca2+ and Cd2+ retains its enzymatic activity
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 enzyme retains 38.7% of its original activity after dialysis. In the presence of Mn2+ as a cofactor, the enzyme regains 95% of its initial activity
Co2+
chelating loosely bound Mn2+ and replacing it with a variety of bivalent metal ions including Mg2+, Zn2+, Ni2+, Hg2+, Cu2+, Co2+, Ca2+ and Cd2+ retains its enzymatic activity
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
Mg2+
chelating loosely bound Mn2+ and replacing it with a variety of bivalent metal ions including Mg2+, Zn2+, Ni2+, Hg2+, Cu2+, Co2+, Ca2+ and Cd2+ retains its enzymatic activity
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+
all recombinant variants are active even in the absence of added Mn2+ but express about2.5-fold increased activity in the presence of 2 mM Mn2+. After extensive dialysis against 25 mM EDTA, they became totally dependent on added Mn2+ for catalytic activity. The manganese-reactivation of all fully inactivated species followed hyperbolic kinetics
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+
-
the enzyme retains 38.7% of its original activity after dialysis. In the presence of Mn2+ as a cofactor, the enzyme regains 96% of its initial activity
Mn2+
-
maximum activity (100%) with 1 mM Mn2+. 0.5mM of Mn2+ exhibits 70% of total activity
Mn2+
two Mn2+ ions are required for the enzyme to be fully functional
Mn2+
optimum metal cofactor. The optimal concentration of Mn2+ is approximately 2 mM. When the concentration is higher than 2 mM, there is a slight drop in relative activity. The active site of L-arginase contains two Mn2+ ions (Mn2+A and Mn2+B), which are coordinated by Asp and His residues. When Mn2+ concentration increases from 0 to 10 mM, the ellipticity of L-arginase at 208 nm and 222 nm increases accordingly. The percentage of helix increases to 66% in the presence of 10 mM Mn2+. This suggests that the addition of Mn2+ can affect the structure of L-arginase by increasing the helix content of the enzyme
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+
chelating loosely bound Mn2+ and replacing it with a variety of bivalent metal ions including Mg2+, Zn2+, Ni2+, Hg2+, Cu2+, Co2+, Ca2+ and Cd2+ retains its enzymatic activity
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
Zn2+
chelating loosely bound Mn2+ and replacing it with a variety of bivalent metal ions including Mg2+, Zn2+, Ni2+, Hg2+, Cu2+, Co2+, Ca2+ and Cd2+ retains its enzymatic activity
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
-
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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INHIBITOR
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
(DL)-2-amino-6-borono-2-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-hexanoic acid
-
-
-
(R)-2-amino-6-borono-2-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-hexanoic acid
-
-
(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
5,5'-dithiobis (2-nitrobenzoic acid)
1 mM, 23% loss of 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
homoarginine
-
at 2 mM arginine, 18% and 94% inhibition of arginase 2 is observed by homoarginine at the concentration of 1 and 10 mM. At 0.1 mM arginine, the conversion of arginine to ornithine by arginase 2 is inhibited by 47% and 88% in the presence of 1 mM and 10 mM homoarginine. No significant inhibition of arginase 2 is observed at physiological homoarginine concentrations; at Km concentration (3 mM) of the substrate arginine, 1 mM homoarginine inhibits arginase 1 activity by 14%, whereas a concentration of 10 mM results in 50% inhibition of the enzyme. At 0.1 mM arginine, arginase 1 inhibition by 1 mM and 10 mM homoarginine is 30% and 76%, respectively. No significant inhibitory effects of arginase 1 activity are observed with physiological concentrations of homoarginine, 0.001-0.01 mM
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
Mn2+
-
the rate of arginase 1-mediated ornithine formation from L-arginine is 20% higher in absence of Mn2+ supplementation; the rate of arginase 1-mediated ornithine formation from L-arginine is 20% higher in absence of Mn2+ supplementation
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
spermidine
-
inhibition in a dose-dependent fashion below 5 mM and above 25 mM
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
caffeic acid
-
inhibiting arginase activity by caffeic acid and chlorogenic acid might be a possible mechanism by which they exert their cardio-protective effect
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+
chlorogenic acid
-
inhibiting arginase activity by caffeic acid and chlorogenic acid might be a possible mechanism by which they exert their cardio-protective effect
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
lysine
-
at 2 mM arginine, 42% and 67% inhibition of arginase 2 is observed by lasine at 1 mM and 10 mM. At 0.1 mM arginine, the conversion of arginine to ornithine by arginase 2 is inhibited by 44% and 88% in the presence of 1 mM and 10 mM lysine. No significant inhibition of arginase 2 is observed at physiological lysine concentrations; at concentrations of 1 and 10 mM, 39% and 78% inhibition of arginase 1 activity at Km concentration (3 mM) of the substrate arginine, and 44% and 81% inhibition at physiological arginine concentrations. No significant inhibitory effects of arginase 1 activity are observed with physiological concentrations of lysine, 0.1-1.0 mM
NaCl
the enzyme is optimally active at 100 mM NaCl, but as the salt concentration increased, the activity of the enzyme was reduced to almost half of the maximal activity but the enzyme was still partially active
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
-
arginase inhibition is unlikely to play a significant role in the cardio-protective effects of homoarginine; arginase inhibition is unlikely to play a significant role in the cardio-protective effects of homoarginine
-
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
1-amino-6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid methyl ester
-
activity is enhanced in the presence of the dihydropyrimidine derivative
-
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
-
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
-
L-arginine
the enzyme is kinetically cooperative and the commonly detected hyperbolic behavior results from binding of L-arginine as a typical allosteric activator
L-arginine
-
strong substrate activation of the kidney enzyme at concentrations above 4 mM
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
1.9
L-arginine
-
arginase 2, pH and temperature not specified in the publication
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
3.3
L-arginine
-
arginase 1, pH and temperature not specified in the publication
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
5.9
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
7.14
L-arginine
-
in absence of dihydropyrimidine derivative, pH and temperature not specified in the publication
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
300
L-arginine
pH 9.5, 55°C, mutant enzyme E256A; pH 9.5, 55°C, mutant enzyme E256A/E278A
350
L-arginine
-
T135S mutant, kcat is unchanged relatively to values measured for the wild-type enzyme; wild type
400
L-arginine
pH 9.5, 55°C, mutant enzyme D199N; pH 9.5, 55°C, mutant enzyme E256Q
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