Enzyme - Ornithine carbamoyltransferase

Alternative Name(s)
  • Citrulline phosphorylase.
  • OTC.
  • OTCase.
  • Ornithine transcarbamylase.

Catalytic Activity

rbamoyl phosphate + L-ornithine = H(+) + L-citrulline + phosphate


There are no Cofactors for this Enzyme

Reaction Mechanism

    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.

    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.


    The products of the reaction.

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

Associated Proteins

Protein name Organism
Ornithine carbamoyltransferase subunit I Escherichia coli (strain K12)
Ornithine carbamoyltransferase 1, anabolic Pseudomonas savastanoi pv. phaseolicola
Ornithine carbamoyltransferase subunit F Escherichia coli (strain K12)
Ornithine carbamoyltransferase 1, catabolic Streptococcus agalactiae serotype III (strain NEM316)
Ornithine carbamoyltransferase, chloroplastic Mouse-ear cress