Table of Contents
What is ornithine Carbamoyltransferase deficiency?
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 the function of ornithine transcarbamylase?
The specific role of the ornithine transcarbamylase enzyme is to control the reaction in which two compounds, carbamoyl phosphate and ornithine, form a new compound called citrulline.
Why is glutamine increased in OTC deficiency?
Ammonia also circulates in the body as free ammonia or within glutamine which functions as a temporary “repository” for ammonia. Consequently, in a urea cycle defect not only does free ammonia rise (hyperammonemia) but glutamine is also elevated.
Is ornithine an orotic acid?
Orotic acid is a pyrimidinedione and a carboxylic acid. Historically it was believed to be part of the vitamin B complex and was called vitamin B13, but it is now known that it is not a vitamin….Orotic acid.
| Clinical data | |
|---|---|
| CAS Number | 65-86-1 |
| PubChem CID | 967 |
| IUPHAR/BPS | 4690 |
| DrugBank | DB02262 |
What causes high orotic acid?
Hereditary orotic aciduria is caused by variations in the uridine monophosphate synthetase (UMPS) gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced.
What is the reaction catalyzed by ornithine transcarbamylase Why would a deficiency of this enzyme cause an ammonia buildup?
The ornithine transcarbamylase enzyme starts a specific reaction within the urea cycle. In ornithine transcarbamylase deficiency, as its name suggests, the ornithine transcarbamylase enzyme is damaged or missing. The urea cycle cannot proceed normally, and nitrogen accumulates in the bloodstream in the form of ammonia.
Is ornithine transcarbamylase deficiency autosomal dominant?
Ornithine transcarbamylase deficiency is an X-linked disorder. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes . A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
How is orotic acid formed?
Orotic acid, first discovered in ruminant milk, is an intermediate in the pyrimidine biosynthesis pathway of animal cells. Its synthesis is initiated by the formation of carbamoyl phosphate (CP) in the cytoplasm, with ammonia derived from glutamine.
What causes orotic acid?
In humans and other organisms, orotic acid is synthesized by the enzyme dihydroorotate dehydrogenase which converts dihydroorotate to orotic acid [3]. It has been found that orotic acid improves the metabolism of folic acid and vitamin B12.
Where does orotic acid come from?
Orotic acid is found in milk produced by cows and other commercial dairy products derived from milk. The presence of orotate in mammals is important to the development of the central nervous system [1]. The importance of orotic acid in human metabolism can be witnessed in individuals afflicted with orotic aciduria.
Is OTC deficiency dominant or recessive?
OTC deficiency is an X-linked recessive disorder resulting in severe disease in affected boys. As in CPSI deficiency, boys with complete OTC deficiency rapidly develop high levels of ammonia soon after birth. Patients who recover from their first crisis are at risk for repeated bouts of hyperammonemia.
What is ornithine transcarbamylase (OTC) deficiency?
Ornithine transcarbamylase (OTC) deficiencyis a genetic disease that causes too much ammonia to accumulate in the blood (hyperammonemia). Ammonia is toxic when levels are too high and especially affects the nervous system.
What is the functional enzyme for ornithine transcarbamylase?
Genetics. The functional enzyme consists of three identical subunits. OTC is the last enzyme in the proximal portion of the urea cycle, which consists of the reactions that take place in the mitochondria. The substrates of the reaction catalyzed by ornithine transcarbamylase are ornithine and carbamyl phosphate, while the product is citrulline.
What causes increased orotic acid in ornithine deficiency?
The increased orotic acid concentrations result from the buildup of carbamoyl phosphate. This biochemical phenotype (increased ammonia, low citrulline and increased orotic acid) is classic for OTC deficiency, but can also be seen in neonatal presentations of ornithine aminotransferase deficiency.
What is the classic biochemical phenotype of ornithine aminotransferase deficiency?
This biochemical phenotype (increased ammonia, low citrulline and increased orotic acid) is classic for OTC deficiency, but can also be seen in neonatal presentations of ornithine aminotransferase deficiency. Only severely affected males consistently demonstrate this classic biochemical phenotype. Heterozygous females can be difficult to diagnose.