Question

1. The ramifications to human metabolism if the liver lacking the enzyme ornithine transcarbamoylase

Answer 1

Ornithine transcarbamylase (OTC) is the enzyme responsible for catalyzing the production of citrulline by the combination of carbamyl phosphate and ornithine.

Ornithine transcarbamylase deficiency is the most common urea cycle disorder in humans. It is an inherited disorder which causes toxic levels of ammonia to build up in the blood.It is responsible for converting carbamoyl phosphate and ornithine into citrulline. OTC deficiency is inherited in an X-linked recessive manner, meaning males are more commonly affected than females.

In the classic presentation, a male infant appears well initially, but by the second day of life becomes irritable, lethargic, and stops feeding. Infants may have poorly-controlled body temperature and respiratory rates, and may experience seizures. Without urgent intervention, a metabolic encephalopathy develops; this can progress to coma and death within the first week of life.High levels of ammonia cause preferential damage to the brain, leading to devastating consequences.

In individuals with marked hyperammonemia, a urea cycle disorder is usually high on the list of possible causes. While the immediate focus is lowering the patient's ammonia concentrations, identifying the specific cause of increased ammonia levels is key as well.An individual with untreated OTC deficiency will show decreased citrulline and arginine concentrations.

The treatment goal for individuals affected with OTC deficiency is the avoidance of hyperammonemia. This can be accomplished through a strictly controlled low-protein diet, as well as preventive treatment with nitrogen scavenging agents such as sodium benzoate. The goal is to minimize the nitrogen intake while allowing waste nitrogen to be excreted by alternate pathways. Arginine is typically supplemented as well, in an effort to improve the overall function of the urea cycle. If a hyperammonemic episode occurs, the aim of treatment is to reduce the individual's ammonia levels as soon as possible. In extreme cases, this can involve hemodialysis.Gene therapy had been considered a possibility for curative treatment for OTC deficiency.