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 Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

. 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 Vitamins are Organic compound, organic molecules (or a set of closely related molecules called vitamer, vitamers) that are essential to an organism in small quantities for proper metabolism, metabolic function. Nutrient#Essential nutrients, ...

. The compound is synthesized in the body via a mitochondrial 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 a person'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 ...

(to increase their bioavailability), most commonly for lithium orotate.

Synthesis

Dihydroorotate is synthesized to orotic acid by the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

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

Chemistry

Orotic acid is a Bronsted acid and its conjugate base, the orotate anion, is able to bind to metals. Lithium orotate, for example, has been investigated for use in treating

alcoholism Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...

, and complexes of cobalt,

manganese Manganese is a chemical element; it has Symbol (chemistry), symbol Mn and atomic number 25. It is a hard, brittle, silvery metal, often found in minerals in combination with iron. Manganese was first isolated in the 1770s. It is a transition m ...

, nickel, and zinc are known. The pentahydrate nickel orotate coordination complex converts into a polymeric trihydrate upon heating in water at 100 °C. 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 and acidemia. It may be a symptom of an increased

ammonia Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...

load due to a metabolic disorder, such as a urea cycle disorder. 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 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 (TCA) decreasing

adenosine triphosphate Adenosine triphosphate (ATP) is a nucleoside triphosphate that provides energy to drive and support many processes in living cell (biology), cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. Found in all known ...

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

Biochemistry

Orotic acid is a precursor to a RNA base, uracil. The breast milk of smokers has a higher concentration of orotic acid than that of a non smoking

woman A woman is an adult female human. Before adulthood, a female child or Adolescence, adolescent is referred to as a girl. Typically, women are of the female sex and inherit a pair of X chromosomes, one from each parent, and women with functi ...

. It is reasoned that the smoking causes the pyrimidine biosynthesis process in the mother to be altered thus causing the orotic acid concentration to increase. A modified orotic acid (5-fluoroorotic acid) is toxic to yeast. The mutant yeasts which are resistant to 5-fluoroorotic acid require a supply of

uracil Uracil () (nucleoside#List of nucleosides and corresponding nucleobases, symbol U or Ura) is one of the four nucleotide bases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via ...

References

External links

* {{DEFAULTSORT:Orotic Acid Pyrimidinediones Enoic acids