Human monoamine oxidases

Binda C, Hubalek F, Li M, Edmondson DE, Mattevi A. Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane. FEBS Lett 2004 564 225-8. 

Saura, J, Bleuel, Z, Ulrich, J, Mendelowitsch, A, Chen, K, Shih, JC, Malherbe, P, Da Prada, M and Richards, JG (1996) Molecular neuroanatomy of human monoamine oxidases A and B revealed by quantitative enz5mie radioautoradiography and in situ hybridization histochemistry. Neurosci. 70 755-774. 

Binda C, Newton-Vinson P, Hubalek F, et al. Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders. Nat Struct Biol 2002 9(l) 22-26. 

Binda C, Wang J, Pisani L, Caccia C, Carotti A, Salvati P, Edmondson DE, Mattevi A. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors sa-finamide and coumarin analogs. J. Med. Chem. 2007 50 5848-5852. 

Grimsby, J., Chen, K., Wang, L.-J., Lan, N.C. and Shih, J.C. (1991) Human monoamine oxidase A and B genes exhibit identical exon-intron organization. Proc. Natl. Acad. Sci. USA 88 3637-3641. 

Chimenti, R, Bolasco, A., Secci, D., Chimenti, P., Granese, A., Carradori, S., Yinez, M., OraUo, R, Ortuso, R and Alcaro, S. 2010. Investigations on the 2-thiazolylhydrazyne scaffold Synthesis and molecular modeling of selective human monoamine oxidase inhibitors. Bioorg. Med. Chem. 18 5715-5723. 

Herraiz T, Chaparro C (2005) Human monoamine oxidase is inhibited by tobacco smoke P-carboline alkaloids act as potent and reversible inhibitors. Biochem Biophys Res Commun 326 378-386... 

Herraiz T, Chaparro C (2006) Human monoamine oxidase enzyme inhibition by coffee and P-carbolines norharman and harman isolated frran coffee. Life Sci 78 795-802... 

Herraiz T, Gonzalez D, Ancm-Azpilicueta C, Aran VJ, Guillen H (2010) Beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food Chem Toxicol 48 839-845... 

Seed, D. Carradori, S. Bolasco, A. Chimenti, P Yanez, M. Ortuso, K Alcaro, S. Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives. Eur. J. Med. Chem. 2011, 46, 4846 852. 

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). 

Copper is one of the twenty-seven elements known to be essential to humans (69—72) (see Mineral nutrients). The daily recommended requirement for humans is 2.5—5.0 mg (73). Copper is probably second only to iron as an oxidation catalyst and oxygen carrier in humans (74). It is present in many proteins, such as hemocyanin [9013-32-3] galactose oxidase [9028-79-9] ceruloplasmin [9031 -37-2] dopamine -hydroxylase, monoamine oxidase [9001-66-5] superoxide dismutase [9054-89-17, and phenolase (75,76). Copper aids in photosynthesis and other oxidative processes in plants. 

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... 

Medvedev AE, Veselovsky AV, Shvedov VI, Tikhonova OV, Moskvitina TA, Fedotova OA, et al. Inhibition of monoamine oxidase by pirlindole analogues 3D-QSAR and CoMFA analysis. / Chem Inf Comput Sci 1998 38 1137-44. Miller JR, Edmondson DE. Structure-activity relationships in the oxidation of para-substituted benzylamine analogues by recombinant human liver monoamine oxidase A. Biochemistry 1999 38 13670-83. 

Binda C, Li M, Hubalek E, Restelli N, Edmondson DE, Mattevi A. Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures. Proc Natl Acad Sci USA 2003 100 9750-5. 

Monoamine oxidase exists in two forms, MAOa and MAOb. The former is more active against NA and 5-HT than it is against DA, which is a substrate for both, even though, like S-phenylethylamine, it is more affected by MAOb. H seems likely that MAOb is the dominant enzyme in human brain and inhibitors of it, such as selegiline, have some value in the treatment of Parkinson s disease by prolonging the action of the remaining endogenous DA as well as that formed from administered levodopa. 

CYP. cytochrome P450 isoenzyme HIV, human immunodeficiency vims INR, International Normalized Ratio LFTs, liver function tests MAOI, monoamine oxidase inhibitor PT, prothrombin time TCA, tricyclic antidepressant. 

Once returned to the presynaptic terminal, dopamine is repackaged into synaptic vesicles via the vesicular monoamine transporter (VMAT) or metabolized to dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO). Two alternative pathways are available for dopamine catabolism in the synapse, depending on whether the first step is catalyzed by MAO or catechol-O-methyltransferase (COMT). Thus, dopamine can be either deaminated to 3,4-dihydroxyphenylacetic acid (DOPAC) or methylated to 3-methoxytyramine (3-MT). In turn, deamination of 3-MT and methylation of DOPAC leads to homovanillic acid (HVA). In humans, cerebrospinal fluid levels of HVA have been used as a proxy for levels of dopaminergic activity within the brain (Stanley et al. 1985). 

Bach AW, Lan NC, Johnson DL, et al. cDNA cloning of human liver monoamine oxidase A and B molecular basis of differences in enzymatic properties. Proc Natl Acad Sci USA 1988 85(13) 4934—4938. 

Urine catecholamines may also serve as biomarkers of disulfoton exposure. No human data are available to support this, but limited animal data provide some evidence of this. Disulfoton exposure caused a 173% and 313% increase in urinary noradrenaline and adrenaline levels in female rats, respectively, within 72 hours of exposure (Brzezinski 1969). The major metabolite of catecholamine metabolism, HMMA, was also detected in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1971). Because organophosphates other than disulfoton can cause an accumulation of acetylcholine at nerve synapses, these chemical compounds may also cause a release of catecholamines from the adrenals and the nervous system. In addition, increased blood and urine catecholamines can be associated with overstimulation of the adrenal medulla and/or the sympathetic neurons by excitement/stress or sympathomimetic drugs, and other chemical compounds such as reserpine, carbon tetrachloride, carbon disulfide, DDT, and monoamine oxidase inhibitors (MAO) inhibitors (Brzezinski 1969). For these reasons, a change in catecholamine levels is not a specific indicator of disulfoton exposure. 

Bonson KR, Buckholtz JW, Murphy DL. (1996). Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology. 14(6) 425-36, Bonson KR, Murphy DL. (1996). Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors, or lithium. Behav Brain Res. 73(1-2) 229-33. 

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