Monoamine oxidase deficiency

Genetic disorders (not included above) tyrosine hydroxylase deficiency dopa-responsive dystonia dihydropteridine reductase deficiency aromatic L-amino acid decarboxylase deficiency Menkes disease monoamine oxidase deficiency. 

Vanadium. Vanadium is essential in rats and chicks (85,156). Estimated human intake is less than 4 mg/d. In animals, deficiency results in impaired growth, reproduction, and Hpid metaboHsm (157), and altered thyroid peroxidase activities (112). The levels of coen2yme A and coen2yme Q q in rats are reduced and monoamine oxidase activity is increased when rats are given excess vanadium (157). Vanadium may play a role in the regulation of (NaK)—ATPase, phosphoryl transferases, adenylate cyclase, and protein kinases (112). 

After reuptake into the cytosol, some noradrenaline may be taken up into the storage vesicles by the vesicular transporter and stored in the vesicles for subsequent release (see above). However, it is thought that the majority is broken down within the cytosol of the nerve terminal by monoamine oxidase (MAO ECl.4.3.4). A second degradative enzyme, catechol-O-methyl transferase (COMT EC2.1.1.6), is found mostly in nonneuronal tissues, such as smooth muscle, endothelial cells or glia. The metabolic pathway for noradrenaline follows a complex sequence of alternatives because the metabolic product of each of these enzymes can act as a substrate for the other (Fig 8.8). This could enable one of these enzymes to compensate for a deficiency in the other to some extent. 

Lenders, JWM, Eisenhofer, G, Abeling, NGGM et al. (1996) Specific genetic deficiencies of the A and B isoenzimes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes. J. Clin. Invest. 97 1010-1019. 

This condition is cansed by a deficiency of one or more of the monoamine nenrotransmitters in the brain (e.g. noradrenaline, dopamine, 5-hydroxytryptamine). One means of increasing the concentration of the neurotransmitters is to inhibit one of the enzymes that degrade the neurotransmitter in the brain. For the monoamines, a key degradative enzyme is monoamine oxidase, which catalyses the reaction... 

The 1960 s and 1970 s saw several other hypotheses proposed and dis-proven. The monoamine oxidase (MAO) deficiency hypothesis was based on the observation of diminished activity of platelet MAO-B in schizophrenia, although this was likely to be an artifact of drug treatment and the small deficits could not, in any case, account for changes in monoamine transmitters. Other hypotheses relating to, among other transmitter molecules, noradrenaline and enkephalin/endorphin have also been proposed. Each of these have had propo-... 

Burnet H, Bevengut M, Chakri F, Bou-Flores C, Coulon P, Gaytan S, Pasaro R, Hilaire G (2001) Altered respiratory activity and respiratory regulations in adult monoamine oxidase A-deficient mice. J Neurosci 21 5212-5221... 

This was put forward in 1965 by J. Schildkraut and states that some, if not all, depressions are the consequence of an absolute or relative deficiency of catecholamines, particularly norepinephrine, at functionally important adrenergic receptor sites in the brain (Schildkraut, 1965, p. 509). The evidence brought forward in support of this hypothesis was impressive (Table 4.2) because it covered both clinical and multifarious pharmacological findings. The antidepressant effect of imipramine and of the monoamine oxidase (MAO) inhibitors was attributed to the fact that these medicaments bring about an increased supply of functionally available catecholamines at the synapse ... 

FIGURE 5 — 15. Monoamine oxidase inhibitors act as antidepressants, since they block the enzyme MAO from destroying monoamine neurotransmitters, thus allowing them to accumulate. This accumulation theoretically reverses the prior neurotransmitter deficiency (see Fig. 5—14) and according to the monoamine hypothesis, relieves depression by returning the monoamine neuron to the normal state. 

DIAMINE OXIDASE INHIBITORS act on the non-selective enzyme diamine oxidase (histaminase), which has as substrate such diverse substances as histamine, cadaverine and putrescine. As with the monoamine-oxidase enzyme, an intermediate complex is formed to yield the aldehyde, and this is then oxidized. The enzyme has been studied in relation to histamine metabolism, and is found to be released in certain circumstances from eosinophils and other tissues, and can be used as a marker in thyroid and ovarian carcinoma. Blood levels are raised in pregnancy, and heparin raises these levels. Amounts of the enzyme are high in the intestinal mucosa, liver and kidney of most species, A preparation of the enzyme itself (Torantil ) was once available for use in therapeutics for conditions in which a deficiency of histamine was implicated. 

Somewhat different results were reported from other laboratories n-3 fatty acid deficiency in rats caused a decrease in dopamine level and D2-receptor density in the frontal cortex as well as a decrease in serotonin receptor density (Delion, 1994,1996), whereas fish oil increased the dopamine level (Chalon, 1998). A decrease in the dopamine release from the frontal cortex was also detected by the microdialysis method after thyramine stimulation but not after KCl stimulation (Zimmer, 1998, 2000). In aged rats, however, the monoamine level was not affected, whereas monoamine oxidase activity was decreased during n-3 fatty acid deficiency (Delion, 1997). 

Cases O, Vitalis T, Seif 1, De Maeyer E, Sotelo C, Caspar P (1996) Lack of barrels in the somatosensory cortex of monoamine oxidase A-deficient mice role of a serotonin excess during the critical period. Neuron 16 297-307. 

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