Monoamino oxidase

The main metabolic routes of dopamine and noradrenaline in the brain. COMT, Catechol O-methyltransferase MAO, monoamino oxidase DDC, dopa decarboxylase DBH, dopamine (3-hydroxylase 3-OMD, 3-methoxytyrosine Dopac, dihydroxyphenyl acetic acid. 

Biogenic amines in wine and fermented foods are formed primarily via the microbial decarboxylation of amino acids. Examples, such as histamine, tyramine, and phenylethylamine are toxic, especially in alcoholic beverages. Ethanol can inhibit the monoamino oxidase responsible for amine detoxification (Maynard and Schenker, 1996). Histamine can induce allergenic reactions in humans, such as rashes, edema, headaches, hypotension. Tyramine and phenylethylamine can cause hypertension and other symptoms related to the release of noradrenaline. 

In addition to the effects of the proinflammatory immune response on serotonin metabolism, other neurotransmitter systems, in particular the catecholaminergic system, are involved in depression, too. Although the relationship of immune activation and the lack of catecholaminergic neurotransmission has not been well studied, the increase of the monoamino-oxidase (MAO) activity, which leads to decreased noradrenergic neurotransmission, might be an indirect effect of the increased production of kynurenine and quinolinic acid (Schiepers et al., 2005). 

Although knowledge of subcellular distribution is still incomplete, it seems that I, receptors are limited to cell membranes (Piletz et al., 1991 Ernsberger et al., 1995) and, at least in some preparations, are possibly coupled to G proteins, while L receptors are primarily localized in mitochondria and associated with monoamino oxidases (Tesson et al., 1995). In addition, a recent study (Ems-berger et al., 1997) has shown that activation of I, receptors in PC 12 cells leads to the production of the second messenger diacylglycerol. 

Tesson, F., Limon-Boulez, I., Urban, P., Puype, M Vandekerckhove, J. et al., 1995. Localization of 12-imidazoline binding sites on monoamino oxidases. J. Biol. Chem. 270, 681-688. 

Gritsch S, Guccione S, Hoffmann RD, Cambria A, Raciti G, Langer T. A 3D QSAR study of monoamino oxidase B inhibitors using the chemical function based pharmacophore generation approach. J Enzyme Inhib 2001 16 199-215. 

Upon purification, the K -stimulated phosphatase activity is always copurified with the (K )-ATPase activity [63-65]. Mitochondrial markers, such as cytochrome c oxidase, succinate dehydrogenase, monoamino-oxidase, and the ribo-somal marker RNA are largely removed by the purification procedure. The same is true for the anion-sensitive ATPase and 5 nucleotidase activities, but some (Na — K )-ATPase activity is still present in highly purified (K" -I-H )-ATPase preparations. Purification is also characterised by a lowering of the K -insensitive Mg ATPase activity, but even in the purest preparations some Mg -ATPase activity (4% of (K -I- H )-ATPase activity) is still present. This may represent an impurity or an inherent property of the enzyme. 

Abuzzahab Sr, FS. Combination therapy monoamino oxidase inhibitors and bujM Opion HCI. 

Considering that oxoisoaporphine (7/f-dibenzo[rfe,/ ]quinolin-7-one ) have obtained the interest for its versatility in the synthesis of new derivatives in diverse medical action fields as its use in such parasitic diseases like Malaria [25] or Leishmania [26], the study of behavioral diseases as depression through compoimds that inhibit the human monoamino oxidase A (hMAO-A) or to reverse the depressed state in reserpinized animal testing, has been the first impulse to compile references of this type of alkaloid in the therapeutic scope under the observation of the neoplastic and psychiatric diseases. 

Sobarzo-Sanchez, E., Yanez Jato, M., Orallo Cambeiro, F., Uriarte Villares, E. Cano Rubio, E. (2009). Use of oxoisoaporphines and the derivatives thereof as selective inhibitors of monoamino oxidase A. PCTInt. Appl, WO 2009034216 A1 20090319. 

Molina, E., Sobarzo-Sanchez, E., Speck-Planche, A., Matos, M. J., Uriarte, E., Santana, L., Yanez, M. Orallo, F. (2012). Monoamino oxidase a an interesting pharmacological target for the development of multi-target QSAR. Mini Rev. Med. Chem., 72(10), 947-958. 

Brain uptake of [ C]harmine before and after esuprone treatment indicating expression of monoamino oxidase type A (MAO-A) (upper images) and after treatment with esuprone a marked inhibition [lower images)... 

Methyl - 4 - phenyl -1,2,3,6 - tetrahydropyridine (MPTP) is a frequently used animal model for Parkinson s disease. When injected into animals, MPTP is taken up by the cells in the substantia nigra where monoamino oxidase B (EC 1.4.3.4) converts it to l-methyl-4-phenylpyridinium ion (MPP ). This ion induces free radicals and duplicates many of the signs of Parkinson s disease in animals. In mice melatonin attenuated the resulting damage in the central nervous system (Acuna-Castroviejo et al. 1997). MPTP-induced neural lipid peroxidation was reduced to control levels when melatonin was co-administered with the herbicide. Neuronal loss and MPTP-induced reduction of tyrosine hydroxylase (EC 1.14.16.2) activity in neurones of the striatum were attenuated by melatonin. 

Depression is beyond any doubt the major psychiatric disorder that could affect every fifth individual at least once during their lifetime. There are several theories to explain development of depression including the role of noradrenaline, serotonine, acetylcholine, and dysregulation of neurotransmission. Therefore, antidepressants have many different and well-defined mechanisms of action such as enhancement of neurotransmitter synthesis, inhibition of neurotransmitter reuptake, monoamino oxidase (MAO) inhibition, antagonism of the activity of presynaptic inhibitory receptors, or increase in the activity of postsynaptic receptors. The reason for TDM in this class of drugs is that the metabolism and elimination show wide interindividual variability thus, when standard doses are applied the serum concentration is often out of the therapeutic range [27]. 

The second modified flavin of natural origin to be discovered was 8a-S-cysteinyl-FAD, the coenzyme of monoamino oxidase from liver and kidney outer mitochondrial membranes. Taking their departure from investigations of Yasunobu (8J) and Hellerman (SO), which indicated the presence of covalently bound flavin in preparations of this enzyme, Singer and his group (85, 185) isolated the flavinyl peptide by degradation of MAO with trypsin-chymotrypsin and identified cysteine as the amino acid residue bound next to the flavin moiety (184). The absorption spectrum of the flavin peptide from monoamino oxidase is readily differentiated from that of riboflavin by a hypsochromic shift of the second absorption band (360 nm, compare with 372 for riboflavin), in the neutral oxidized state (44, 184). It is similar to that of 8a-histidyl-riboflavin in the cationic state in that the band centered around 400 nm (abs. max. 375 nm, shoulder at 410 nm) is partially resolved. The fluorescence emission (4, 30) is only 10% of that of riboflavin, but oxidation with peracids raises it to 90% of riboflavin emission. 

Gartner, B., und P. Hemmerich Zur Propargylaminhemmung der Monoamino-oxidase Struktur des Inhibitor-Komplexes. Angew. Chem. 87, 137 (1975). 

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