Monoamine oxidase distribution

Monoamine Oxidases and their Inhibitors. Table 3 Distribution and proportions of the A and B forms of monoamine oxidases in adult rat and human tissues... 

Bogdanski, D.F. Weissbach, H. and Udenfriend, S. The distribution of serotonin, 5-hydroxytryptophan decarboxylase, and monoamine oxidase in brain. J Neurochem 1 272-278, 1957. 

FIGURE 29-2. Levodopa absorption and metabolism. Levodopa is absorbed in the small intestine and is distributed into the plasma and brain compartments by an active transport mechanism. Levodopa is metabolized by dopa decarboxylase, monoamine oxidase, and catechol-O-methyltransferase. Carbidopa does not cross the blood-brain barrier. Large, neutral amino acids in food compete with levodopa for intestinal absorption (transport across gut endothelium to plasma). They also compete for transport across the brain (plasma compartment to brain compartment). Food and anticholinergics delay gastric emptying resulting in levodopa degradation in the stomach and a decreased amount of levodopa absorbed. If the interaction becomes a problem, administer levodopa 30 minutes before or 60 minutes after meals. 

Kitahama, K, Sakai, K., Tago, H. et al. (1984). Monoamine oxidase-containing neurons in the cat hypothalamus distribution and ascending projection to the cerebral cortex. Brain Res. 324, 155-9. 

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. 

MAOIs act by mitigating the actions of monoamine oxidase in the neuron and increasing monoamine content. There are two forms of monoamine oxidase. MAO-A is present in both dopamine and norepinephrine neurons and is found primarily in the brain, gut, placenta, and liver its primary substrates are norepinephrine, epinephrine, and serotonin. MAO-B is found primarily in serotonergic and histaminergic neurons and is distributed in the brain, liver, and platelets. MAO-B acts primarily on tyramine, phenylethylamine, and benzylamine. Both MAO-A and -B metabolize tryptamine and dopamine. 

Amine oxidation. As well as the microsomal enzymes involved in the oxidation of amines, there are a number of other amine oxidase enzymes, which have a different subcellular distribution. The most important are the monoamine oxidases and the diamine oxidases. The monoamine oxidases are located in the mitochondria within the cell and are found in the liver and also other organs such as the heart and central nervous system and in vascular tissue. They are a group of flavoprotein enzymes with overlapping substrate specificities. Although primarily of importance in the metabolism of endogenous compounds such as 5-hydroxy try pt-amine, they may be involved in the metabolism of foreign compounds. 

DISTRIBUTION OF MONOAMINE OXIDASES A AND B mRNAs IN THE RAT BRAIN BY IN SITU HYBRIDIZATION... 

Monoamine oxidases catalyze oxidative deamination of many primary, secondary, and tertiary amines. They have a wide tissue distribution including brain, liver, and intestine. A variety of endogenous amines, such as catecholamines, and pharmacological substances are metabolized. The products of primary amines are the corresponding aldehydes, ammonia, and hydrogen peroxide. 

Disposition in the Body. Rapidly metabolised before reaching the systemic circulation and therefore ineffective after oral administration poorly absorbed after subcutaneous injection widely distributed throughout the body. The principal metabolic reaction is 0-methylation catalysed by catechol-O-methyltrans-ferase to form normetanephrine this is followed by oxidative deamination catalysed by monoamine oxidase, to form 4-hydroxy-3-methoxymandelic aldehyde which is converted to 4-hydroxy-3-methoxymandelic acid (vanillylmandelic acid) and to... 

Monoamine oxidase inhibitors are rapidly and completely absorbed orally reaching peak blood levels within 2 h. Monoamine oxidase inhibitors are acety-lated in the liver to many active and inactive metabolites. The volume of distribution is estimated to range from 1 to 41 kg The inactive metabolites are excreted by the kidneys. The elimination half-lives of monoamine oxidase inhibitor parent compounds range from 15 min to 3.5 h. The biologic half-life often significantly exceeds the elimination half-life. 

Itzhak, Y., Stein, I., Zhang, S.H., Kassim, C.O., Cristante, D., 1991. Binding of sigma-ligands to C57BL/6 mouse brain membranes effects of monoamine oxidase inhibitors and subcellular distribution studies suggest the existence of sigma-receptor subtypes. J. Pharmacol. Exp. Ther. 257, 141-148. 

McCaman, R. E., Rodriguez de Lores Arnaiz, G. and De Robertis, E. (1965) Species differences in subcellular distribution of choline acetylase in the CNS. A study of choline acetylase, acetylcholinesterase, 5-hydroxytryptophan decarboxylase, and monoamine oxidase in four species. J. Neurochem., 12, 927-935. 

An explanation of the mode of action of the monoamine oxidase inhibitors in terms of their intervention in central transmission processes is difficult for several reasons. Monoamine oxidase is widely distributed in the body and some of the consequences of its inhibition may arise peripherally in the brain the enzyme participates in the inactivation of at least three substances (noradrenaline, dopamine and 5-hydroxytryptamine). Not all monoamine oxidase inhibitors have antidepressant activity but those that have may owe at least part of their activity to an action other than enzyme inhibition. 

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. 

A and B are composed of two subunits, each of which contains an FAD molecule Monoamine oxidase is located in the outer mitochondrial membrane and is distributed peripherally in neuronal and nonneuronal tissues (liver, intestines) as well as in the central nervous system. Few organs have exclusively one form of the enzyme. Thus, in human placenta over 99% of the enzyme is of the A type while platelets lymphocytes... 

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