Disease relevance of MAOB

• These data suggest that superoxide radicals are produced during the oxidation of MPTP by MAO-B and that the generation of H2O2 and .OH was secondary to the production of .O2-. It appears likely that the nigrostriatal toxicity of MPTP leading to Parkinson's disease-like syndrome may in part be mediated via these reactive oxygen species [1].
• Although haloperidol and its 1,2,3,6-tetrahydropyridine dehydration product were not substrates for purified bovine liver MAO-B, both compounds were biotransformed to the pyridinium product by rat liver microsomal preparations [2].
• The monoamine oxidase-B inhibitor L-deprenyl (Selegiline) is effective in treating Parkinson's disease and possibly Alzheimer's disease [3].
• Our data also suggest that iron is capable of increasing the cytotoxicity of dopamine merely by increasing its rate of oxidation and without intervention of the monoamine oxidase B enzyme and, hence, both phenomenons may occur independently from each other in rat pheochromocytoma PC12 [4].

High impact information on MAOB

• The chromaffin cells had MAO B exclusively and were inert to treatment with dexamethasone [5].
• The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to generate reactive oxygen species during its interaction with monoamine oxidase type B (MAO-B) [1].
• Catalase, a scavenger of hydrogen peroxide (H2O2), inhibited the DMPO-OH spin adduct formation in a dose-dependent manner, indicating that H2O2 is produced in the MAO-B catalyzed oxidation of MPTP [1].
• These data indicate that the formation of a ubiquitin conjugate is involved in the insertion of newly synthesized monoamine oxidase B into the outer membranes [6].
• Depletion of endogenous ubiquitin from the reticulocyte lysate with purified antibodies against this polypeptide inhibits the insertion of monoamine oxidase B, and this inhibition is relieved if ubiquitin is restored [6].

Biological context of MAOB

• Identification of imidazoline-receptor binding sites in cortex and medulla of the bovine adrenal gland. Colocalization with MAO-A and MAO-B [7].
• Each compound in the series inhibits both MAO A and MAO B competitively, and IC50 values for each compound were determined [8].
• Structure-activity relationships in the oxidation of benzylamine analogues by bovine liver mitochondrial monoamine oxidase B [9].
• The oxidative deamination of p-(N,N-dimethylamino)benzylamine and N-methyl-p-(N,N-dimethylamino)benzylamine by bovine liver monoamine oxidase B has been investigated by absorption spectral, steady-state, and stopped-flow kinetic studies [10].
• The kinetics of inactivation of mitochondrial monoamine oxidase type B (MAO-B) by a series of 18 stereoisomers of tertiary alpha-allenic amines have been investigated in detail [11].

Anatomical context of MAOB

• The corresponding kinetic values for this substrate in the retina and the choroid showed higher affinity for MAO A (Km 271 and 197 microM, respectively) than for MAO B (Km 861 and 404 microM, respectively) [12].
• A new series of thirty derivatives of 2-(5-methoxy-1-methylindolyl)alkylamines has been synthesized and the compounds assayed as inhibitors of MAO-A and MAO-B from bovine brain mitochondria [13].
• Monoamine oxidase B that has been synthesized by a reticulocyte lysate charged with bovine liver RNA will insert in a proteinase K-resistant form into isolated outer membranes from rat liver mitochondria [6].
• Comparison of the decreases in apparent levels of MAO-B in rat liver mitochondrial membranes that were calculated from changes in relative catalytic activities with A and B specific substrates or changes in sensitivity to A-form specific reversible and irreversible inhibitors, all showed good quantitative correlation [14].

Associations of MAOB with chemical compounds

• These results are discussed in terms of several mechanisms proposed for MAO catalysis and with previous structure-activity studies published with bovine liver MAO B [Walker, M. C., and Edmondson, D. E. (1994) Biochemistry 33, 7088-7098] [15].
• All the compounds tested were substrates for ox liver monoamine oxidase-B (MAO-B), producing an aldehyde that could act as a substrate for ox liver aldehyde dehydrogenase and H2O2 as a result of oxidative cleavage which also released glycinamide, although their Michaelis-Menten parameters differed markedly [16].
• [In a few samples we looked for but could not detect homovanillic acid or 3-methoxytyramine (O-methylated metabolites of DOPAC and DA respectively).] Deprenyl was about 44-72 times more potent an inhibitor of MAO than clorgyline when either DA or 5-HT was offered as substrate, suggesting that this MAO is of the MAOB type [17].
• The contribution of monoamine oxidase (MAO) A, MAO B and semicarbazide-sensitive amine oxidase (SSAO) to the metabolism of dopamine in the bovine retina was studied [12].
• The SSAO activities determined with 1 microM benzylamine were about half those determined for MAO-B [18].

Other interactions of MAOB

• The primary structure of bovine monoamine oxidase type A. Comparison with peptide sequences of bovine monoamine oxidase type B and other flavoenzymes [19].
• Ubiquitin is involved in the in vitro insertion of monoamine oxidase B into mitochondrial outer membranes [6].

Analytical, diagnostic and therapeutic context of MAOB

• Intrastriatal microdialysis in the rat with the corresponding 4-benzyl-1-methylpyridinium ion BMP+ for 60 min, however, causes nerve terminal destruction similar to that observed following a 15-min perfusion with the 1-methyl-4-phenylpyridinium ion MPP+, the monoamine oxidase B (MAO-B) generated metabolite derived from MPTP [20].
• Transmission electron microscopy of purified MAO B was performed using protein prepared by octyl glucoside extraction [21].
• Similarly, sucrose density gradient centrifugation of purified MAO B exhibited a direct correlation between enzyme activity and molecular mass of the MAO complexes [21].
• The quaternary structure and subunit composition of bovine liver monoamine oxidase B (MAO B) was investigated using size-exclusion chromatography, sucrose gradient centrifugation and electron microscopy [21].
• The secondary structure of human monoamine oxidase A and bovine monoamine oxidase B has been investigated by Fourier Transform Attenuated Total Reflection Spectroscopy (FTIR ATR) [22].

References