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 into the bloodstream after both intraperitoneal and subcutaneous injection, but was not completely absorbed from the peritoneum until 20 minutes after injection. Subcutaneous injection should be an acceptable alternative to intraperitoneal injection, although the incorporation of orotic acid into the hepatic acid-soluble and RNA components is slightly delayed after subcutaneous injection. Metabolism/Metabolites …This study aimed to investigate whether there are differences in the metabolism of orotic acid in the intestine and liver, thereby explaining its lack of effect on intestinal lipoprotein secretion. High levels of the multienzyme complex (complex U) were detected in the livers of rats, mice, and rabbits; the levels of the multienzyme complex were much lower in the intestinal mucosa of the latter two animals, while its activity was undetectable in the rat intestine. In fact, radiolabeled aspartic acid and orotic acid were not incorporated into the RNA of intestinal cells. The rat intestine lacks orotic acid phosphoribosyltransferase and orotic acid 5'-phosphate decarboxylase activities, resulting in impaired orotic acid metabolism. This may explain why, unlike the liver, the intestine is protected from the effects of orotic acid supplementation diet on nucleotide metabolism disorders and lipoprotein secretion abnormalities.

Interactions
In rats treated with phenobarbital for 3 days and simultaneously fed a semi-synthetic diet containing 1.0% orotic acid, the increases in hepatic microsomal phosphatidylcholine, phosphatidylethanolamine, total RNA, total protein, and cytochrome P-450 were significantly greater than in rats treated with the same phenobarbital alone but without orotic acid. This was primarily attributed to dietary orotic acid stimulating hepatic phosphatidylcholine synthesis. In the absence of phenobarbital, orotic acid led to an increase in the components of the smooth endoplasmic reticulum in the liver but not an increase in cytochrome P-450. Orotic acid also reduced the activity of microsomal phosphatidylethanolamine N-methyltransferase, which may contribute to the increase in microsomal phosphatidylethanolamine levels. It is hypothesized that phospholipid availability is a limiting factor for hepatic response to phenobarbital. When more phospholipids are available to provide the structural framework for endoplasmic reticulum biosynthesis, all hepatic effects of phenobarbital, including the induction of cytochrome P-450, are enhanced.

---

Non-human toxicity values
Mice intravenous LD50: 770 mg/kg
Mice intraperitoneal LD50: 841 mg/kg
Mice oral LD50: 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 is a white crystalline or crystalline powder. (NTP, 1992)
Orotic acid is a pyrimidine monocarboxylic acid, a compound of uracil with a carboxyl substituent at the C-6 position. It is a metabolite, and also a metabolite of E. coli and mice. Its function is related to uracil. It is the conjugate acid of orotic acid.
Orotic acid is a metabolite found or produced in E. coli (K12 strain, MG1655 strain).
Orotic acid has also been reported in water fleas, fruit flies, and some other organisms with relevant data.
Orotic acid is a minor dietary component. In fact, before it was discovered that the human body could synthesize orotic acid, it was known as vitamin B13. The richest dietary sources of orotic acid are milk and other dairy products, as well as root vegetables such as carrots and beets. Dietary intake may affect the basal excretion rate of orotic acid in urine, as fasting reduces excretion by about 50%. However, it is now clear that most orotic acid in urine is synthesized in the body; it is an intermediate product in the pyrimidine nucleotide synthesis pathway. Orotic acid is converted to UMP by UMP synthase, a multifunctional protein with both orotic acid phosphoribosyltransferase and orotic acid decarboxylase activities. The most common congenital defect in pyrimidine nucleotide synthesis is a mutation in the multifunctional protein UMP synthase. This defect prevents the conversion of orotic acid to UMP, and consequently, to other pyrimidines. As a result, plasma orotic acid concentrations are elevated, and urinary orotic acid content also increases. In fact, individuals carrying the UMP synthase mutation have significantly higher urinary orotic acid levels, to the point that orotic acid crystals form in the urine. Homozygous individuals can achieve orotic acid concentrations in urine at millimoles per millimole of creatinine. In contrast, unaffected individuals have orotic acid levels in urine of approximately 1 μmol/mmol creatinine (A3380). Orotic acid is a metabolite found or produced in Saccharomyces cerevisiae. It is an intermediate in pyrimidine synthesis and plays a role in the chemical conversion between dihydrofolate and tetrahydrofolate. See also: fatty acids, tall oil, ethoxylation (note moved to)... See more...

---

Therapeutic Uses
Uric Acid Excretion Promotion
This study investigated the potential therapeutic effects of orotic acid (OA) and magnesium orotic acid (MgO) on the development of myocardial degeneration and congestive heart failure in UM-X7.1 strain cardiomyopathy (CM) hamsters. Two main age groups (Group I, < 30 days; Group II, > 180 days) were used, with experiments lasting 30 and 50 days, respectively; orotic acid (10%) was added to Purina laboratory feed for free access. Macroscopic and microscopic assessments of pathological changes, combined with electrocardiographic recordings, showed that magnesium oxide (MgO) treatment significantly reduced the severity of myocardial damage, particularly calcification. Electrocardiogram recordings clearly showed significant shortening of the QTc and PR intervals, thereby stabilizing the electrophysiology of the failing heart and significantly delaying the onset of systemic congestive changes. In animals treated with orotic acid (OA), the effect on preventing cardiac lesions was not significant, but both formulations were equally effective in prolonging the survival of hamsters with myocardial infarction (CM). Three studies were conducted: (1) In unoperated rats, changes in the concentration of pyrimidine compounds in tissues and plasma were detected after administration of 100 mg/kg orotic acid. (2) In experimental myocardial infarction, rats were administered orotic acid (30 mg/kg/d) for two consecutive days, and the concentration of pyrimidine compounds in tissues and plasma was detected; the heart was removed and perfused in an isolated working rat heart model (37°C) with 30 minutes of global ischemia to assess cardiac function recovery. The AN content in non-infarcted myocardium was assessed before and after ischemia. Isolated hearts were perfused with hypoxia for 30 minutes, and the effect of adding 17 μM uridine to the perfusion fluid was investigated. Study 1 showed that OA administration led to increased hepatic uridine and cytidine levels, followed by increases in plasma uridine and cytidine levels (cytidine increased by 55%, P < 0.001; uridine increased by 124%, P = 0.011). Myocardial uracil nucleotides transiently increased after 4 hours (21%, P < 0.01). In infarcted hearts, myocardial uracil or cytidine nucleotides and total RNA did not change significantly 2 days after OA administration. Infarction significantly reduced functional recovery after global cardiac ischemia (62% of pre-ischemic levels in the sham-operated group; 26% of pre-ischemic levels in the infarcted group; P < 0.05). OA treatment improved pre-ischemic functional recovery in infarcted hearts by 133% (P < 0.05), but this phenomenon was not observed in the sham-operated group. In surviving myocardium of infarcted hearts, pre-ischemic ATP and total adenine nucleotide (TAN) levels were decreased (ATP from 21.7 ± 0.8 μmol/g dry weight to 14.7 ± 0.7 μmol/g dry weight, P < 0.001; TAN from 30.3 ± 0.8 μmol/g dry weight to 22.4 ± 1.1 μmol/g dry weight, P < 0.001). OA treatment halted these decreases. Study 3 showed that uridine improved myocardial ATP and TAN levels in hypoxic hearts and reduced purine loss. Elevated AN levels were accompanied by evidence of enhanced anaerobic 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.

---

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