Monoamine oxidase A, also known as MAO-A, is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that in
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
s is encoded by the ''MAOA''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
This gene is one of two neighboring gene family members that encode
mitochondria
A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...
l enzymes which
catalyze
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
the
oxidative
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
deamination
Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases.
In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of e ...
of
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...
s, such as
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
,
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
, and
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
. A mutation of this gene results in
Brunner syndrome
Brunner syndrome is a rare genetic disorder associated with a mutation in the MAOA gene. It is characterized by lower than average IQ (typically about 85), problematic impulsive behavior (such as pyromania, hypersexuality and violence), sleep d ...
. This gene has also been associated with a variety of other psychiatric disorders, including
antisocial
Antisocial may refer to:
Sociology, psychiatry and psychology
*Anti-social behaviour
*Antisocial personality disorder
*Psychopathy
*Conduct disorder
Law
*Anti-social Behaviour Act 2003
*Anti-Social Behaviour Order
*Crime and Disorder Act 1998
* ...
behavior.
Alternatively spliced
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be ...
transcript variants encoding multiple isoforms have been observed.
Structures
Gene
Monoamine oxidase
Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first ...
A, also known as MAO-A, is an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that in
human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
s is encoded by the ''MAOA''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
The promoter of ''MAOA'' contains conserved binding sites for
Sp1,
GATA2
GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of bl ...
, and
TBP.
This gene is adjacent to a related gene (''
MAOB
Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the ''MAOB'' gene.
The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. I ...
'') on the opposite strand of the
X chromosome
The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex-d ...
.
In humans, there is a 30-base
repeat sequence repeated several different numbers of times in the
promoter region
In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of i ...
of MAO-A. There are 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence, with the 3R and 4R variants most common in all populations. The 3.5R and 4R variants have been found to be more highly active than 3R or 5R, in a study which did not examine the 2R variant.
Several studies have found differences in the frequency distribution of variants of the ''MAOA'' promoter repeat between ethnic groups: 52-59% of African American men,
48-62% of Chinese men,
62% of Maori men,
57% of Japanese men,
and 33-37% of European men
carried the 3R allele, while 5.5% of Black men, 0.1% of Caucasian men, and 0.00067% of Asian men carried the 2R allele. However, amongst White European men, there was a large range of variability based on ethnicity. Men from Latin Europe had low instances of the gene, but Central and Eastern European men had higher prevalences of the 3R allele, with Czechs, Polish, and Ukrainians having the higher than average prevalence.
The
epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
modification of ''MAOA'' gene expression through methylation likely plays an important role in women.
A study from 2010 found epigenetic methylation of ''MAOA'' in men to be very low and with little variability compared to women, while having higher heritability in men than women.
Protein
The gene encodes a
monomeric
In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization.
Classification
Mo ...
protein which shares a 70%
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
sequence identity, as well as conserved chain folds and
flavin adenine dinucleotide
Flavin may refer to:
Placename
* Flavin, Aveyron, a commune in southern France
Surname
* Adrian Flavin (born 1979), a professional rugby player
* Christopher Flavin, president of the Worldwatch Institute
* Dan Flavin (1933–1996), a minimalis ...
(FAD)-binding site structures, with MAO-B. However, MAO-A has a monopartite cavity of approximately 550
angstrom
The angstromEntry "angstrom" in the Oxford online dictionary. Retrieved on 2019-03-02 from https://en.oxforddictionaries.com/definition/angstrom.Entry "angstrom" in the Merriam-Webster online dictionary. Retrieved on 2019-03-02 from https://www.m ...
s, compared to the 290-angstrom bipartite cavity in MAO-B. Nonetheless, both proteins adopt
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ...
ic forms when membrane-bound. The
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
domain of MAO-A forms helical tails which are responsible for attaching the protein to the
outer mitochondrial membrane
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...
(OMM). MAO-A contains loop structures at the entrance of its
active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...
.
Function
MAO-A is a key regulator for normal brain function. It is a
flavoenzyme
Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin.
Flavoproteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repai ...
which degrades amine
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
s, such as dopamine, norepinephrine, and serotonin, via
oxidative
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
deamination
Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases.
In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of e ...
. It is highly expressed in
neural
In Biology, biology, the nervous system is the Complex system, highly complex part of an animal that coordinates its Behavior, actions and Sense, sensory information by transmitting action potential, signals to and from different parts of its ...
and
cardiac cells and
localizes to the
outer mitochondrial membrane
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...
. Its expression is regulated by the
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s SP1, GATA2, and TBP via the
CAMP
Camp may refer to:
Outdoor accommodation and recreation
* Campsite or campground, a recreational outdoor sleeping and eating site
* a temporary settlement for nomads
* Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...
pathway in response to stress such as
ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
and
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
.
[ One behavioral study suggested a link between the 2R allele and a higher likelihood of violent behavior in adolescents and young adults while another showed no link at all with either antisocial behavior or antisocial alcoholism.]
Clinical significance
Cancer
MAO-A produces an amine oxidase, which is a class of enzyme known to affect carcinogenesis. Clorgyline
Clorgiline (INN), or clorgyline ( BAN), is a monoamine oxidase inhibitor (MAOI) structurally related to pargyline which is described as an antidepressant. Specifically, it is an irreversible and selective inhibitor of monoamine oxidase A (MAO ...
, an MAO-A enzyme inhibitor, prevents apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
in melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
cells, in vitro. Cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stool ...
suppresses MAO-A expression, and those patients with higher MAO-A expression had less adjacent organ invasion and better prognosis and survival.
Cardiovascular disease
MAOA activity is linked to apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
and cardiac damage during cardiac injury following ischemic- reperfusion.[
]
Behavioral and neurological disorders
There is some association between low activity forms of the ''MAOA'' gene and autism
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental condition (or conditions) characterized by difficulti ...
. Mutations in the MAOA gene results in monoamine oxidase deficiency, or Brunner syndrome
Brunner syndrome is a rare genetic disorder associated with a mutation in the MAOA gene. It is characterized by lower than average IQ (typically about 85), problematic impulsive behavior (such as pyromania, hypersexuality and violence), sleep d ...
. Other disorders associated with MAO-A include Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
, aggression
Aggression is overt or covert, often harmful, social interaction with the intention of inflicting damage or other harm upon another individual; although it can be channeled into creative and practical outlets for some. It may occur either reacti ...
, panic disorder
Panic disorder is a mental disorder, mental and Abnormal behavior, behavioral disease#Disorder, disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear th ...
, 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 ...
, major depressive disorder
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 ...
, and attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
. Effects of parenting on self-regulation in adolescents appear to be moderated by 'plasticity alleles', of which the 2R and 3R alleles of MAOA are two, with "the more plasticity alleles males (but not females) carried, the more and less self-regulation they manifested under, respectively, supportive and unsupportive parenting conditions."
Depression
MAO-A levels in the brain as measured using positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...
are elevated by an average of 34% in patients with major depressive disorder
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 ...
. Genetic association studies examining the relationship between high-activity ''MAOA'' variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females, depressed suicide in males, major depression and sleep disturbance in males and major depressive disorder in both males and females.
Other studies failed to find a significant relationship between high-activity variants of the ''MAOA'' gene and major depressive disorder. In patients with major depressive disorder, those with MAOA G/T polymorphisms (rs6323) coding for the highest-activity form of the enzyme have a significantly lower magnitude of placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
response than those with other genotypes.
Antisocial behavior
In humans, an association between the 2R allele of the VNTR
A variable number tandem repeat (or VNTR) is a location in a genome where a short nucleotide sequence is organized as a tandem repeat. These can be found on many chromosomes, and often show variations in length (number of repeats) among individ ...
region of the gene and an increase in the likelihood of committing serious crime or violence has been found. The VNTR 2R allele of MAOA has been found to be a risk factor for violent delinquency, when present in association with stresses, i.e. family issues, low popularity or failing school.
A connection between the ''MAO-A'' gene 3R version and several types of anti-social behaviour
Antisocial behavior is a behavior that is defined as the violation of the rights of others by committing crime, such as stealing and physical attack in addition to other behaviors such as lying and manipulation. It is considered to be disrupti ...
has been found: Maltreated children with genes causing high levels of MAO-A were less likely to develop antisocial behavior.[
*] Low MAO-A activity alleles which are overwhelmingly the 3R allele in combination with abuse experienced during childhood resulted in an increased risk of aggressive behaviour as an adult, and men with the low activity MAOA allele were more genetically vulnerable even to punitive discipline as a predictor of antisocial behaviour. High testosterone, maternal tobacco smoking during pregnancy, poor material living standards, dropping out of school, and low IQ predicted violent behavior are associated with men with the low-activity alleles. According to a large meta-analysis in 2014, the 3R allele had a small, nonsignificant effect on aggression and antisocial behavior, in the absence of other interaction factors. Owing to methodological concerns, the authors do not view this as evidence in favor of an effect.
The ''MAO-A'' gene was the first candidate gene for antisocial behavior and was identified during a "molecular genetic analysis of a large, multigenerational, and notoriously violent, Dutch kindred". A study of Finnish prisoners revealed that a MAOA-L (low-activity) genotype, which contributes to low dopamine turnover rate, was associated with extremely violent behavior. For the purpose of the study, "extremely violent behavior" was defined as at least ten committed homicides, attempted homicides or batteries.
However, a large genome-wide association study has failed to find any large or statistically significant effects of the MAOA gene on aggression. A separate GWAS on antisocial personality disorder likewise did not report a significant effect of MAOA. Another study, while finding effects from a candidate gene search, failed to find any evidence in a large GWAS. A separate analysis of human and rat genome wide association studies, Mandelian randomization studies, and causal pathway analyses likewise failed to reveal robust evidence of MAOA in aggression. This lack of replication is predicted from the known issues of candidate gene research, which can produce many substantial false positives.
Aggression and the "Warrior gene"
Low-activity variants of the VNTR promoter region of the ''MAO-A'' gene have been referred to as the ''warrior gene''. While almost all humans have a functional MAO-A gene, MAO-A deficiency has been seen in at least 5 families with Brunner syndrome
Brunner syndrome is a rare genetic disorder associated with a mutation in the MAOA gene. It is characterized by lower than average IQ (typically about 85), problematic impulsive behavior (such as pyromania, hypersexuality and violence), sleep d ...
.
Given that MAO-A degrades amine neurotransmitters, gene variants could affect a person's personality or behaviour. When faced with social exclusion or ostracism, individuals with the low activity ''MAO-A'' variants showed higher levels of aggression than individuals with the high activity ''MAO-A'' gene. Low activity MAO-A could significantly predict aggressive behaviour in a high provocation situation, but was less associated with aggression in a low provocation situation. Individuals with the low activity variant of the ''MAO-A'' gene were just as likely as participants with the high activity variant to retaliate (by administering hot sauce to an opponent) when the loss was small. However, they were more likely (75% as opposed to 62%, out of a sample size of 70) to retaliate and with greater force when the loss was large.
The effects of MAOA genes on aggression have also been criticized for being heavily overstated. Indeed, the MAOA gene, even in conjunction with childhood adversity, is known to have a very small effect. The vast majority of people with the associated alleles have not committed any violent acts.
Legal implications
In a 2009 criminal trial in the United States, an argument based on a combination of "warrior gene" and history of child abuse
Child abuse (also called child endangerment or child maltreatment) is physical, sexual, and/or psychological maltreatment or neglect of a child or children, especially by a parent or a caregiver. Child abuse may include any act or failure to a ...
was successfully used to avoid a conviction of first-degree murder
Murder is the unlawful killing of another human without justification or valid excuse, especially the unlawful killing of another human with malice aforethought. ("The killing of another person without justification or excuse, especially the c ...
and the death penalty; however, the convicted murderer was sentenced to 32 years in prison.
Epigenetics
Studies have linked methylation of the ''MAOA'' gene with nicotine and alcohol dependence in women. A second ''MAOA'' VNTR promoter, P2, influences epigenetic methylation and interacts with having experienced child abuse to influence antisocial personality disorder symptoms, only in women.
Animal studies
A dysfunctional ''MAOA'' gene has been correlated with increased aggression levels in mice, and has been correlated with heightened levels of aggression in humans. In mice, a dysfunctional ''MAOA'' gene is created through insertional mutagenesis (called 'Tg8'). Tg8 is a transgenic mouse strain that lacks functional MAO-A enzymatic activity. Mice that lacked a functional ''MAOA'' gene exhibited increased aggression towards intruder mice.
Some types of aggression exhibited by these mice were territorial aggression, predatory aggression, and isolation-induced aggression. The MAO-A deficient mice that exhibited increased isolation-induced aggression reveals that an MAO-A deficiency may also contribute to a disruption in social interactions. There is research in both humans and mice to support that a nonsense point mutation in the eighth exon of the ''MAOA'' gene is responsible for impulsive aggressiveness due to a complete MAO-A deficiency.
Interactions
Transcription factors
A number of transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s bind to the promoter region of MAO-A and upregulate
In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pro ...
its expression. These include:Sp1 transcription factor
Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.
Function
The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promote ...
, GATA2
GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of bl ...
, TBP.[
]
Inducers
Synthetic compounds that up-regulate the expression of MAO-A include Valproic acid
Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...
(Depakote)
Inhibitors
Substances that inhibit the enzymatic activity of MAO-A include:
*Synthetic compounds
** Befloxatone
Befloxatone (MD-370,503) is a reversible inhibitor of monoamine oxidase A.
References
Reversible inhibitors of MAO-A
Monoamine oxidase inhibitors
Trifluoromethyl compounds
Secondary alcohols
3-(4-methoxyphenyl)-2-oxazolidinones
{ ...
(MD370503)
** Brofaromine (Consonar)
** Cimoxatone
Cimoxatone (MD 780515) is a reversible inhibitor of MAO-A (RIMA). It has a significant food interaction–related adverse effect in combination with tyramine
Tyramine ( ) (also spelled tyramin), also known under several other names, is a na ...
** Clorgyline
Clorgiline (INN), or clorgyline ( BAN), is a monoamine oxidase inhibitor (MAOI) structurally related to pargyline which is described as an antidepressant. Specifically, it is an irreversible and selective inhibitor of monoamine oxidase A (MAO ...
(irreversible)
** Methylene Blue
Methylthioninium chloride, commonly called methylene blue, is a salt used as a dye and as a medication. Methylene blue is a thiazine dye. As a medication, it is mainly used to treat methemoglobinemia by converting the ferric iron in hemoglobin ...
** Minaprine
Minaprine ( INN, USAN, BAN) (brand names Brantur, Cantor) is a monoamine oxidase inhibitor antidepressant drug that was used in France for the treatment of depression until it was withdrawn from the market in 1996 because it caused convulsion ...
(Cantor)
** Moclobemide
Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in t ...
(Aurorix, Manerix)
** Phenelzine
Phenelzine, sold under the brand name Nardil, among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is primarily used as an antidepressant and anxiolytic. Along with tranylcypromine and ...
(Nardil)
** Pirlindole
Pirlindole (Lifril, Pyrazidol) is mainly a reversible inhibitor of monoamine oxidase A (RIMA) and secondly a SNRI which was developed and is used in Russia as an antidepressant. It is structurally and pharmacologically related to metralindole. ...
(Pirazidol)
** Toloxatone
Toloxatone (Humoryl) is an antidepressant launched in 1984 in France by Sanofi Aventis for the treatment of depression. It was discontinued in 2002. It acts as a selective reversible inhibitor of MAO-A
Monoamine oxidase inhibitors (MAOIs) ...
(Humoryl)
** Tyrima
CX157 (proposed trade name TriRima, formerly Tyrima) is a binding selectivity, selective and reversible inhibitor of monoamine oxidase A, reversible inhibitor of MAO-A (RIMA). As of 2007 it was in phases of clinical research, phase II clinical tr ...
(CX 157)
** Tranylcypromine
Tranylcypromine, sold under the brand name Parnate among others,Drugs.co Page accessed April 17, 2016 is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme mono ...
(nonselective and irreversible)
*Natural products
** Incarviatone A
*Herbal sources
** Garlic
Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
(Garlic
Garlic (''Allium sativum'') is a species of bulbous flowering plant in the genus ''Allium''. Its close relatives include the onion, shallot, leek, chive, Allium fistulosum, Welsh onion and Allium chinense, Chinese onion. It is native to South A ...
)
** β-Carboline alkaloids (Syrian Rue
''Peganum harmala'', commonly called wild rue, Syrian rue, African rue, esfand or espand,Mahmoud OmidsalaEsfand: a common weed found in Persia, Central Asia, and the adjacent areasEncyclopedia Iranica Vol. VIII, Fasc. 6, pp. 583–584. Originall ...
, Passion Flower
''Passiflora'', known also as the passion flowers or passion vines, is a genus of about 550 species of flowering plants, the type genus of the family Passifloraceae.
They are mostly tendril-bearing vines, with some being shrubs or trees. The ...
, Tobacco smoke
Tobacco smoke is a sooty aerosol produced by the incomplete combustion of tobacco during the tobacco smoking, smoking of cigarettes and other tobacco products. Temperatures in burning cigarettes range from about 400 °C between puffs to abo ...
, Ayahuasca
AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' (Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' descen ...
)
*** Harmine
Harmine is a beta-carboline and a harmala alkaloid. It occurs in a number of different plants, most notably the Syrian rue and ''Banisteriopsis caapi''. Harmine reversibly inhibits monoamine oxidase A (MAO-A), an enzyme which breaks down monoamin ...
*** Harmaline
Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the partly hydrogenated form of harmine.
Occurrence in nature
Various plants contain harmaline including ''Peganum harmala'' (Syrian rue) ...
** Isoquinoline alkaloids
Isoquinoline alkaloids are natural products of the group of alkaloids, which are chemically derived from isoquinoline. They form the largest group among the alkaloids.
Isoquinoline alkaloids can be further classified based on their different chem ...
** Piperine
Piperine, along with its isomer chavicine, is the alkaloid responsible for the pungency of black pepper and long pepper. It has been used in some forms of traditional medicine.
Preparation
Due to its poor solubility in water, piperine is typica ...
(Black pepper
Black pepper (''Piper nigrum'') is a flowering vine in the family Piperaceae, cultivated for its fruit, known as a peppercorn, which is usually dried and used as a spice and seasoning. The fruit is a drupe (stonefruit) which is about in diame ...
)
** Rosiridin
Rosiridin is a chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule cons ...
(''in vitro'')
See also
* Monoamine oxidase B
Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the ''MAOB'' gene.
The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. ...
* Monoamine oxidase inhibitor
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espe ...
- a class of antidepressant drugs that block or inactivate one or both MAO isoforms
References
Further reading
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External links
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{{DEFAULTSORT:Monoamine Oxidase A
Aggression
EC 1.4.3
Human proteins
de:Warrior Gene