Ornithine transcarbamylase

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Human OTC
Ornithine transcarbamylase
Identifiers
Symbol	OTC OCTD
HUGO	8512
Entrez	5009
OMIM	300461
RefSeq	NM_000531
UniProt	P00480
Other data
EC number	2.1.3.3
Locus	Chr. X p21.1

Ornithine transcarbamylase (OTC) (also called ornithine carbamoyltransferase) is an enzyme that catalyzes the reaction between carbamoyl phosphate (CP) and ornithine (Orn) to form citrulline (Cit) and phosphate (P_i). In plants and microbes OTC is involved in arginine (Arg) biosynthesis, whereas in mammals it is located in the mitochondria and is part of the urea cycle.

1 Structure
2 Function
3 Deficiency
4 References

[edit] Structure

OTC is a trimer. The monomer unit has a CP-binding domain and an amino acid-binding domain. Each of the two discrete substrate-binding domains (SBDs) have an α/β topology with a central β-pleated sheet embedded in flanking α-helices.

The active sites are located at the interface between the protein monomers.

[edit] Function

The reaction mechanism of OTC.
The side chain amino group of Orn undergoes a nucleophilic attack upon the carbonyl carbon of CP, left, to form a tetrahedral transition state, middle. Charge rearrangement releases Cit and P_i, right. ^[1]

[edit] Deficiency

Main article: Ornithine transcarbamylase deficiency

If a person is deficient in OTC, ammonia levels will build up, and this will cause neurological problems. Levels of the amino acids glutamate and alanine, will be increased (as these are the amino acids that receive nitrogen from others).

Levels of urea cycle intermediates may be decreased, as carbamoyl phosphate cannot replenish the cycle. The carbamoyl phosphate instead goes into the uridine monophosphate synthetic pathway. Here orotic acid (one step of this alternative pathway) levels in the blood are increased.

A potential treatment for the high ammonia levels is to give sodium benzoate, which combines with glycine to produce hippurate, at the same time removing an ammonium group.

[edit] References

^a Mechanism of inactivation of ornithine transcarbamoylase by Ndelta -(N'-Sulfodiaminophosphinyl)-L-ornithine, a true transition state analogue? Crystal structure and implications for catalytic mechanism. J Biol Chem. 2000 Jun 30; 275: 20012-9; PubMed Free text