-Kynurenine is a
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
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
Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten the ...
treatment for
hepatitis C
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...
. 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 withdra ...
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., ...
s.
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 f ...
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
In enzymology, a kynurenine 3-monooxygenase () is an enzyme that catalyzes the chemical reaction
: -kynurenine + NADPH + H+ + O2 3-hydroxy--kynurenine + NADP+ + H2O
Kynurenine 3-monooxygenase is the expression product of the KMO (gene). Th ...
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_...
_and_3-Hydroxykynurenine.html" ;"title="quinolinic_acid.html" ;"title="Kynurenine pathway, which connects quinolinic acid">Kynurenine pathway, which connects quinolinic acid to tryptophan. The pathway is named for the first intermediate, kynurenine, which is a precursor to
and 3-Hydroxykynurenine">3-hydroxykynurenine.
Dysfunctional states of distinct steps of the kynurenine pathway (such as kynurenine,
, 3-hydroxykynurenine) have been described for a number of disorders, including:
*
, or both.
KMO deficiency leads to an accumulation of kynurenine and to a shift within the tryptophan
.
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.
