What causes carbamoyl phosphate synthetase deficiency?

CPSID is inherited as an autosomal recessive genetic disorder and is caused by mutations in the CPSI gene. Mutations in the CPSI gene result in production of an abnormal carbamoyl phosphate synthetase enzyme.

What does carbamoyl phosphate synthetase do?

The specific role of the carbamoyl phosphate synthetase I enzyme is to control the first step of the urea cycle, a reaction in which excess nitrogen compounds are incorporated into the cycle to be processed. Carbamoyl phosphate synthetase I deficiency belongs to a class of genetic diseases called urea cycle disorders.

What is the role of carbamoyl phosphate synthetase in urea cycle?

Carbamoyl phosphate synthetase I is a ligase enzyme located in the mitochondria involved in the production of urea. Carbamoyl phosphate synthetase I (CPS1 or CPSI) transfers an ammonia molecule to a molecule of bicarbonate that has been phosphorylated by a molecule of ATP.

What two metabolic produces carbamoyl phosphate?

CPS catalyzes the synthesis of carbamoyl phosphate (CP) from ATP and bicarbonate, using either glutamine or ammonia as a nitrogen source depending on the type of the enzyme.

What is OTC disease?

Ornithine transcarbamylase (OTC) deficiency is a rare X-linked genetic disorder characterized by complete or partial lack of the enzyme ornithine transcarbamylase (OTC). OTC is one of six enzymes that play a role in the break down and removal of nitrogen the body, a process known as the urea cycle.

What is CPS in a baby?

Carbamoyl phosphate synthetase I deficiency (CPS) is an inherited condition in which the body is unable to process and remove the waste, ammonia. CPS is considered an amino acid condition because ammonia is produced when the body breaks down proteins in food into their basic building blocks (amino acids).

Where is carbamoyl phosphate synthetase found?

mitochondria
Carbamoyl phosphate synthetase I (CPS I) is located in the inner membrane of mitochondria in the liver and, to a lesser extent, in the kidneys and small intestine. It supplies carbamoyl phosphate for the urea cycle. CPS I is specific for ammonia as nitrogen donor and requires N-acetylglutamate as activator.

What is the reaction mechanism for carbamoyl phosphate synthetase II?

Carbamoyl phosphate synthase II step—Carbamoyl phosphate synthetase II catalyzes the reaction of bicarbonate and ammonia from glutamine in the cytoplasm to produce carbamoyl phosphate. This enzyme is different from CPS I involved in urea synthesis.

What is OTD disorder?

Collapse Section. Ornithine transcarbamylase deficiency is an inherited disorder that causes ammonia to accumulate in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia.

How is carbamoyl phosphate regulated?

This enzyme is part of a multifunctional enzyme complex (CAD) and is the control point for pyrimidine synthesis. Its activity is regulated by positive feedback from 5-phosphoribosyl-1-pyrophosphate and negative feedback by uridine triphosphate. Unlike the mitochondrial enzyme CPSI, CPSII is not activated by NAG [50].

Can OTC deficiency be cured?

Genetic counseling is recommended for individuals with OTC deficiency and their families. In some cases, liver transplantation, either cadaveric or from a living donor, may be an appropriate treatment option. Liver transplantation can cure the hyperammonemia in OTC deficiency.

Is hyperammonemia genetic?

In the genetic forms of hyperammonemia, men and women are affected equally because almost all types are autosomal recessive traits. The only exception to equal sex distribution is X-linked ornithine transcarbamylase (OTC) deficiency, the most common of the urea cycle disorders.

What are 5 protective factors?

Understanding the Five Protective Factors

• Parental Resilience.
• Social Connections.
• Knowledge of Parenting & Child Development.
• Concrete Support in Times of Need.
• Social and Emotional Competence of Children.

What is the cofactor of carbamoyl phosphate synthetase?

Ammonia is converted to carbamoyl phosphate for entry in the cycle by carbamoyl phosphate synthetase I (CPS-I). This reaction utilizes N-acetyl glutamate as cofactor formed by the enzyme N-acetyl glutamate synthetase (NAGS) from acetyl-coA and glutamate.

What is the difference between carbamoyl phosphate synthetase 1 and 2?

CPS I is the most plentiful single protein in hepatic mitochondria, accounting for about 20% of the matrix protein. CPS II is exclusively cytosolic and is an important enzyme in de novo synthesis of pyrimidine nucleotides.

Is there a cure for OTC?

Is OTC deficiency fatal?

Our case, similar to the previously few reported cases of OTC deficiency, presented with a rapidly worsening coma that, unfortunately, can be potentially fatal [9]. Indeed, death is an usual outcome of the disease in its mild forms.

Does a liver transplant cure OTC deficiency?

In conclusion, for patients with OTC deficiency who have hyperammonemic encephalopathy, orthotopic liver transplantation is an appropriate treatment.

How common is OTC deficiency?

The estimated frequency of OTC deficiency is 1/50,000 – 80,000. The estimated frequency of urea cycle disorders collectively is 1/35,000.