Orotic acid is a

pyrimidinedione Pyrimidinediones are a class of chemical compounds characterized by a pyrimidine ring substituted with two carbonyl groups. Examples include naturally occurring metabolites: drugs: * Fluorouracil * Idoxuridine * Primidone * Trifluridine and p ...

and a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyli ...

. 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 A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrie ...

. The compound is synthesized in the body via a

mitochondria A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...

l enzyme,

dihydroorotate dehydrogenase Dihydroorotate dehydrogenase (DHODH) is an enzyme that in humans is encoded by the ''DHODH'' gene on chromosome 16. The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate t ...

or a cytoplasmic enzyme of pyrimidine synthesis pathway. It is sometimes used as a mineral carrier in some

dietary supplements A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

(to increase their

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

), most commonly for lithium orotate.

Synthesis

Dihydroorotate is synthesized to orotic acid by the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

dihydroorotate dehydrogenase, where it later combines with phosphoribosyl pyrophosphate (PRPP) to form orotidine-5'-monophosphate (OMP). A distinguishing characteristic of pyrimidine synthesis is that the pyrimidine ring is fully synthesized before being attached to the

ribose sugar Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this comp ...

, whereas purine synthesis happens by building the base directly on the sugar.

Chemistry

Orotic acid is a Bronsted acid and the anion (orotate) is able bind to metals. For example it forms a pentahydrate complex with

nickel Nickel is a chemical element with symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive but large pieces are slow t ...

. On heating in water at 100 oC the pentahydrate is converted into polymeric trihydrate.M.J.Plater, M.R.St.J.Foreman, J.M.S.Skakle, R.A.Howie CCDC 189770: Experimental Crystal Structure Determination, 2002, DOI: 10.5517/cc6cgmm Crystals of the trihydrate can be obtained by hydrothermal treatment of nickel(II) acetate and orotic acid, when the reactions are run with bidentate nitrogen ligands such as 2,2'- bipyridine present other solids can be obtained.

Pathology

A buildup of orotic acid can lead to

orotic aciduria Orotic aciduria (AKA hereditary orotic aciduria) is a disease caused by an enzyme deficiency resulting in a decreased ability to synthesize pyrimidines. It was the first described enzyme deficiency of the ''de novo'' pyrimidine synthesis pathway. ...

and acidemia. It may be a symptom of an increased

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...

load due to a

metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter t ...

, such as a

urea cycle disorder Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an importan ...

. In

ornithine transcarbamylase deficiency Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder is the final enzyme in the proximal portion of the urea cycle, r ...

, an X-linked inherited and the most common urea cycle disorder, excess carbamoyl phosphate is converted into orotic acid. This leads to an increased serum ammonia level, increased serum and urinary orotic acid levels and a decreased serum

blood urea nitrogen Blood urea nitrogen (BUN) is a medical test that measures the amount of urea nitrogen found in blood. The liver produces urea in the urea cycle as a waste product of the digestion of protein. Normal human adult blood should contain 6 to 20 mg/dL ...

level. This also leads to an increased urinary orotic acid excretion, because the orotic acid is not being properly utilized and must be eliminated. The hyperammonemia depletes alpha-ketoglutarate leading to the inhibition of the

tricarboxylic acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

(TCA) decreasing

adenosine triphosphate Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms ...

(ATP) production. Orotic aciduria is a cause of megaloblastic anaemia.

References

External links

* {{DEFAULTSORT:Orotic Acid Pyrimidinediones Enoic acids

Synthesis

Chemistry

Pathology

See also

References

Further reading

External links