Orotic acid is a
pyrimidinedione 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. Carboxylic ...
. Historically, it was believed to be part of the
vitamin B
B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds that often coexist ...
complex and was called vitamin B
13, 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 Nutrient#Essential nutrients, essential micronutrient that an organism needs in small quantities for the proper functioning of its ...
.
The compound is synthesized in the body via a
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
l enzyme,
dihydroorotate dehydrogenase 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 (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients either extr ...
(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%. H ...
), most commonly for
lithium orotate
Lithium orotate (C5H3LiN2O4) is a salt of orotic acid and lithium. It is available as the monohydrate, LiC5H3N2O4·H2O. In this compound, lithium is non-covalently bound to an orotate ion, rather than to a carbonate or other ion, and like other ...
.
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. A ...
dihydroorotate dehydrogenase, where it later combines with
phosphoribosyl pyrophosphate
Phosphoribosyl pyrophosphate (PRPP) is a pentose phosphate. It is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, as well as in pyrimidine nucleotide formation. Hence it is a building block for DN ...
(PRPP) to form
orotidine-5'-monophosphate (OMP). A distinguishing characteristic of
pyrimidine synthesis
Pyrimidine biosynthesis occurs both in the body and through organic synthesis.
''De novo'' biosynthesis of pyrimidine
''De Novo'' biosynthesis of a pyrimidine is catalyzed by three gene products CAD, DHODH and UMPS. The first three enzymes of ...
is that the pyrimidine ring is fully synthesized before being attached to the
ribose sugar, 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 to ...
. 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 Bipyridines also known as bipyridyls, dipyridyls, and dipyridines, are a family of chemical compounds with the formula (C5H4N)2, consisting of two pyridyl (C5H4N) rings. Pyridine is an aromatic nitrogen-containing heterocycle. Bipyridines are of si ...
present other solids can be obtained.
Pathology
A buildup of orotic acid can lead to
orotic aciduria 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 was ...
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 the ...
, 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 important r ...
.
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, re ...
, 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 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 of ...
(ATP) production.
Orotic aciduria is a cause of megaloblastic anaemia.
See also
*
Magnesium orotate
*
Pyrimidine biosynthesis
References
Further reading
*
External links
*
{{DEFAULTSORT:Orotic Acid
Pyrimidinediones
Enoic acids