OTC

Related Reading

Ornithine transcarbamylase (OTC) is one of the five enzymes required for the urea cycle. Human OTC genes are located on the X chromosome, genomic DNA and proteins have been sequenced, and the X-ray three-dimensional structure of the protein has also been published. Ornithine transcarbamylase (OTC) is one of the five enzymes required for the urea cycle. Human OTC genes are located on the X chromosome, genomic DNA and proteins have been sequenced, and the X-ray three-dimensional structure of the protein has also been published. OTC provides a good model for basic scientists to study enzyme proteins that input mitochondria and further assemble into trimers. Clinically, OTC defect caused by OTC gene mutation is a relatively common and very serious genetic metabolic disease in pediatrics, and it is the most common genetic disease that causes urea cycle disorders.

Figure 1. Protein structure of Ornithine transcarbamylase.

Clinical manifestations

Neonatal period: about 1/3 of OTCD, manifested as convulsions, abnormal muscle tone, vomiting, coma, etc. Due to the rapid onset, diagnosis is difficult and the mortality rate is extremely high. Late onset: The individual patients vary greatly, and the onset is more than in infants. Most late-onset patients have no specific symptoms before the first onset, and their mental development is normal. There are also a few patients who develop the disease after adulthood, and even some carriers of the OTC variant gene will not develop the disease for life. In stress conditions such as fever, hunger, infection, and surgery, the increase in muscle protein breakdown may lead to an acute attack of hyperammonemia.

Pharmacological value

Normal value of ornithine carbamoyl transferase: 8～20u/L.

Clinical significance of ornithine carbamoyl transferase:

Decrease: seen in premature babies, ornithine carbaamoyl transferase deficiency, etc.

Elevated: Significantly elevated is seen in patients with acute viral hepatitis, liver cancer, hepatocyte necrosis, acute liver damage caused by drugs or acute pancreatitis, and severe shock. Mild or moderate elevations are seen in liver cirrhosis, gallstones, chronic alcoholism, chronic hepatitis, liver abscess, primary or secondary liver cancer, liver trauma, after various operations, after radiotherapy, acute enteritis, etc.

OTC monomer

Mutations in the OTC gene can lead to insufficient ornithine aminotransferase. Without proper OTC function, ammonia will begin to accumulate in the blood, so it is classified as a urea cycle disorder. The accumulation of ammonia in the blood is called hyperammonemia. Although ammonia is toxic, it is the body's nitrogen source. Therefore, the increased content will lead to an increase in the content of amino acids, glutamic acid and alanine. As the blood urea nitrogen content decreases, the phosphocarbamyl phosphate (CP) content will begin to decrease. This will cause CP to shift to the uridine monophosphate synthesis pathway. Orotic acid is the product of this pathway. Elevated levels of orotic acid in urine can indicate that the patient has a disease related to hyperammonemia.

Treatment

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. Biotin also plays an important role in the functioning of the OTC enzyme and has been shown to reduce ammonia intoxication in animal experiments. Additionally, the use of whole-body therapeutic hypothermia (TH) has been proposed and studied as a treatment. TH is thought to increase the effectiveness of dialysis to extract ammonia from the body.