Monoamine oxidase, isoforms

B.M.H. Youdim, Y.S. Bakhle, Monoamine oxidase isoforms and inhibitors in Parkinson s disease and depressive illness, Br. J. Pharmacol. 147 (2006) 5287-5296. 

Chimenti F, Fioravanti R, Bolasco A et al (2007) Monoamine oxidase isoform-dependent tautomeric influence in the recognition of 3,5-diaryl pyrazole inhibitors. J Med Chem 50 425 28... 

The norepinephrine transporter (NET) and the vesicular monoamine transporter (VMAT) are presynaptic components of the sympathetic neurons. NET is a Na+ /Cl -dependent transport protein and responsible for the neurotransmitter uptake from the synaptic cleft into the cytoplasm of the neurons. This transport process, called uptake-1, reduces the amount and, thus, the effect of NE released into the synaptic cleft. NE is stored in the cytoplasm of the neurons in specialized vesicles by the H+-dependent transport protein VMAT. Two isoforms VMAT1 and VMAT2, are known. VMAT is localized in the vesicle membranes, and the vesicular storage protects NE from metabolism by monoamine oxidase (MAO), which is localized on the surface membrane of the mitochondria. Vice versa, nerve depolarisation causes NE release from the vesicles into the synaptic cleft by Ca+-mediated exocytose (Fig. 12) [79,132-136],... 

Two distinct isoforms of monoamine oxidase, the A and B isoforms, have been identified. 

The HPLC method described here allows the assay of both isoforms in the same run by using 5-hydroxytryptamine and 3-methoxy-4-hydroxybenzyl-amine as highly selective substrates for the A and B isoforms, respectively. The product of 5-hydroxytryptamine that is quantitated is 5-hydroxyindole-2-carboxylic acid, which is obtained by including aldehyde dehydrogenase in the assay mixture to oxidize the intermediate aldehyde. The product of monoamine oxidase B is 3-methoxy-4-hydroxybenzaldehyde. The internal standards used are 5-hydroxyindole-2-carboxylic acid and 3,4-dihydroxyben-zoic acid. 

The main varieties of adverse effects attributed to cimetidine relate to its antiandrogenic properties and its actions in sufficient concentrations on the central nervous system. There is also a spectrum of drug interactions, mainly attributable to inhibition of hepatic CYP isoforms, but they only have clinical consequences under special circumstances. Occasional adverse effects, which are generally minor, include bradycardia and conduction defects, thrombocytopenia, neutropenia, interstitial nephritis, mild hepatic dysfunction, and headache. Intestinal infection due to loss of the gastric acid barrier also occurs, and myalgia, fever, monoamine oxidase-Uke interactions, and neuropathies have been well documented occasionally. Allergic reactions, such as bronchospasm, have rarely been described. Anaphylaxis with recurrence on rechallenge is on record, as are asthma and skin effects. 

Monoamine Oxidases (MAO) There are two MAO isoforms, MAO A and MAO B, both of which are flavoen-zymes that oxidize a wide array of neurotransmitter amines. However, they can also biotransform some xenobiotics. Both MAO isoforms consist of approximately 520 amino acid residues and share approximately 70% sequence identity. Their molecular weights are about 58K Daltons. Both isoforms are expressed in most tissues, though not necessarily in equivalent amounts. More MAO is found in liver and placenta, and least in the spleen. Actually MAO-B is... 

Monoamine oxidase (MAO) is an enzyme present in the outer mitochondrial membrane of neuronal and non-neuronal cells. Two isoforms of MAO exist MAO-A and MAO-B. The MAO enzymes are responsible for the oxidative deamination of endogenous and xenobiotic amines, and have different substrate preferences, inhibitor specificities, and tissue distributions. MAO inhibition allows endogenous and exogenous substrates to accumulate, and may thereby alter the dynamics of regular monoamine transmitters, such as norepinephrine, serotonin, and dopamine. Specifically, MAO-A deaminates serotonin, norepinephrine, and dopamine, and MAO-B deaminates dopamine, [3-phenylethylamine, and benzylamine. In the human brain, about 75% of MAO is of the B subtype. Hence, the primary effect of MAO inhibitors (MAOIs) is to increase the availability of these neurotransmitters at the nerve terminal. 

Monoamine oxidases (MAOs) are mitochondrial outer membrane-bound flavoenzymes that catalyze the degradation of biogenic amines, more specifically the oxidative deamination of several important neurotransmitters, including 5-hydroxytiyptamine (5-HT) (or serotonin), histamine, and the catecholamines dopamine, noradrenaline, and adrenaline. There are two isoforms... 

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