Monoamine oxidase serotonin oxidation

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

Fuller, R.W. Serotonin oxidation by rat brain monoamine oxidase Inhibition by 4-chloroamphetamine. Life Sci 5 2247-2252, 1966. 

Against this backdrop, researchers reported evidence that iproniazid, the antitubercular drug that was to become the first antidepressant, might increase norepinephrine and serotonin levels in the brain. How did it have this effect Recall that some of the neurotransmitter molecules released by a neuron are destroyed by enzymes in the synaptic cleft between the sending presynaptic neuron and the receiving postsynaptic neuron. When the neurotransmitter is a monoamine - like norepinephrine and serotonin - this process is called monoamine oxidase (MAO). As early as 1952 researchers at the Northwestern University Medical School in Chicago reported that iproniazid inhibited the oxidation of monoamines. This meant that iproniazid was a... 

In contrast, much is known about the catabolism of catecholamines. Adrenaline (epinephrine) released into the plasma to act as a classical hormone and noradrenaline (norepinephrine) from the parasympathetic nerves are substrates for two important enzymes monoamine oxidase (MAO) found in the mitochondria of sympathetic neurones and the more widely distributed catechol-O-methyl transferase (COMT). Noradrenaline (norepinephrine) undergoes re-uptake from the synaptic cleft by high-affrnity transporters and once within the neurone may be stored within vesicles for reuse or subjected to oxidative decarboxylation by MAO. Dopamine and serotonin are also substrates for MAO and are therefore catabolized in a similar fashion to adrenaline (epinephrine) and noradrenaline (norepinephrine), the final products being homo-vanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) respectively. 

Monoamine oxidase (MAO) inhibitors block the oxidative deamination of monoamines, i.e. norepinephrine and serotonin by inhibiting monoamine oxidase type A (MAO-A) and dopamine also by monoamine oxidase type B (MAO-B) inhibition, thereby increasing these neurotransmittors at their receptors in the brain and in the periphery. MAO-A... 

Monoamine oxidases (MAOs) are mitochondrial membrane enzymes. These flavin-dependent enzymes are responsible for the oxidative deamination of numerous endogenic and exogenic amines (norepinephrine, serotonin, dopamine, etc.). MAO A and B take part in the regulation of these amines in many organs, such as the brain. The essential physiological role of these amines, especially in the central nervous system, has motivated the search for inhibitors of their catabolism in order to enhance the synaptic concentration of neuroamines. 

Monoamine oxidase A (MAO A) acts selectively on the substrates norepinephrine and serotonin, whereas monoamine oxidase B (MAO B) preferentially affects phenylethylamine. Both MAO A and MAO B oxidize dopamine and tyramine. MAO A inhibition appears to be most relevant to the antidepressant effects of these drugs. Drugs that inhibit both MAO A and MAO B are called non-selective. The MAOI antidepressants currently available in the United States are nonselective inhibitors. Because tyramine can be metabolized by either MAO A or MAO B, drugs that selectively inhibit one of these enzymes but not the other do not require dietary... 

The first generation of antidepressants, MAO (monoamine oxidase) inhibitors, inhibited neurotransmitter degradation by inhibiting monoamine deoxidase, a flavin containing enzyme, found in the mitochondria of neurons and other cell types, that oxidatively deaminates naturally occurring sympathomimetic monoamines, such as norepinephrine, dopamine, and serotonin within the presynapse. In 1952, isoniazid and its isopropyl derivative, iproniazid (1), were developed for the treatment of tuberculosis, where it was subsequently found that these agents had a mood enhancing effect on... 

Monoamine oxidase inhibitors MAO is found in neural and other tissues, such as the gut and liver. In the neuron, this enzyme functions as a "safety valve" to oxidatively deaminate and inacti vate any excess neurotransmitter molecules (norepinephrine, dopamine, or serotonin) that may leak out of synaptic vesicles when the neuron is at rest. The MAO inhibitors2 may irreversibly or reversibly inactivate the enzyme, permitting neurotransmitter molecules to escape degradation and, therefore, to both accumu late within the presynaptic neuron and to leak into the synaptic space. This causes activation of norepinephrine and serotonin receptors, and may be responsible for the antidepressant action of these drugs. 

During clinical studies of iproniazid (201) in the treatment of tuberculosis it was found to have a mood-elevating effect. It was later found to be an inhibitor of monoamine oxidase (MAO), the enzyme which oxidatively deaminates such neurotransmitters as noradrenaline and serotonin, and it was tried in the treatment of depression in 1957. Other MAO inhibitors were introduced later, most of them being hydrazine derivatives. Heterocyclic examples include isocarboxazid (202) and nialamide (203). They are toxic and cause dangerous hypertensive crises if food with a high tyramine content is eaten, and on this account their use is limited. 

There are two enzymes capable of metabolizing catecholamines. The first is monoamine oxidase (MAO), a mitochondrial enzyme that oxidatively deaminates catecholamines, tyramine, serotonin, and histamine. MAO is further subclassified as either monoamine oxidase A, which metabolizes norepinephrine and is inhibited by tranylcypromine, and monoamine oxidase B, which metabolizes dopamine and is inhibited by 1-deprenyl. Catechol-O-methyltransferase (COMT), a soluble enzyme present mainly in the liver and kidney, is also found in postsynaptic neuronal elements. About 15% of norepinephrine is metabolized postsynaptically by COMT. 

Serotonin is metabolized by monoamine oxidase, and the intermediate product, 5-hydroxyindoleacetaldehyde, is further oxidized by aldehyde dehydrogenase to 5-hydroxyindoleacetic acid (5-HIAA). In humans consuming a normal diet, the excretion of 5-HIAA is a measure of serotonin synthesis. Therefore, the 24-hour excretion of 5-HIAA can be used as a diagnostic test for tumors that synthesize excessive quantities of serotonin, especially carcinoid tumor. A few foods (eg, bananas) contain large amounts of serotonin or its precursors and must be prohibited during such diagnostic tests. 

An example of a class of drugs that interrupt neurotransmitter degradation is the monoamine oxidase (MAO) inhibitors. MAO is a mitochondrial enzyme that exists in two forms (A and B). Its major role is to oxidize monoamines such as norepinephrine, serotonin, and dopamine by removing the amine grouping from the neurotransmitters. Under normal circumstances, MAO acts as a safety valve to degrade any excess transmitter molecules that may spill out of synaptic vesicles when the neuron is in a resting state. MAO inhibitors prevent this inactivation. In their presence, any neurotransmitter molecules that leak out of the synaptic vesicles survive to enter the synapse intact. Receptors are thus exposed to a greater amount of the neurotransmitter. 

Primary amines are oxidized in the body by monoamine oxidase (MAO). MAO converts the amine to an imine, which is hydrolyzed to yield an aldehyde and ammonia. One function of MAO is to regulate the levels of the neurotransmitters serotonin and norepinephrine. Monoamine oxidase inhibitors prevent the oxidation (and inactivation) of these neurotransmitters, thereby elevating mood. MAO inhibitors were the first antidepressants, but they are used sparingly now because of numerous side effects. 

The biological function of amine oxidases involves the oxidation of biogenic amines formed during normal biological processes. In mammals, the monoamine oxidases are involved in the control of the serotonin catecholamine ratios in the brain, which in turn influence sleep and EEG patterns, body temperature, and mental depression. Two groups of amine oxidases are involved in the oxidative deamination of naturally occurring amines as well as foreign compounds. 

Carbolines exert a variety of pharmacological effects, including sedation, catalepsy, inhibition of convulsion, hallucination, and inhibition of monoamine oxidases (MAO) and of monoamine uptake (104a,b). Extensively investigated was the inhibition of MAO by /3-carbolines, which is probably responsible for their antidepressant effects in man (5d). p-Caibolines inhibit the oxidative deamination of serotonin at micromolar... 

Monoamine oxidases (MAO-A and MAO-B) are mitochondrial enzymes that oxidatively deaminate endogenous biogenic amine neurotransmitters such as dopamine, serotonin, norepinephrine, and epinephrine. MAOs are like EMOs in that they catalyze the oxidation of drugs to produce drug metabolites that are identical in chemical structures to those formed by CYPs. Because the resulting structures are... 

Most tryptamine molecules are metabolized by the enzyme monoamine oxidase (MAO). MAO actually occurs in two different forms, MAO-A and MAO-B, which have preferences for different neurotransmitter molecules. MAO-A oxidizes the terminal amine of the tryptamines to an imine. This imine then undergoes nonenzymatic hydrolysis to an aldehyde that is subsequently converted to a carboxylic acid by a second enzyme, aldehyde dehydrogenase. The result is the conversion of the tryptamine into an acidic molecule, called an indole-3-acetic acid, which lacks psychoactivity. DMT is converted into indole acetic acid, whereas serotonin is converted into 5-hydroxyindole acetic acid (5-HIAA), and psilocin is converted into 4-hydroxy indole acetic acid. 

The hydroxylation of tryptophan produces 5-hydroxytryptophan, which can then be decarboxylated, catalyzed by tryptophan decarboxylase, a PALP-requiring enzyme, to 5-hydroxy tryptamine, also known as serotonin. Serotonin is an important compound in normal brain function and tranquility. Therefore, any disturbance of tryptophan metabolism via this pathway can lead to mental disturbances. Serotonin can be destroyed by the enzyme monoamine oxidase (a flavo protein), which catalyzes the formation of ammonia and 5-hydroxyindole acetaldehyde in an irreversible reaction. The aldehyde is rapidly oxidized enzymatically, utilizing NAD+ to form 5-hydroxy indoleacetate, which is then usually excreted. The formation and turnover of serotonin can be estimated by 5-hydroxy indoleacetate output in the urine. 

Monoamine oxidase (MAO) is another flavoenzyme that catalyzes the oxidation of carbon-nitrogen bonds. MAO has been studied extensively due to its physiological importance in the catabolism of amine neurotransmitters, such as norepinephrine, serotonin, and dopamine. There are two isozymes, MAO A and MAO B. The roles of both MAO A and MAO B are well documented in age-dependent neurodegenerative diseases and MAO inhibitors have been used to treat Parkinson s disease and depression. ... 

There are two enzymes capable of metabolizing catecholamines. The first is monoamine oxidase (MAO), a mitochondrial enzyme that oxidatively deaminates catecholamines, tyramine, serotonin, and histamine. MAO is further subclassified... 

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