Cofactors

There are no Cofactors for this Enzyme

Reaction Mechanism

ornithine carbamoyltransferase By Reference

Ornithine transcarbamoylase (OTCase) catalyses the formation of citrulline from carbamoyl phosphate (CP) and L-ornithine (ORN) in the urea cycle. Deleterious mutations in the human OTCase gene are associated with clinical hyperammonemia, neurological symptoms or even death. Approximately 140 mutations that result in OTCase-linked disorders have been identified, and several mutant enzymes have been purified and characterized biochemically.




• Summary
• Step 1
• Step 2
• Products

Here, the protein active site acts to stabilise the intermediates and transition states. The ornithine substrate binds in the neutral form. The amine group initiates a nucleophilic attach on the carbonyl of the carbamoyl phosphate substrate. This forms a tetrahedral intermediate that collapses, eliminating the phosphate product with concomitant deprotonation of the L-citrulline.

Catalytic Residues

AA	Uniprot	Uniprot Resid	PDB	PDB Resid
His	P00480	168	1oth	135
Gln	P00480	171	1oth	138
Arg	P00480	141	1oth	108
Asp	P00480	263	1oth	230
Cys	P00480	303	1oth	270
Arg	P00480	330	1oth	297

Step Components

dephosphorylation, intermediate formation, bimolecular nucleophilic addition, proton transfer, overall reactant used, unimolecular elimination by the conjugate base, intermediate collapse, overall product formed



Step 1.

The ornithine amine initiates a nucleophilic attack on the carbonyl carbon of the carbamic acid phosphate ester in an addition reaction.



Step 2.

The oxyanion collapses, eliminating phosphate, which deprotonates the newly formed secondary amine.



Products.

The products of the reaction.

View Reaction Mechanisms in M-CSA

Reaction Parameters

• Kinetic Parameters

  Organism	KM Value [mM]	Substrate	Comment
  Escherichia coli	1.4	L-ornithine	mutant enzyme D231A, at pH 8.5 and 20°C
  Giardia intestinalis	780	L-citrulline	pH 8.0, 37°C

• Temperature

  Organism	Temperature Range	Comment
  Moritella abyssi	23 - 25

• pH

  Organism	pH Range	Comment
  Listeria monocytogenes	4 - 11	activity range, anabolic and catabolic reactions
  Alnus glutinosa	6 - 9
  Pseudomonas aeruginosa	6 - 7.2	at 10 mM carbamoyl phosphate, sharp decrease in activity above
  Bacillus subtilis	6 - 8.3	approx. 50% of maximal activity at pH 6.0
  Rattus norvegicus	6.7 - 8.5	approx. 50% of maximal activity at pH 6.7 and 8.5, triethanolamine/acetate buffer

  View all in Brenda

Associated Proteins

Citations

• Catabolic Ornithine Carbamoyltransferase Activity Facilitates Growth of Staphylococcus aureus in Defined Medium Lacking Glucose and Arginine.
• Circadian oscillation expression of ornithine carbamoyltransferase and its significance in sleep disturbance.
• Ornithine carbamoyltransferase from psychrophiles to thermophiles: structural evolution of catalytic fold to accommodate physiological diversity.
• Management of Ornithine Carbamoyltransferase Deficiency with Underlying Hyperammonia Hyperinsulinemia Syndrome.
• Activity of the liver enzyme ornithine carbamoyltransferase (OTC) in blood: LC-MS/MS assay for non-invasive diagnosis of ornithine carbamoyltransferase deficiency.
• Involvement of Ornithine Carbamoyltransferase in the Progression of Chronic Hepatitis C and Liver Cirrhosis.
• Recapitulation of Skewed X-Inactivation in Female Ornithine Transcarbamylase-Deficient Primary Human Hepatocytes in the FRG Mouse: A Novel System for Developing Epigenetic Therapies.
• Investigation of ornithine carbamoyltransferase as a biomarker of liver cirrhosis.
• Arginine deiminase pathway of Tetragenococcus halophilus contributes to improve the acid tolerance of lactic acid bacteria
• [Ornithine carbamoyltransferase deficiency. A clinical case].
• Hypoosmosis alters hepatocyte mitochondrial morphology and induces selective release of carbamoyl phosphate synthetase 1.