Monoaminooxidases (MAO) are enzymes responsible for the breakdown of monoamines in the body. Many monoamines are neurotransmitters and are involved in the transmission of stimuli within the nervous system. A lack of activity of monoamine oxidases can lead to aggressive behavior.
What is a monoamine oxidase?
Monoaminooxidases represent enzymes that specialize in the breakdown of monoamines in the body. In this process, monoamines are converted into the corresponding aldehydes, ammonia, and hydrogen peroxide with the help of water and oxygen. Many monoamines function as neurotransmitters and are responsible for the transmission of stimuli within the nervous system. Thus, when the concentration of these substances in the organism increases, the result is increased irritability. Monoaminooxidases ensure that monoamines do not accumulate in the body. Monoaminooxidase is located in the outer mitochondrial membrane of every eukaryotic cell. If for some reason there is a deficiency of neurotransmitters of the monoamine group, depression may result. In these cases, the use of MAO inhibitors then helps, as they prevent the degradation of the remaining monoamines by monoaminooxidase. The monoaminooxidases occur in two groups. In the human organism and in mammals, both monoaminooxidase-A and monoaminooxidase-B are active. Monoaminooxidase-A, however, is already present in fungi, while monoaminooxidase-B acts only in mammalian cells. Both enzymes partially degrade different monoamines. Monoaminooxidase-A, for example, is responsible for the degradation of serotonin, melatonin, adrenaline or noradrenaline. Monoaminooxidase-B catalyzes the degradation of benzylamine and phenethylamine. The monoamines dopamine, tryptamine, or tyramine can be degraded equally by both monoaminooxidases.
Function, action, and tasks
Monoaminooxidases thus possess the important task of degrading and thus inactivating all monoamines occurring in metabolism. The neurotransmitters among them have a major impact on bodily processes. Other monoamines are simply intermediates in the breakdown of certain amino acids, which are then further broken down by MAO. As mentioned above, monoamines are converted into the homologous aldehydes, ammonia and hydrogen peroxide with the participation of water and oxygen. The corresponding aldehydes undergo further reduction to alcohols, which in turn are oxidized to the biologically inactive acid. The end products of monoamine degradation are excreted in the urine. In addition to monoamines formed in the body, monoamines supplied by food, such as tyramine from cheese, are also degraded by monoaminooxidase. The biological significance of MAO is that it prevents toxic monoamines from being stored in the body. The accumulation of neurotransmitters in the nervous system significantly increases the irritability of the organism. This causes aggressive and impulsive behavior. Other monoamines occur as intermediate products of metabolism and act as poisons when accumulated in the organism. Therefore, the breakdown of monoamines by MAO can also be considered as detoxification of the body.
Formation, occurrence, properties, and optimal values
Both monoamine oxidases are encoded by genes located on the short arm of the X chromosome. Monoaminooxidase-A exerts its functions outside the brain in the sympathetic and enteric nervous systems. By breaking down monoamines in these areas, it regulates digestive activity, blood pressure, cardiac activity, all other organ activities and metabolism. The higher the concentration of neurotransmitters there, the more irritable a person is. Monoaminooxidase-B acts in the central nervous system and is responsible for the breakdown of beta-phenylethylamine (PEA) and benzylamine. In addition, like monoaminooxidase-A, it is also involved in the breakdown of dopamine.
Diseases and disorders
Several studies have found that a deficiency of monoaminooxidase-A leads to antisocial and aggressive behavior. This can be explained by the fact that the accumulation of neurotransmitters in the nervous system leads to increased irritability because the transmission of stimuli in the nervous system is enhanced. The willingness to take risks also increases. Relatedly, there was also a negative correlation between monoamine oxidase A deficiency and debt. The complete failure of monoaminooxidase-A leads to the so-called Brunner syndrome.Brunner’s syndrome is genetic and is characterized by extreme impulsive aggressiveness to the point of violence and mild intellectual deficit. The symptoms appear already in childhood. The disease is inherited in an x-chromosonal recessive manner. Mainly males are affected because they have only one X chromosome. When a defective gene occurs, there is no compensating normal gene. A tendency to physically risky activities, disinhibition in the form of promiscuity, drinking or party addiction, as well as a tendency to restlessness in an environment poor in variety were also observed in the case of a deficiency in monoaminooxidase-B. At the same time, the tendency to aggressiveness and violence was also increased. However, the full activity of monoaminooxidases is not always desired. A deficiency of neurotransmitters such as serotonin or dopamine leads to depression. In these cases, monoaminooxidase or MAO inhibitors help to restore the concentration of these neurotransmitters to normal. MAO inhibitors suppress the function of monoaminooxidases. The breakdown of monoamines can no longer take place, so they accumulate again. Since Parkinson’s disease is also caused by a lack of dopamine, it too can be treated with monoaminooxidase inhibitors. Selective monoaminooxidase B inhibitors such as selegelin or rasagiline are used. Non-selective Mao inhibitors for monoaminooxidase-A and monoaminooxidase-B can be used to treat depression and anxiety disorders. Furthermore, there are selective monoaminooxidase-A inhibitors for the treatment of depression. In addition, reversible and irreversible MAO inhibitors are used. The irreversible monoamine oxidase inhibitors bind so tightly to monoamine oxidase that it cannot be released after treatment, but must be regenerated over an extended period of time.
