What is the significance of synthesis of orotic acid?

What is the significance of synthesis of 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.

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.

How does orotic aciduria cause growth retardation?

It is the only known enzyme deficiency of the de novo pyrimidine synthesis pathway. Orotic aciduria is characterized by excessive excretion of orotic acid in urine because of the inability to convert orotic acid to UMP. It causes megaloblastic anemia and may be associated with mental and physical developmental delays.

What are the main cause of raised orotic acid?

It may be a symptom of an increased ammonia load due to a metabolic disorder, such as a urea cycle disorder. In ornithine transcarbamylase deficiency, an X-linked inherited and the most common urea cycle disorder, excess carbamoyl phosphate is converted into orotic acid.

Is orotic acid safe?

Orotic acid has a low acute toxicity. In repeated doses orotic acid induces fatty livers in the rat, but not in other species tested. No data were submitted on reproductive and developmental toxicity and only irrelevant data on genotoxicity.

What is orotic acid used for?

Orotic acid is a drug used to manage uncomplicated liver dysfunction in combination with xanthine.

Is orotic acid harmful?

Orotic acid has a low acute toxicity. In repeated doses orotic acid induces fatty livers in the rat, but not in other species tested.

What is orotic acid good for?

(2) Orotic acid may improve myocardial purine and pyrimidine levels by stimulating hepatic release of uridine into the bloodstream, which in turn augments depleted myocardial pyrimidines and purines (rat heart). (3) Orotic acid improves the tolerance of the recently infarcted heart to global ischemia (rats).

What are the symptoms of orotic aciduria?

The symptoms of the disease include mental retardation, growth retardation, megaloblastic anemia, immunodeficiency, and high levels of orotic acid in the patient’s urine, approximately 500 to 1000 times the normal amount.

Is orotic acid a pyrimidine?

Orotic acid is an intermediate in the biosynthetic pathway of pyrimidines, and this is its main source in the body (Fig. 8) [109,171].

What contains orotic acid?

Orotic acid is a minor dietary constituent (1). Indeed, until it was realized that it could be synthesized by humans, orotic acid was known as vitamin B-13 (2). The richest dietary sources are cow’s milk and other dairy products (3) as well as root vegetables such as carrots and beets (1).

How does the orotic aciduria gene affect the body?

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.

Why is orotic acid not converted to UMP?

The most frequently observed inborn error of pyrimidine nucleotide synthesis is a mutation of the multifunctional protein UMP synthase (UMP synthase deficiency or orotic aciduria). This disorder prevents the conversion of orotic acid to UMP, and thus to other pyrimidines.

How does orotic acid play a role in gene transcription?

In addition to being broken down in the pyrimidine biosynthesis pathway, orotic acid is also believed to improve the metabolism of folic acid and vitamin B12, and may play a role in gene transcription, which is the process by which genetic information is copied from DNA to RNA in order to create a useful product like a specific protein.

What kind of chemical is orotic acid white?

Orotic acid appears as white crystals or crystalline powder. (NTP, 1992) CAMEO Chemicals. Orotic acid is a pyrimidinemonocarboxylic acid that is uracil bearing a carboxy substituent at position C-6. It has a role as a metabolite, an Escherichia coli metabolite and a mouse metabolite. It derives from a uracil.

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