L-Dihydroorotic acid
[CAS# 5988-19-2]

Identification

• Classification: Biochemical >> Nucleic acid drug
• Name: L-Dihydroorotic acid
• Synonyms: L-4,5-dihydroorotic acid; (S)-2,6-Dioxohexahydro-4-pyrimidinecarboxylic acid
• Protein Sequence: X
• Molecular Formula: C₅H₆N₂O₄
• Molecular Weight: 158.11
• CAS Registry Number: 5988-19-2
• EC Number: 624-952-7
• SMILES: C1[C@H](NC(=O)NC1=O)C(=O)O

Properties

• Density: 1.5±0.1 g/cm³, Calc.^*, 1.523
• Melting point: 254-255 $deree$C (dec.)
• Index of Refraction: 1.519, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

Discovory and Applicatios

L-Dihydroorotic acid is a pyrimidine derivative with the chemical formula C5H6N2O4. It is a key intermediate in the biosynthesis of pyrimidine nucleotides, which are essential components of RNA and DNA. The compound has garnered significant interest in both biochemical research and pharmaceutical applications due to its biological importance and potential therapeutic benefits.

The discovery of L-dihydroorotic acid can be traced back to the early 1950s when it was first identified as a product of the de novo synthesis pathway of pyrimidines in organisms. This pathway involves the conversion of simple precursors into uridine and cytidine nucleotides, crucial for various cellular processes. L-Dihydroorotic acid is produced from the reaction of carbamoyl phosphate and aspartate, catalyzed by the enzyme dihydroorotase. Further conversion leads to orotic acid, which is then transformed into uridine monophosphate (UMP). The recognition of L-dihydroorotic acid's role in nucleotide metabolism laid the foundation for subsequent research into its functions and applications.

In terms of applications, L-dihydroorotic acid has been studied for its potential therapeutic effects in various medical conditions. One of the primary areas of interest is its role in cellular energy metabolism. Research has shown that L-dihydroorotic acid can stimulate mitochondrial function and enhance energy production, making it a candidate for the treatment of metabolic disorders and conditions associated with mitochondrial dysfunction. Some studies suggest that it may have neuroprotective properties, which could be beneficial in neurodegenerative diseases.

Moreover, L-dihydroorotic acid has been investigated for its immunomodulatory effects. It has been shown to promote the proliferation of lymphocytes and enhance immune responses, indicating its potential as an adjuvant in vaccine formulations and immunotherapies. These properties have sparked interest in its use as a supplement to support immune health and overall well-being.

Another notable application of L-dihydroorotic acid is in the field of pharmacology. It serves as a precursor in the synthesis of various pharmaceutical compounds, particularly those related to nucleoside and nucleotide analogs. These analogs play crucial roles in antiviral and anticancer therapies, as they can interfere with the synthesis of nucleic acids in pathogens and cancer cells. The ability of L-dihydroorotic acid to participate in the synthesis of these critical drugs highlights its importance in the pharmaceutical industry.

Furthermore, L-dihydroorotic acid has been explored in nutritional studies. It is present in certain food sources, and its supplementation may provide health benefits related to nucleotide metabolism and energy production. Research into its role as a dietary supplement is ongoing, with potential implications for enhancing athletic performance and recovery.

Despite its promising applications, the use of L-dihydroorotic acid must be approached with caution. While it is generally considered safe, excessive intake may lead to metabolic disturbances. As with any compound that affects metabolic pathways, it is essential for individuals to consult healthcare professionals before starting supplementation, especially for those with underlying health conditions or those taking medications.

In summary, L-dihydroorotic acid is a significant compound in the realm of biochemistry, with a notable history of discovery and diverse applications in medicine, pharmacology, and nutrition. Its role in nucleotide synthesis and potential therapeutic benefits continue to make it an important subject of study, underscoring its relevance across multiple scientific disciplines.

References

2023. Beyond genetics: Deciphering the impact of missense variants in CAD deficiency. Journal of Inherited Metabolic Disease, 46(6).
DOI: 10.1002/jimd.12667

2016. Elevated plasma dihydroorotate in Miller syndrome: Biochemical, diagnostic and clinical implications, and treatment with uridine. Molecular Genetics and Metabolism, 119(1-2).
DOI: 10.1016/j.ymgme.2016.06.008

2012. Miller (Genee-Wiedemann) syndrome represents a clinically and biochemically distinct subgroup of postaxial acrofacial dysostosis associated with partial deficiency of DHODH. Human Molecular Genetics, 21(18).
DOI: 10.1093/hmg/dds218