Monoamine oxidase serotonin catabolism

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. 

Serotonin is an indolamine neurotransmitter, derived from the amino acid L-tryptophan. Tryptophan is converted to 5-hydroxytryptophan (5-HTP) by tryptophan hydroxylase. 5-HTP is converted to 5-hydroxytryptamine (serotonin, 5-HT) by aromatic amino acid decarboxylase. In the pineal gland, 5-HT may be further converted to /V-acetyl serotonin by 5-HT /V-acetyltransferase and then to melatonin by 5-hyroxyindole-O-methyltransferase. 5-HT is catabolized by monoamine oxidase, and the primary end metabolite is 5-hydroxyindoleacetic acid (5-HIAA). 

Monoamine oxidase exists in the human body in two molecular forms, known as type A and type B. Each of these isozymes has selective substrate and inhibitor characteristics. Neurotransmitter amines, such as norepinephrine and serotonin, are preferentially metabolized by MAO-A in the brain. MAO-B is more likely to be involved in the catabolism of human brain dopamine, although dopamine is also a substrate for 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 inhibitors. The monoamine oxidase inhibitors (MAOIs) inhibit the intracellular catabolic enzyme monoamine oxidase. There are two types of monoamine oxidase MAO-A and MAO-B, both of which metabolize tyramine and dopamine. In addition, MAO-A preferentially metabolizes norepinephrine, epinephrine, and serotonin, and MAO-B preferentially metabolizes phenylethylamine (an endogenous amphetamine-like substance) and N-methylhistamine (Ernst, 1996). Some MAOIs are selective for A or B and some are nonselective (mixed). In addition, irreversible MAOIs (e.g., phenelzine, tranylcypromine) are more susceptible to the cheese effect than are the reversible agents (e.g., moclobemide). 

Monoamine Oxidase (MAO) Inhibitors. Inhibitors of the catabolic enzyme MAO increase both catecholamine and serotonin brain levels, which in turn produce significant and prolonged decrease in REM sleep. This is especially the case with phenelzine and nialamide nonselective MAO inhibitors and less pronounced with the reversible MAO-A inhibitor moclobemide. In normal subjects, moclobemide reduces REM sleep period during the first night, but by the third night, REM sleep returns to normal levels (37). 

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. ... 

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