Ornithine carbamoyltransferase is an enzyme found in the mitochondrion of the liver and participates in the urea cycle. It is a catalyst facilitating the reaction between ornithine and carbamoyl phosphate, producing citrulline and phosphate. An X-linked recessive genetic disease resulting in a deficiency of this enzyme is particularly devastating, leading to toxic buildup of ammonia in the body, causing neurological damage, coma and even death.
Significance
As a key component of the urea cycle, which processes ammonia into urea in mammals, ornithine carbamoyltransferase (also known as ornithine transcarbamoylase) performs an essential function in the body. Ammonia is produced when digesting high-protein foods, or when the body is running low on energy and begins digesting its own proteins. Because ammonia is highly toxic, especially neurologically, a missing link in the urea cycle can have devastating consequences. This same compound is also found in plants and microbes, where it is involved in arginine biosynthesis. This amino acid is also found in the urea cycle.
Function
Ornithine carbamoyltransferase functions as a catalyst, meaning it participates in the reaction but emerges unchanged. Specifically, from the mitochondrion of the liver, it brings together ornithine and carbamoyl phosphate and releases phosphate and citrulline. As one of the first steps in the cycle following introduction of ammonia (carbamoyl phosphate is created from ammonia and carbon dioxide), a deficiency in this enzyme is a direct cause of hyperammonemia, or high blood concentrations of the compound.
Features
Ornithine carbamoyltransferase is a trimer, or a molecule formed from three identical "monomers;" in this case, three identical proteins, each of which has a binding site for carbamoyl phosphate, and one for an amino acid. In the trimer, the active sites are located in the center, where the three monomers come together. Its name comes from its function, and so refers to the two types of binding sites, rather than the structure of the enzyme itself.
Considerations
A rare genetic disorder, occurring in about 1 out of 80,000 live births, results in a condition known as ornithine transcarbamoylase deficiency, or OTCD. In the severe form of this disorder, symptoms begin about a day after birth, and if an accurate diagnosis is not made almost immediately (which is difficult, given the variability of the symptoms, and the overlap with many more common disorders), the infant will be dead within a week. More mild forms give later onset and longer windows to make a diagnosis and still have a decent prognosis.
Prevention/Solution
While the severe form of OCTD does not seem to leave much room for medical science to work with, work on therapy for the milder forms of this X-linked genetic disorder show some promise. Especially in girls with the disorder--while it is recessive, trauma or times of high digestive stress, such as starvation or pregnancy, can cause previously unexpressed OCTD to become expressed--liver transplants have been highly effective in preventing later episodes of hyperammonemia. Many also hope that recent work in gene therapy will provide a cure.
Tags: carbamoyl phosphate, urea cycle, Ornithine carbamoyltransferase, also found, amino acid