Serotonin degrading enzyme

Monoamine oxidase A (MAOA) seems to be the principal serotonin degrading enzyme. The gene is located on chromosome Xpll [77]. Recent reports have shown that a low activity genetic variant of monoamine oxidase A (MAOA) is likely to be related to aggressive behavior, but only when paired with abusive experience in childhood. It also has been found that the low activity form of MAOA was associated with more adult symptoms of antisocial alcoholism than the high activity variant [113]. No studies related to autism have been carried out with this polymorphism (for more details see section 5 in Serotonergic innervations). 

While these functions can be a carried out by a single transporter isoform (e.g., the serotonin transporter, SERT) they may be split into separate processes carried out by distinct transporter subtypes, or in the case of acetylcholine, by a degrading enzyme. Termination of cholinergic neurotransmission is due to acetylcholinesterase which hydrolyses the ester bond to release choline and acetic acid. Reuptake of choline into the nerve cell is afforded by a high affinity transporter (CHT of the SLC5 gene family). 

Humans are a far bigger threat to lizards than they are to us. Lizards are generally slow moving and nocturnal, with few enemies other than humans. The venom is a complex mixture that contains serotonin, a neurotransmitter, but lacks many of the other protein-degrading enzymes. Clinical effects are minor unless you are small and receive a large dose. 

Both of these wonder drugs boost the synaptic efficacy of norepinephrine and serotonin, but they do so in quite different ways. Isoniazid blocks the action of the amine degrading enzyme monoamine oxidase, allowing the released amines to stay longer in the synaptic cleft (because they are... 

GABA analogs are used in the treatment of epilepsy and hypertension. Levels of GABA can also be increased by administering inhibitors of the GABA-degrading enzyme GABA aminotransferase. Another important neuro-transmitter, serotonin, is derived from tryptophan in a two-step pathway. 

Monoamine Oxidase Inhibitors (MAOIs). The MAOls work in a unique fashion by blocking the activity of an enzyme that degrades each of three key brain transmitters norepinephrine, dopamine, and serotonin. These widespread effects on several brain transmitter systems make the MAOls a potentially very effective class of medications for a variety of disorders. A few small studies have evaluated the usefulness of the MAOls in the treatment of BPD and found them moderately helpful for the impulsivity associated with this illness. Unfortunately, the requirements for strict dietary restrictions due to a risk of hypertensive crisis severely limit the usefulness of MAOls in the treatment of BPD. These restrictions are a particular concern when treating patients who have problems with impulsivity and are therefore likely to have difficulty maintaining the dietary regimen. For this reason, although they may theoretically be helpful, MAOls should only be used to treat BPD after other more easily tolerated medications have been tried and have failed. In the near future, so-called reversible MAOls that appear to avoid the need for diet restrictions may become available. If so, this will allow us to reconsider their use in the treatment of BPD. For more information regarding the use of MAOls, please refer to Chapter 3. 

Inhibition of the MAO-A enzyme for the treatment of depression is appealing because MAO-A is specifically responsible for the degradation of serotonin and norepinephrine. There was initial interest in clorgyline for treatment of adult depression and childhood ADHD (Potter et ah, 1982 Zametkin et ah, 1985). Clorgyline was found to be beneficial in a small, double-blind, crossover study for the treatment of ADHD in children, but adverse events associated with irreversibility resulted in the lack of an industry sponsor for further trials (Zametkin et ah, 1985). 

In depression, serotoninergic and/or noradrenergic neurotransmission is assumed to be deficient. One of the approaches to increase the availability of these neurotransmitters is to inhibit the activity of MAO, the enzyme involved in the degradation of serotonin and noradrenaline. Older drugs such as phenelzine and recently also moclobemide are representatives of this therapeutic approach used in some forms of depression. 

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. 

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. 

Catecholamines and serotonin also share the major mode of degradation. Both are substrates for monoamine oxidase (MAO), although one subtype of this enzyme (MAO A) has a preference for catecholamines, whereas the other (MAO... 

Drugs used to treat depressions that Inhibit the activity of the enzyme monoamine oxidase, which degrades the neurolransmitters of norepinephrine and serotonin. 

Wliile the cyclics block the uptake of amines, MAOls prc cnt the breakdown of the neurotransmitters (Cohen, 1997 Cooperrider, 1988 Meyer Quenzer, 2005). The enzyme monoamine oxidase metabolizes a variety of neurotransmitters, including norepinephrine and serotonin. MAOls inhibit this degradation process and thus enhance the availability of the transmitter within the neuron. Thii.s, the actions of the cyclics and MAOls each arc consistent u ith the hypothesis that decreased brain catecholamine activity causes depression and that these antidepressants (using different mechanisms) reverse this process by increasing catecholamine activity in the brain. 

Monoamine oxidase is the enzyme principally responsible for degradation of amine neurotransmitters (norepinephrine, epinephrine, serotonin, and dopamine). In general, monoamine oxidase inhibitors... 

Central Nervous System. Dopamine monooxygenase (DMO) is an enzyme that requires copper, as a cofactor and uses ascorbate as an electron donor. This enzyme catalyzes the conversion of dopamine to norepinephrine, the important neurotransmitter. There are soluble and membrane-bound forms of the enzyme, the latter being found in the chromaffin granules of the adrenal cortex. Monoamine oxidase, one of the numerous amine oxidases, is a copper-containing enzyme that catalyzes the degradation of serotonin in the brain and is also involved in the metabolism of the catecholamines. 

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