Quinolinic acid
[CAS# 89-00-9]

Identification

• Classification: Organic raw materials >> Organometallic compound >> Organic zinc
• Name: Quinolinic acid
• Synonyms: 2,3-Pyridinedicarboxylic acid; Pyridine-2,3-dicarboxylic acid
• Molecular Formula: C₇H₅NO₄
• Molecular Weight: 167.12
• CAS Registry Number: 89-00-9
• EC Number: 201-874-8
• SMILES: C1=CC(=C(N=C1)C(=O)O)C(=O)O

Properties

• Density: 1.6±0.1 g/cm³, Calc.^*
• Melting point: 188-190 °C (decomp.) (Expl.)
• Index of Refraction: 1.628, Calc.^*
• Boiling Point: 425.0±30.0 °C (760 mmHg), Calc.^*
• Flash Point: 210.9±24.6 °C, Calc.^*
• Water solubility: 0.55 g/100 mL

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Risk Statements: H302-H315-H318-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P317-P319-P321-P330-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
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	3	H311
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

Quinolinic acid is a metabolite of the amino acid tryptophan, produced in the kynurenine pathway, which is an important biochemical route that contributes to the regulation of various physiological processes. Quinolinic acid is recognized for its neuroactive properties, and its role in the central nervous system has been widely studied, particularly in relation to neurological and psychiatric conditions.

The discovery of quinolinic acid dates back to the early 20th century when researchers were exploring the biochemical pathways involving tryptophan metabolism. The compound was identified as one of the metabolites produced during the breakdown of tryptophan, a precursor to serotonin, through the kynurenine pathway. Quinolinic acid, like many metabolites in this pathway, is involved in the biosynthesis of nicotinic acid (niacin), which is essential for various cellular functions.

Quinolinic acid’s most notable function is its role as an agonist at the NMDA (N-Methyl-D-Aspartate) receptor, a type of glutamate receptor that is critical for synaptic plasticity, learning, and memory. The compound is also a precursor in the synthesis of NAD+ (nicotinamide adenine dinucleotide), a vital coenzyme involved in energy metabolism and cellular redox reactions. These properties make quinolinic acid an important molecule in both the central nervous system and metabolic pathways.

One of the primary applications of quinolinic acid is in neurobiology research. Due to its ability to activate NMDA receptors, quinolinic acid has been used experimentally to induce neurodegeneration in animal models, making it a valuable tool in studying diseases such as Alzheimer's disease, Parkinson’s disease, and Huntington’s disease. The compound is used to investigate excitotoxicity, a process in which excessive activation of NMDA receptors leads to neuronal injury and death, a phenomenon implicated in various neurodegenerative conditions.

Moreover, quinolinic acid has been studied for its involvement in neuroinflammatory processes. Elevated levels of quinolinic acid have been associated with a number of neurological and psychiatric disorders, including schizophrenia, depression, and autoimmune diseases. In particular, increased quinolinic acid levels have been observed in the cerebrospinal fluid of patients with these conditions, suggesting a potential role in the pathophysiology of these diseases. As a result, quinolinic acid has been investigated as a biomarker for certain neuropsychiatric disorders and a target for therapeutic intervention.

In addition to its role in neurobiology, quinolinic acid has been explored for its involvement in immune system function. The kynurenine pathway, which produces quinolinic acid, is tightly linked to immune responses. The metabolism of tryptophan through this pathway influences the activation of T cells and other immune cells, and altered levels of quinolinic acid can affect immune modulation. This has led to investigations into the potential use of quinolinic acid as a marker for immune system activity, particularly in autoimmune and inflammatory diseases.

While quinolinic acid has several established roles in health and disease, its presence in the body must be tightly regulated. Dysregulation of the kynurenine pathway and the accumulation of quinolinic acid can lead to excitotoxicity and contribute to the development of neurodegenerative and psychiatric conditions. Consequently, quinolinic acid has been studied as a potential therapeutic target for drug development. Researchers have sought to identify inhibitors of quinolinic acid synthesis or NMDA receptor antagonists as potential treatments for conditions where quinolinic acid is implicated.

In summary, quinolinic acid is a key metabolic product of the tryptophan breakdown pathway, with important roles in neurotransmission, immune modulation, and cellular metabolism. Its discovery has advanced the understanding of various neurological and psychiatric conditions, where its effects on NMDA receptor activation and neuroinflammation play significant roles. Continued research into quinolinic acid’s functions and its potential therapeutic applications remains a critical area of investigation in the fields of neurobiology and immunology.

References

1994. Kynurenine and probenecid prevent quinolinic acid-induced neurotoxicity in rat corpus striatum. Proceedings of the Western Pharmacology Society, 37.

1998. Chronic exposure of human neurons to quinolinic acid results in neuronal changes consistent with AIDS dementia complex. AIDS (London, England), 12(4).
DOI: 10.1097/00002030-199804000-00003

2000. A caspase-3-like protease is involved in NF-kappaB activation induced by stimulation of N-methyl-D-aspartate receptors in rat striatum. Brain Research. Molecular Brain Research, 82(1-2).
DOI: 10.1016/s0169-328x(00)00147-9