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Information on EC 2.1.3.3 - ornithine carbamoyltransferase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
The plant enzyme also catalyses the reactions of EC 2.1.3.6 putrescine carbamoyltransferase, EC 2.7.2.2 carbamate kinase and EC 3.5.3.12 agmatine deiminase, thus acting as putrescine synthase, converting agmatine [(4-aminobutyl)guanidine] and ornithine into putrescine and citrulline, respectively.
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
oct, ornithine transcarbamylase, ornithine carbamoyltransferase, otcase, ornithine transcarbamoylase, carbamoyltransferase, ornithine carbamyl transferase, ornithine carbamyltransferase, catabolic ornithine carbamoyltransferase, rotcase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carbamoyltransferase, ornithine
-
-
-
-
carbamylphosphate-ornithine transcarbamylase
-
-
-
-
citrulline phosphorylase
-
-
-
-
L-ornithine carbamoyltransferase
-
-
-
-
L-ornithine carbamyltransferase
-
-
-
-
L-ornithine transcarbamylase
-
-
-
-
ornithine carbamyltransferase
-
-
-
-
ornithine transcarbamoylase
ornithine transcarbamylase
ornithine transcarbamylase 3
-
otcase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
carbamoyl phosphate + L-ornithine = phosphate + L-citrulline
show the reaction diagram
ping-pong reaction mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carbamoyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
carbamoyl-phosphate:L-ornithine carbamoyltransferase
The plant enzyme also catalyses the reactions of EC 2.1.3.6 putrescine carbamoyltransferase, EC 2.7.2.2 carbamate kinase and EC 3.5.3.12 agmatine deiminase, thus acting as putrescine synthase, converting agmatine [(4-aminobutyl)guanidine] and ornithine into putrescine and citrulline, respectively.
CAS REGISTRY NUMBER
COMMENTARY hide
9001-69-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
carbamoyl phosphate + L-ornithine
L-citrulline + phosphate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-ornithine
phosphate + citrulline
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-ornithine
phosphate + L-citrulline
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
carbamoyl phosphate + L-ornithine
L-citrulline + phosphate
show the reaction diagram
-
-
-
-
?
carbamoyl phosphate + L-ornithine
phosphate + L-citrulline
show the reaction diagram
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
-
dithiothreitol
-
-
L-2,4-diaminobutyric acid
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-
L-2-Amino-4-pentenoic acid
-
-
L-2-aminobutyrate
-
L-isomer
L-leucine
-
-
L-norvaline
-
-
ornithine
-
recombinant wild-type enzyme
Zn2+
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
activity increases with ionic strength up to 100 mM
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.13 - 1.24
Carbamoyl phosphate
0.36 - 0.55
L-ornithine
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40.2
-
recombinant enzyme
83.3
-
enzyme from a liver of a Reye's syndrome patient
86.5
-
enzyme from normal liver
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
7.7
-
triethanolamine buffer, 85% of maximal activity at pH 8.5, 25% of maximal activity at pH 6.8
8
-
gradual loss of activity above pH 8.5 or below pH 6.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8 - 8.5
-
approx. 85% of maximal activity at pH 6.8, approx. 25% of maximal activity at pH 8.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
inborn deficiency of OTC causes mainly urea cycle-related disorders and leads to hyperammonemic states that may become lethal. Some states of hepatotoxicity are associated woth hepatocyte disruption and release of OTC into the bloodstream
metabolism
-
the enzyme activity supports nitric oxide production in nitrergic neurons
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
OTC_HUMAN
354
0
39935
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
110000
-
gel filtration
114000
-
gel filtration, glycerol density gradient centrifugation
36500
-
3 * 36500, SDS-PAGE
38000
-
-
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
trimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
ornithine carbamoyltransferase is acetylated at lysine residues, including K88, which is also mutated in ornithine carbamoyltransferase-deficient patients. K88 acetylation decreases the affinity for carbamoyl phosphate, and the maximum velocity, whereas the Km for ornithine is not affected. K88 acetylation is regulated by both extracellular glucose and amino acid availabilit
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
complexed with the bisubstrate analog N-phosphoacetyl-L-ornithine
-
ornithine transcarbamoylase-carbamoylphosphate complex, X-ray structure at 2.4-2.6 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K88Q
-
less than 1% of wild-type activity
K88R
-
mutant retains substantial enzymatic activity
R277W
-
shows no substrate inhibition by ornithine, 70fold lower affinity for L-ornithine
additional information
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.8 - 8.2
-
120 min, 37°C, stable
485927
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
-50 - 60
-
stable
51
-
R277W mutant enzyme, 50% loss of activity
56
-
recombinant enzyme, 50% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
cetyltrimethylammonium stabilizes enzyme in crude extract against heat inactivation in presence of the detergent
-
loss of activity after the second thawing
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 20 mM Tris acetate, 2 mM EDTA, pH 7.4, 50% glycerol, no loss of activity
-
-20°C, 50% glycerol, 10 mM potassium phosphate, pH 7.0, 1 mM 2-mercaptoethanol, 4 months, no loss of activity
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-50°C, indefinitely
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme from normal liver and liver of a Reye's syndrome patient, DEAE-cellulose, hydroxylapatite, Sephadex G-200
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recombinant wild-type and R277W mutant enzyme, ammonium sulfate, delta-N-(phosphonacetyl)-L-ornithine affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
coexpression with GroES and GroEL in Escherichia coli
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stable overexpression of arginase I and ornithine transcarbamylase in HepG2 cells using a eukaryotic dual gene expression vector pBudCE4.1, the co-expression improves ammonia detoxification of the cells, improvement of HepG2 cell function, overview
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three different splicing isoforms, OTC-t1, OTC-t2, and OTC-t3, all three isoforms use a canonical AAUAAA hexamer that is predicted to fold into a hairpin secondary structure which might be exposed to the cleavage and polyadenylation specificity factor. In addition, the OTC-t1 and OTC-t2 transcripts display heterogeneity at the cleavage sites in a tissue-dependent manner. Secondary structure of the OTC mRNA polyA signals, overview
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in patients with Alzheimer's disease, ornithine carbamoyltransferase is expressed in brain, but not in controls. Ornithine carbamoyltransferase expression is strictly restricted to vascular endothelial cells. Ornithine carbamoyltransferase activity is 880% increased in the cerebrospinal fluid of probable Alzheimer's disease cases compared with controls. Rare haplotypes may be associated with the risk of Alzheimer's disease through a possible modulation of the methylation of the ornithine carbamoyltransferase promoter
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lower enzyme expression is observed in hepatocellular carcinoma cells and tissues compared with primary human hepatocytes
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biotechnology
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HepG2 is an immortalized human hepatoma cell line that has been used for research into bioartificial liver systems. However, a low level of ammonia detoxification is its biggest drawback. Stable overexpression of arginase I and ornithine transcarbamylase in HepG2 cells improves its ammonia detoxification
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pierson, D.L.; Cox, S.L.; Gilbert, B.E.
Human ornithine transcarbamylase. Purification and characterization of the enzyme from normal liver and the liver of a Reyes syndrome patient
J. Biol. Chem.
252
6464-6469
1977
Homo sapiens
Manually annotated by BRENDA team
Kalousek, F.; Francois, B.; Rosenberg, L.E.
Isolation and characterization of ornithine transcarbamylase from normal human liver
J. Biol. Chem.
253
3939-3944
1978
Homo sapiens
Manually annotated by BRENDA team
Morizono, H.; Tuchman, M.; Rajagopal, B.S.; McCann, M.T.; Listrom, C.D.; Yuan, X.; Venugopal, D.; Barany, G.; Allewell, N.M.
Expression, purification and kinetic characterization of wild-type human ornithine transcarbamylase and a recurrent mutant that produces 'late onset' hyperammonemia
Biochem. J.
322
625-631
1997
Homo sapiens
-
Manually annotated by BRENDA team
Shi, D.; Morizono, H.; Yu, X.; Tong, L.; Allewell, N.M.; Tuchman, M.
Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes
Biochem. J.
354
501-509
2001
Homo sapiens (P00480), Homo sapiens
Manually annotated by BRENDA team
Shi, D.; Morizono, H.
1.85-A resolution crystal structure of human ornithine transcarbamoylase complexed with N-phosphoacetyl-L-ornithine
J. Biol. Chem.
273
34247-34254
1998
Homo sapiens
Manually annotated by BRENDA team
Yamaguchi, S.; Brailey, L.L.; Morizono, H.; Bale, A.E.; Tuchman, M.
Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene
Hum. Mutat.
27
626-632
2006
Homo sapiens
Manually annotated by BRENDA team
Quental, R.; Azevedo, L.; Rubio, V.; Diogo, L.; Amorim, A.
Molecular mechanisms underlying large genomic deletions in ornithine transcarbamylase (OTC) gene
Clin. Genet.
75
457-464
2009
Homo sapiens
Manually annotated by BRENDA team
Tokushige, K.; Hashimoto, E.; Noto, H.; Yatsuji, S.; Tobari, M.; Torii, N.; Taniai, M.; Shiratori, K.; Murayama, H.
Clinical significance of serum ornithine carbamoyltransferase in patients with non-alcoholic steatohepatitis
Hepatol. Res.
39
939-943
2009
Homo sapiens
Manually annotated by BRENDA team
Yu, W.; Lin, Y.; Yao, J.; Huang, W.; Lei, Q.; Xiong, Y.; Zhao, S.; Guan, K.L.
Lysine 88 acetylation negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals
J. Biol. Chem.
284
13669-13675
2009
Homo sapiens
Manually annotated by BRENDA team
Bensemain, F.; Hot, D.; Ferreira, S.; Dumont, J.; Bombois, S.; Maurage, C.; Huot, L.; Hermant, X.; Levillain, E.; Hubans, C.; Hansmannel, F.; Chapuis, J.; Hauw, J.; Schraen, S.; Lemoine, Y.; Buee, L.; Berr, C.; Mann, D.; Pasquier, F.; Amouyel, P.; Lambert, J.C.
Evidence for induction of the ornithine transcarbamylase expression in Alzheimers disease
Mol. Psychiatry
14
106-116
2009
Homo sapiens
Manually annotated by BRENDA team
Sulkowska, J.I.; Sulkowski, P.; Szymczak, P.; Cieplak, M.
Stabilizing effect of knots on proteins
Proc. Natl. Acad. Sci. USA
105
19714-19719
2008
Homo sapiens (P00480)
Manually annotated by BRENDA team
Diaz-Munoz, M.; Hernandez-Munoz, R.
Molecular and biochemical features of the mitochondrial enzyme ornithine transcarbamylase: a possible new role as a signaling factor
Curr. Med. Chem.
17
2253-2260
2010
Homo sapiens
Manually annotated by BRENDA team
Lopes-Marques, M.; Pereira-Castro, I.; Amorim, A.; Azevedo, L.
Characterization of the human ornithine transcarbamylase 3 untranslated regulatory region
DNA Cell Biol.
31
427-433
2012
Homo sapiens (P00480), Homo sapiens
Manually annotated by BRENDA team
Tang, N.; Wang, Y.; Wang, X.; Zhou, L.; Zhang, F.; Li, X.; Chen, Y.
Stable overexpression of arginase I and ornithine transcarbamylase in HepG2 cells improves its ammonia detoxification
J. Cell. Biochem.
113
518-527
2012
Homo sapiens
Manually annotated by BRENDA team
Ohnishi, M.; Higuchi, A.; Matsumura, H.; Arakawa, Y.; Nakamura, H.; Nirei, K.; Yamamoto, T.; Yamagami, H.; Ogawa, M.; Gotoda, T.; Matsuoka, S.; Nakajima, N.; Sugitani, M.; Moriyama, M.; Murayama, H.
Involvement of ornithine carbamoyltransferase in the progression of chronic hepatitis C and liver cirrhosis
Int. J. Med. Sci.
14
629-638
2017
Homo sapiens
Manually annotated by BRENDA team
Bernstein, H.G.; Dobrowolny, H.; Keilhoff, G.; Steiner, J.
In human brain ornithine transcarbamylase (OTC) immunoreactivity is strongly expressed in a small number of nitrergic neurons
Metab. Brain Dis.
32
2143-2147
2017
Homo sapiens
Manually annotated by BRENDA team
He, L.; Cai, X.; Cheng, S.; Zhou, H.; Zhang, Z.; Ren, J.; Ren, F.; Yang, Q.; Tao, N.; Chen, J.
Ornithine transcarbamylase downregulation is associated with poor prognosis in hepatocellular carcinoma
Oncol. Lett.
17
5030-5038
2019
Homo sapiens
Manually annotated by BRENDA team