Monoamine oxidases (singular abbreviation
MAO) are
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
s that
catalyzeCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was discovered by Mary Hare in the
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, and received the name of tyramine oxidase. They belong to
protein familyA protein family is a group of evolutionarily related proteins, and is often nearly synonymous with gene family. The term protein family should not be confused with family as it is used in taxonomy....
of flavin-containing amine oxidoreductases.
In humans there are two types of MAO:
MAO-AMonoamine oxidase A, also known as MAOA, is an enzyme which in humans is encoded by the MAOA gene. Monoamine oxidase A is an isozyme of monoamine oxidase. It preferentially deaminates norepinephrine , epinephrine , serotonin, and dopamine...
and MAO-B.
- Both are found in neuron
A neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
s and astroglia.
- Outside the central nervous system
The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
:
- MAO-A is also found in the liver
The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, gastrointestinal tractThe human gastrointestinal tract , digestive tract, guts or gut is the system of organs within humans that takes in food, digests it to extract energy and nutrients, and expels the remaining matter...
, and placentaThe placenta is an organ unique to mammals that connects the developing fetus to the uterine wall. The placenta supplies the fetus with oxygen and food, and allows fetal waste to be disposed of via the maternal kidneys...
.
- MAO-B is mostly found in blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells — such as nutrients and oxygen — and transports waste products away from those same cells....
plateletPlatelets, or thrombocytes , are small, irregularly-shaped anuclear cells , 2-3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is between 8 and 12 days...
s.
Monoamine oxidases catalyze the
oxidative deaminationOxidative deamination is a form of deamination that generates oxoacids in the liver.The presence of nitrous acid can cause transition mutations, by converting cytosine to uracil.-In Urea cycle:...
of monoamines.
Monoamine oxidases (singular abbreviation
MAO) are
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
s that
catalyzeCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was discovered by Mary Hare in the
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, and received the name of tyramine oxidase. They belong to
protein familyA protein family is a group of evolutionarily related proteins, and is often nearly synonymous with gene family. The term protein family should not be confused with family as it is used in taxonomy....
of flavin-containing amine oxidoreductases.
Locations of MAO-A and MAO-B
In humans there are two types of MAO:
MAO-AMonoamine oxidase A, also known as MAOA, is an enzyme which in humans is encoded by the MAOA gene. Monoamine oxidase A is an isozyme of monoamine oxidase. It preferentially deaminates norepinephrine , epinephrine , serotonin, and dopamine...
and MAO-B.
- Both are found in neuron
A neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
s and astroglia.
- Outside the central nervous system
The central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
:
- MAO-A is also found in the liver
The liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, gastrointestinal tractThe human gastrointestinal tract , digestive tract, guts or gut is the system of organs within humans that takes in food, digests it to extract energy and nutrients, and expels the remaining matter...
, and placentaThe placenta is an organ unique to mammals that connects the developing fetus to the uterine wall. The placenta supplies the fetus with oxygen and food, and allows fetal waste to be disposed of via the maternal kidneys...
.
- MAO-B is mostly found in blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells — such as nutrients and oxygen — and transports waste products away from those same cells....
plateletPlatelets, or thrombocytes , are small, irregularly-shaped anuclear cells , 2-3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is between 8 and 12 days...
s.
Function
Monoamine oxidases catalyze the
oxidative deaminationOxidative deamination is a form of deamination that generates oxoacids in the liver.The presence of nitrous acid can cause transition mutations, by converting cytosine to uracil.-In Urea cycle:...
of monoamines.
OxygenOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
is used to remove an
amineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
group from a molecule, resulting in the corresponding
aldehydeAn aldehyde is an organic compound containing a terminal carbonyl group. This functional group, which consists of a carbon atom bonded to a hydrogen atom and double-bonded to an oxygen atom , is called the aldehyde group...
and
ammoniaAmmonia is a compound of nitrogen and hydrogen with the formula NH
3. It is normally encountered as a gas with a characteristic pungent odor. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to foodstuffs and fertilizers...
. The general form of the catalyzed reaction (with R denoting an arbitrary group) is:
Monoamine
oxidaseAn oxidase is any enzyme that catalyzes an oxidation/reduction reaction involving molecular oxygen as the electron acceptor. In these reactions, oxygen is reduced to water or hydrogen peroxide ....
s contain the covalently-bound
cofactorA cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes and cofactors can be considered "helper molecules/ions" that assist in biochemical transformations...
FADIn biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states and its biochemical role usually involves changing between these two states...
and are, thus, classified as
flavoproteinFlavoproteins are proteins that contain a nucleic acid derivative of riboflavin: the flavin adenine dinucleotide or flavin mononucleotide ....
s.
Subtype Specificities
MAO-A is particularly important in the
catabolismCatabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides and amino...
of monoamines ingested in food. Both MAOs are also vital to the inactivation of monoaminergic
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
s, for which they display different specificities.
- Serotonin
Serotonin is a monoamine neurotransmitter. It is found extensively in the gastrointestinal tract of animals, and about 80 to 90 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements...
, norepinephrineNoradrenaline or norepinephrine is a catecholamine with dual roles as a hormone and a neurotransmitter....
(noradrenaline), and epinephrineEpinephrine is a hormone and neurotransmitter that participates in the "fight or flight" response of the sympathetic nervous system...
(adrenaline) are mainly broken down by MAO-A.
- Phenethylamine
Phenethylamine is a natural monoamine alkaloid, trace amine, and psychoactive drug with stimulant effects. In the mammalian central nervous system, phenethylamine is believed to function as a neuromodulator or neurotransmitter. It is biosynthesized from the amino acid phenylalanine by enzymatic...
is mainly broken down by MAO-B.
- Both forms break down dopamine
Dopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors — D
1, D
2, D
3, D
4, and...
equally.
Specific reactions catalyzed by MAO include:
- epinephrine
Epinephrine is a hormone and neurotransmitter that participates in the "fight or flight" response of the sympathetic nervous system...
or norepinephrineNoradrenaline or norepinephrine is a catecholamine with dual roles as a hormone and a neurotransmitter....
to 3,4-Dihydroxymandelic acid3,4-Dihydroxymandelic acid is a metabolite of norepinephrine.-References:...
- metanephrine
Metanephrine is a metabolite of epinephrine created by action of catechol-O-methyl transferase on epinephrine. A March 20, 2002 article in the Journal of the American Medical Association indicated that the measurement of plasma free metanephrines is the best tool in the diagnosis of...
or normetanephrineNormetanephrine is a metabolite of norepinephrine created by action of catechol-O-methyl transferase on norepinephrine. It is excreted in the urine and found in certain tissues. It is a marker for catecholamine-secreting tumors such as pheochromocytoma....
to vanillylmandelic acid (VMA)
- dopamine
Dopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors — D
1, D
2, D
3, D
4, and...
to dihydroxyphenylacetic acid
- 3-Methoxytyramine
3-Methoxytyramine is a metabolite of the neurotransmitter dopamine formed by the introduction of a methyl group to dopamine by the enzyme catechol-O-methyl transferase...
to homovanillic acidHomovanillic acid is a major catecholamine metabolite...
Disorders resulting from MAO dysfunction
Because of the vital role that MAOs play in the inactivation of neurotransmitters, MAO dysfunction (too much or too little MAO activity) is thought to be responsible for a number of neurological disorders. For example, unusually high or low levels of MAOs in the body have been associated with
depressionMajor depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities...
,
schizophreniaSchizophrenia , from the Greek roots skhizein and phrēn, phren- is a psychiatric diagnosis that describes a mental disorder characterized by abnormalities in the perception or expression of reality...
,
substance abuseAlthough the term substance can refer to any physical matter, substance abuse has come to refer to the overindulgence in and dependence of a drug or other chemical leading to effects that are detrimental to the individual's physical and mental health, or the welfare of others.]The disorder is...
, attention deficit disorder, migraines, and irregular sexual maturation.
Monoamine oxidase inhibitorMonoamine oxidase inhibitors are a class of powerful antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression, and have also shown efficacy in smoking cessation....
s are one of the major classes of drug prescribed for the treatment of depression, although they are last-line treatment due to risk of the drug's interaction with diet or other drugs. Excessive levels of
catecholamineCatecholamines are sympathomimetic "fight-or-flight" hormones that are released by the adrenal glands in response to stress. They are part of the sympathetic nervous system....
s (
epinephrineEpinephrine is a hormone and neurotransmitter that participates in the "fight or flight" response of the sympathetic nervous system...
,
norepinephrineNoradrenaline or norepinephrine is a catecholamine with dual roles as a hormone and a neurotransmitter....
, and
dopamineDopamine is a neurotransmitter occurring in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this phenethylamine functions as a neurotransmitter, activating the five types of dopamine receptors — D
1, D
2, D
3, D
4, and...
) may lead to a hypertensive crisis, and excessive levels of
serotoninSerotonin is a monoamine neurotransmitter. It is found extensively in the gastrointestinal tract of animals, and about 80 to 90 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements...
may lead to
serotonin syndromeSerotonin syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs...
.
PETPositron emission tomography is a nuclear medicine imaging technique which produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
research has shown that MAO is also heavily depleted by use of
tobaccoTobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as an organic pesticide, and in the form of nicotine tartrate it is used in some medicines. In consumption it most commonly appears in the forms of smoking, chewing, snuffing, or...
cigarettes.
Genetics
The
geneA gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cells and pass genetic traits to offspring...
s encoding MAO-A and MAO-B are located side-by-side on the short arm of the
X chromosomeThe X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals . It is a part of the XY sex-determination system and X0 sex-determination system...
, and have about 70% sequence similarity. Rare mutations in the gene are associated with
Brunner syndromeBrunner syndrome is a rare genetic disorder with a mutation in the MAOA gene. It is characterised by mild mental retardation and problematic impulsive behavior...
.
A study reported in
ScienceScience is the academic journal of the American Association for the Advancement of Science and is considered one of the world's most prestigious scientific journals. The peer-reviewed journal, first published in 1880 is circulated weekly and has a print subscriber base of around 130,000...
in August 2002 based on the Dunedin cohort concluded that maltreated children with a low-activity polymorphism in the
promoterIn genetics, a promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are typically located near the genes they regulate, on the same strand and upstream .-Overview:...
region of the MAO-A gene were more likely to develop
antisocial conduct disordersConduct disorder is a psychiatric category marked by a pattern of repetitive behavior wherein the rights of others or social norms are violated....
than maltreated children with the high-activity variant. Out of the 442 total males in the study (maltreated or not), 37% had the low activity variant. Of the 13 maltreated males with low MAO-A activity, 11 had been assessed as exhibiting adolescent conduct disorder and 4 were convicted for violent offenses. The suggested mechanism for this effect is the decreased ability of those with low MAO-A activity to quickly degrade norepinephrine, the synaptic neurotransmitter involved in
sympatheticThe Sympathetic Nervous System is a branch of the autonomic nervous system along with the enteric nervous system and parasympathetic nervous system. It is always active at a basal level and becomes more active during times of stress...
arousal and rage. This is alleged to provide direct support for the idea that genetic susceptibility to disease is not determined at birth, but varies with exposure to environmental influences. Note however that most of those with conduct disorder or convictions did not have low activity of MAO-A; maltreatment was found to caused stronger predisposition for antisocial behavior than differences in MAO-A activity.
Research also uncovered a possible link between predisposition to
novelty seekingNeophilia is defined as a love of novelty and new things. A neophiliac or neophile is an individual who is unusually accepting of new things and excited by novelty. The Neophiliacs: Revolution in English Life in the Fifties and Sixties was a 1970 book by Christopher Booker.The word has particular...
and a
genotypeThe genotype is the genetic constitution of a cell, an organism, or an individual usually with reference to a specific character under consideration...
of the MAO-A gene.
In 2006, a New Zealand researcher, Dr Rod Lea said that a particular variant (or
genotypeThe genotype is the genetic constitution of a cell, an organism, or an individual usually with reference to a specific character under consideration...
) was over-represented in
MāoriThe Māori are the indigenous Polynesian people of New Zealand . The group probably arrived in southwestern Polynesia in several waves at some time before 1300...
, a Warrior gene. This supported earlier studies finding different proportions of variants in different ethnic groups. This is the case for many genetic variants, with 33% White/Non-Hispanic, 61% Asian/Pacific Islanders having the low-activity MAO-A
promoterIn genetics, a promoter is a region of DNA that facilitates the transcription of a particular gene. Promoters are typically located near the genes they regulate, on the same strand and upstream .-Overview:...
variant.
See also
- Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of powerful antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression, and have also shown efficacy in smoking cessation....
- Genetics and violence
- Neophilia
Neophilia is defined as a love of novelty and new things. A neophiliac or neophile is an individual who is unusually accepting of new things and excited by novelty. The Neophiliacs: Revolution in English Life in the Fifties and Sixties was a 1970 book by Christopher Booker.The word has particular...
- Warrior gene
- Brunner syndrome
Brunner syndrome is a rare genetic disorder with a mutation in the MAOA gene. It is characterised by mild mental retardation and problematic impulsive behavior...
External links