Kynurenic acid
Encyclopedia
Kynurenic acid is a product of the normal metabolism of amino acid L-tryptophan
. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant
, most likely through acting as an antagonist at excitatory amino acid receptors. Because of this activity, it may influence important neurophysiologic and neuropathologic processes. As a result, kynurenic acid has been considered for use in therapy in certain neurobiological disorders. Conversely, increased levels of kynurenic acid have also been linked to certain pathological conditions.
Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig
in dog urine, which it was apparently named after.
It is formed from L-kynurenine
in a reaction catalyzed by the enzyme kynurenine—oxoglutarate transaminase.
Kynurenic acid (KYNA) is a product of the normal metabolism of amino acid L-tryptophan
. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant
, most likely through acting as an antagonist at excitatory amino acid receptors. Because of this activity, it may influence important neurophysiologic and neuropathologic processes. As a result, kynurenic acid has been considered for use in therapy in certain neurobiological disorders. Conversely, increased levels of kynurenic acid have also been linked to certain pathological conditions.
Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig
in dog urine, which it was apparently named after.
It is formed from L-kynurenine
in a reaction catalyzed by the enzyme kynurenine—oxoglutarate transaminase.
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
, most likely through acting as an antagonist at excitatory amino acid receptors. Because of this activity, it may influence important neurophysiologic and neuropathologic processes. As a result, kynurenic acid has been considered for use in therapy in certain neurobiological disorders. Conversely, increased levels of kynurenic acid have also been linked to certain pathological conditions.
Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig
Justus von Liebig
Justus von Liebig was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the...
in dog urine, which it was apparently named after.
It is formed from L-kynurenine
Kynurenine
L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.Kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid...
in a reaction catalyzed by the enzyme kynurenine—oxoglutarate transaminase.
Mechanism of action
KYNA has been found to act on three receptors:- As a noncompetitive antagonist at the glycine site of the NMDA receptorNMDA receptorThe NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
. - As an antagonist of the α7 nicotinic acetylcholine receptorAlpha-7 nicotinic receptorThe alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor, consisting entirely of α7 subunits....
. This action has been recently disputed and if true is contrary to another tryptophan metabolite, 5-hydroxyindoleacetic acid5-Hydroxyindoleacetic acid5-Hydroxyindoleacetic acid is the main metabolite of serotonin in the human body. In chemical analysis of urine samples, 5-HIAA is used to determine the body's levels of serotonin.- Clinical significance :...
.
Kynurenic acid (KYNA) is a product of the normal metabolism of amino acid L-tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
, most likely through acting as an antagonist at excitatory amino acid receptors. Because of this activity, it may influence important neurophysiologic and neuropathologic processes. As a result, kynurenic acid has been considered for use in therapy in certain neurobiological disorders. Conversely, increased levels of kynurenic acid have also been linked to certain pathological conditions.
Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig
Justus von Liebig
Justus von Liebig was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the...
in dog urine, which it was apparently named after.
It is formed from L-kynurenine
Kynurenine
L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.Kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid...
in a reaction catalyzed by the enzyme kynurenine—oxoglutarate transaminase.
Mechanism of action
KYNA has been found to act on three receptors:- As a noncompetitive antagonist at the glycine site of the NMDA receptorNMDA receptorThe NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
. - As an antagonist of the α7 nicotinic acetylcholine receptorAlpha-7 nicotinic receptorThe alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor, consisting entirely of α7 subunits....
. This action has been recently disputed and if true is contrary to another tryptophan metabolite, 5-hydroxyindoleacetic acid5-Hydroxyindoleacetic acid5-Hydroxyindoleacetic acid is the main metabolite of serotonin in the human body. In chemical analysis of urine samples, 5-HIAA is used to determine the body's levels of serotonin.- Clinical significance :...
.
Kynurenic acid (KYNA) is a product of the normal metabolism of amino acid L-tryptophanTryptophanTryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsantAnticonvulsantThe anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
, most likely through acting as an antagonist at excitatory amino acid receptors. Because of this activity, it may influence important neurophysiologic and neuropathologic processes. As a result, kynurenic acid has been considered for use in therapy in certain neurobiological disorders. Conversely, increased levels of kynurenic acid have also been linked to certain pathological conditions.
Kynurenic acid was discovered in 1853 by the German chemist Justus von LiebigJustus von LiebigJustus von Liebig was a German chemist who made major contributions to agricultural and biological chemistry, and worked on the organization of organic chemistry. As a professor, he devised the modern laboratory-oriented teaching method, and for such innovations, he is regarded as one of the...
in dog urine, which it was apparently named after.
It is formed from L-kynurenineKynurenineL-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin. It has been associated with tics.Kynureninase catabolizes the conversion of kynurenine into anthranilic acid while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid...
in a reaction catalyzed by the enzyme kynurenine—oxoglutarate transaminase.
Mechanism of action
KYNA has been found to act on three receptors:
- As a noncompetitive antagonist at the glycine site of the NMDA receptorNMDA receptorThe NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
. - As an antagonist of the α7 nicotinic acetylcholine receptorAlpha-7 nicotinic receptorThe alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor, consisting entirely of α7 subunits....
. This action has been recently disputed and if true is contrary to another tryptophan metabolite, 5-hydroxyindoleacetic acid5-Hydroxyindoleacetic acid5-Hydroxyindoleacetic acid is the main metabolite of serotonin in the human body. In chemical analysis of urine samples, 5-HIAA is used to determine the body's levels of serotonin.- Clinical significance :...
.
Role in disease
High levels of kynurenic acid have been identified in patients suffering from tick-borne encephalitis, schizophreniaSchizophreniaSchizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
and HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
-related illnesses. In all these situations increased levels were associated with confusion and psychotic symptoms. Kynurenic acid acts in the brainBrainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
as a glycine-site NMDArNMDA receptorThe NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
antagonist, key in glutamatergic neurotransmission system, which is thought to be involved in the pathophysiologyPathophysiologyPathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
and pathogenesisPathogenesisThe pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...
of schizophrenia.
A kynurenic acid hypothesis of schizophrenia has been proposed in 2007, based on its action on midbrain dopamine activity and NMDArs, thus linking dopamine hypothesis of schizophreniaDopamine hypothesis of schizophreniaThe dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model attributing symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have...
with the glutamate hypothesisGlutamate hypothesis of schizophreniaThe glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms linked to glutamatergic signaling. The hypothesis was initially based on a set of clinical, neuropathological, and, later, genetic findings pointing at a hypofunction of glutamatergic signaling via NMDA receptors...
of the disease.
High levels of kynurenic acid have been identified in human urine in certain metabolic disorders, such as marked pyridoxine deficiencyPyridoxine deficiencyPyridoxine deficiency is a paediatric disease due to a lack of pyridoxine . It usually becomes noticeable within the first 12 months of life in infants with a lack of pyridoxine, a coenzyme responsible for numerous essential metabolic reactions in humans...
and deficiency/absence of kynureninaseKynureninaseKynureninase or L-Kynurenine hydrolase is a PLP dependent enzyme that catalyses the cleavage of kynurenine into anthranilic acid . It can also act on 3hKyn and some other -alanines...
.
When researchers decreased the levels of kynurenic acid in the brains of mice, the cognition was shown to improve markedly.
External links
- Link found between TBE and schizophrenia - TheLocal.se, Sweden's news in English, 6 November 2007.
- As a noncompetitive antagonist at the glycine site of the NMDA receptor