-Kynurenine is a metabolite of the amino acid -

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

used in the production of

niacin Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...

. Kynurenine is synthesized by the enzyme tryptophan dioxygenase, which is made primarily but not exclusively in the liver, and

indoleamine 2,3-dioxygenase Indoleamine-pyrrole 2,3-dioxygenase (IDO or INDO ) is a heme-containing enzyme physiologically expressed in a number of tissues and cells, such as the small intestine, lungs, female genital tract or placenta. In humans is encoded by the ''IDO1' ...

, which is made in many tissues in response to immune activation. Kynurenine and its further breakdown products carry out diverse biological functions, including dilating blood vessels during inflammation and regulating the immune response. Some cancers increase kynurenine production, which increases tumor growth. Evidence suggests that increased kynurenine production may precipitate depressive symptoms associated with interferon treatment for hepatitis C. Cognitive deficits in

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

are associated with imbalances in the enzymes that break down kynurenine. Blood levels of kynurenine are reduced in people with

bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...

. Kynurenine production is increased in Alzheimer's disease and cardiovascular disease where its metabolites are associated with cognitive deficits and depressive symptoms. Kynurenine is also associated with

tic A tic is a sudden, repetitive, nonrhythmic motor movement or vocalization involving discrete muscle groups.American Psychiatric Association (2000)DSM-IV-TR: Tourette's Disorder.''Diagnostic and Statistical Manual of Mental Disorders'', 4th ed., ...

Kynureninase Kynureninase or L-Kynurenine hydrolase (KYNU) () is a PLP dependent enzyme that catalyses the cleavage of kynurenine (Kyn) into anthranilic acid (Ant). It can also act on 3-hydroxykynurenine (to produce 3-hydroxyanthranilate) and some other (3 ...

catabolizes the conversion of kynurenine into

anthranilic acid Anthranilic acid is an aromatic acid with the formula C6H4(NH2)(CO2H) and has a sweetish taste. The molecule consists of a benzene ring, ''ortho''-substituted with a carboxylic acid and an amine. As a result of containing both acidic and basic ...

while kynurenine-oxoglutarate transaminase catabolizes its conversion into

kynurenic acid Kynurenic acid (KYNA or KYN) is a product of the normal metabolism of amino acid -tryptophan. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an ...

. Kynurenine 3-hydroxylase converts kynurenine to 3-hydroxykynurenine. Kynurenine has also been identified as one of two compounds that makes up the pigment that gives the

goldenrod crab spider ''Misumena vatia'' is a species of crab spider with a holarctic distribution. In North America, it is called the goldenrod crab spider or flower (crab) spider,Acorn, John and Sheldon, Ian. (2003). ''Bugs of Ontario'' Edmonton: Lone Pine Publish ...

its yellow color. 280px, left, The Kynurenine_pathway,_which_connects_quinolinic_acid_to_tryptophan._The_pathway_is_named_for_the_first_intermediate,_kynurenine,_which_is_a_precursor_to_kynurenic_acid_ Kynurenic_acid_(KYNA_or_KYN)_is_a_product_of_the_normal_metabolism_of_amino_acid_-tryptophan._It_has_been_shown_that_kynurenic_acid_possesses_neuroactive_activity._It_acts_as_an__antiexcitotoxic_and_anticonvulsant,_most_likely_through_acting_as_an_...

Kynurenine pathway dysfunction

quinolinic acid Quinolinic acid (abbreviated QUIN or QA), also known as pyridine-2,3-dicarboxylic acid, is a dicarboxylic acid with a pyridine backbone. It is a colorless solid. It is the biosynthetic precursor to niacin. Quinolinic acid is a downstream produc ...

HIV dementia HIV-associated neurocognitive disorders (HAND) are neurological disorders associated with HIV infection and AIDS. It is a syndrome of progressive deterioration of memory, cognition, behavior, and motor function in HIV-infected individuals during ...

Tourette syndrome Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...

Tic disorders Tic disorders are defined in the ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM) based on type (motor or phonic) and duration of tics (sudden, rapid, nonrhythmic movements). Tic disorders are defined similarly by the World Health ...

Psychiatric disorders A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...

major depression Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...

anxiety disorders Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...

) * Multiple sclerosis *

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...

Encephalopathies Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...

Lipid metabolism Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In anim ...

* Liver fat metabolism * Systemic lupus erythematosus * Glutaric aciduria * Vitamin B₆ deficiency * Eosinophilia-myalgia syndrome * Myalgic encephalomyelitis / chronic fatigue syndrome Downregulation of kynurenine-3-monooxygenase (KMO) can be caused by genetic polymorphisms, cytokines, or both. KMO deficiency leads to an accumulation of kynurenine and to a shift within the tryptophan

metabolic pathway In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical reac ...

towards kynurenine acid and

. Kynurenine-3-monooxygenase deficiency is associated with disorders of the brain (e.g. major depressive disorder, bipolar disorder, schizophrenia, tic disorders) and of the liver.

References

{{Ionotropic glutamate receptor modulators Amino acids Human metabolites NMDA receptor antagonists

Kynurenine pathway dysfunction

See also

References