Milk and dairy products include orotic acid, which is transformed into uridine and used in the pyrimidine salvage pathway, mainly in the kidneys, liver, and red blood cells [2].

Ornithine transcarbamylase deficiency (OTCD) is one of the urea cycle diseases (UCD) that can be measured with orotic acid [2]. Orotic acid (1.0% in the diet; taken orally for 3–10 days) reduces the purine/pyrimidine ratio of hepatic acid-soluble nucleotides on day 3 and causes the onset of fatty liver disease on day 7 [3].

Absorption, Distribution and Excretion
[14C]Orotic acid was rapidly distributed in blood after both i.p. and s.c. injection but was not completely absorbed from the peritoneal cavity until 20 min after injection. S.c. injection should be an acceptable alternative to i.p. injection although the incorporation into the liver acid soluble- and RNA-fractions was somewhat delayed after the s.c. injection.

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Metabolism / Metabolites
... The aim of this work was to investigate whether orotate is differently metabolized in gut and in liver thus explaining the lack of effect on the intestinal lipoproteins secretion. Multienzyme complex (complex U) was found in appreciable amounts in rat, mouse and rabbit livers; the intestinal mucosa of the two last species contains a much lower level of multienzyme complex whereas in rat intestine its activity cannot be detected. Indeed, radioactive aspartate and orotate were not incorporated into intestinal cells RNA. The absence of orotate metabolisation by lack of orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase activity in rat intestine would explain why this organ, in contrast to the liver, is protected against disturbances of nucleotide metabolism and lipoproteins secretion induced by orotic-acid-supplemented diets.

Interactions
In rats treated with phenobarbital for 3 days and simultaneously fed a semisynthetic diet containing 1.0% orotic acid, the extent of the increases in liver microsomal phosphatidylcholine, phosphatidylethanolamine, total RNA, total protein, and cytochrome P-450 were significantly greater than they were in rats treated identically with phenobarbital but without dietary orotic acid. This is attributed primarily to the stimulation of hepatic phosphatidylcholine synthesis by dietary orotic acid. In the absence of phenobarbital, orotic acid was shown to cause some increase in liver smooth endoplasmic reticulum components, but not cytochrome P-450. Orotic acid also decreased the activity of microsomal phosphatidylethanolamine N-methyltransferase, which may have contributed to the increase in the microsomal content of phosphatidylethanolamine. The hypothesis is advanced that phospholipid availability is a limiting factor in the hepatic response to phenobarbital. When more phospholipid is available to provide the structural framework for biogenesis of endoplasmic reticulum, all of the hepatic actions of phenobarbital, including induction of cytochrome P-450, are amplified.

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Non-Human Toxicity Values
LD50 Mouse iv 770 mg/kg
LD50 Mouse ip 841 mg/kg
LD50 Mouse oral 2 g/kg

[1]. Orotate (orotic acid): An essential and versatile molecule. Nucleosides Nucleotides Nucleic Acids.

[2]. The role of orotic acid measurement in routine newborn screening for urea cycle disorders. J Inherit Metab Dis. 2020 Nov 15.

[3]. Orotic acid-induced metabolic changes in the rat. J Nutr. 1980 Apr;110(4):816-21.

Orotic acid appears as white crystals or crystalline powder. (NTP, 1992)
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 is functionally related to a uracil. It is a conjugate acid of an orotate.
Orotic acid is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
Orotic acid has been reported in Daphnia pulex, Drosophila melanogaster, and other organisms with data available.
Orotic acid is a minor dietary constituent. Indeed, until it was realized that it could be synthesized by humans, orotic acid was known as vitamin B-13. The richest dietary sources are cow's milk and other dairy products as well as root vegetables such as carrots and beets. Dietary intake probably contributes to a basal rate of orotic acid excretion in urine because fasting decreases excretion by ~50%. However, it is now apparent that most urinary orotic acid is synthesized in the body, where it arises as an intermediate in the pathway for the synthesis of pyrimidine nucleotides. Orotic acid is converted to UMP by UMP synthase, a multifunctional protein with both orotate phosphoribosyltransferase and orotidylate decarboxylase activity. The most frequently observed inborn error of pyrimidine nucleotide synthesis is a mutation of the multifunctional protein UMP synthase. This disorder prevents the conversion of orotic acid to UMP and thus to other pyrimidines. As a result, plasma orotic acid accumulates to high concentrations, and increased quantities appear in the urine. Indeed, urinary orotic acid is so markedly increased in individuals harboring a mutation in UMP synthase that orotic acid crystals can form in the urine. The urinary concentration of orotic acid in homozygotes can be of the order of millimoles per millimole creatinine. By comparison, the urinary level in unaffected individuals is ~ 1 umol/mmol creatinine. (A3380).
Orotic acid is a metabolite found in or produced by Saccharomyces cerevisiae.
An intermediate product in PYRIMIDINE synthesis which plays a role in chemical conversions between DIHYDROFOLATE and TETRAHYDROFOLATE.
See also: Fatty acids, tall-oil, ethoxylated (annotation moved to) ... View More ...

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Therapeutic Uses
Uricosuric
This study deals with the potential therapeutic effect of orotic acid (OA) and Mg Orotate (MgO) on myocardial degeneration and the development of congestive heart failure in cardiomyopathic (CM) hamsters of the UM-X7.1 line. Two major age groups (group I, < 30 days and group II, > 180 days old) were used in these experiments, which lasted 30 and 50 days, respectively; the orotic salts were incorporated (10%) into Purina Lab Chow given ad libitum. Macroscopic and microscopic assessment of pathologic changes together with ECG recordings revealed that MgO treatment significantly reduces myocardial damage, especially the severity of calcific changes. ECG recordings clearly demonstrated a significant shortening of QTc and PR intervals, resulting in partial electrical stabilization of failing hearts, with a significant delay in systemic congestive changes. The prevention of heart lesions was less evident in animals receiving OA, but both preparations proved to be equally efficient in prolonging survival of the CM hamsters.
... Three studies were performed: (1) The time course of changes in tissue and plasma concentrations of pyrimidine compounds was examined in unoperated rats after the administration of 100 mg/kg OA. (2) Rats were given OA (30 mg/kg/d) for 2 days after experimental infarction, and tissue and plasma pyrimidine concentrations were examined; the hearts were removed for perfusion in the isolated working rat heart model (37 degrees C), subjected to 30 minutes of global ischemia, and recovery of function was assessed. AN content was assessed in the noninfarcted myocardium before and after ischemia. Isolated hearts were subjected to 30 minutes of hypoxic perfusion and the effect of adding 17 microM uridine to the perfusate was examined. Study 1 showed that OA administration produced an increase in hepatic uridine and cytidine, followed by increased plasma uridine and cytidine (cytidine, +55%, P < 0.001; uridine, +124%, P = 0.011). Myocardial uracil nucleotides increased temporarily after 4 hours (+21%, P < 0.01). In infarcted hearts after 2 days of OA administration, there were no significant changes in myocardial uracil or cytosine nucleotides or total RNA. Infarction significantly reduced functional recovery after global ischemia (sham = 62%; infarct = 26% of preischemic level; P < 0.05). OA improved the recovery of preischemic function by 133% (P < 0.05) in infarcted, but not sham-operated, hearts. Preischemic ATP and total adenine nucleotides (TAN) were decreased in the surviving myocardium of infarcted hearts (ATP reduced from 21.7 +/- 0.8 to 14.7 +/- 0.7 mumol/g dry wt, P < 0.001; TAN decreased from 30.3 +/- 0.8 to 22.4 +/- 1.1 mumol/g dry wt, P < 0.001). OA treatment prevented these reductions. Study 3 showed that uridine improved myocardial ATP and TAN levels, and decreased purine loss in hypoxic hearts. The increased AN levels were accompanied by evidence of enhancement of anerobic glycolysis.

C5H4N2O4

156.0963

156.017

65-86-1

Orotic acid potassium;24598-73-0;Orotic acid zinc;68399-76-8;Orotic acid-13C,15N2 monohydrate;1346602-15-0

967

White to off-white solid powder

1.8±0.1 g/cm3

656.9±65.0 °C at 760 mmHg

>300°C

351.1±34.3 °C

0.0±2.1 mmHg at 25°C

1.705

-1.4

3

4

1

11

268

0

PXQPEWDEAKTCGB-UHFFFAOYSA-N

InChI=1S/C5H4N2O4/c8-3-1-2(4(9)10)6-5(11)7-3/h1H,(H,9,10)(H2,6,7,8,11)

2,4-dioxo-1H-pyrimidine-6-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~55 mg/mL (~352.34 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.75 mg/mL (17.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)