Mitochondrial Monoamine Oxidase

The structure of the covalent adduct formed by the interaction of 3-dimethylamino-1-propyne and the flavine of mitochondrial amine oxidase

“…This corresponds to a ratio of 2.3-2.8 mol of inhibitor per mol of cysteinylflavine. Although the determination of flavine in the study of Chuang et al (1974) was an approximation based on bleaching of the enzyme with dithionite and an assumed molar absorptivity, rather than analysis for cysteinylflavine as in the present study, this would not account for the discrepancy in the amount of incorporated label. A more plausible explanation is that the slow oxidation of compound I gives rise to product(s) which combine nonspecifically with MAO itself, as well as with protein impurities.…”

“…Figure 2 shows the spectral changes occurring during the inactivation of MAO with compound I. As in the case of pargyline (Chuang et al, 1974), concurrently with disappearance of the long wavelength absorption of the enzyme in the 450-500-nm region, absorbance at 410 nm rises as inactivation develops. Based on cysteinylflavine content, the molar absorptivity of the inhibited species is 6410 28000 (average value from three experiments).…”

“…In previous studies with [7-l4C]pargyline (Chuang et al, 1974) it was found that exactly 1 mol of labeled inhibitor became bound to MAO on complete inactivation. With the inhibitor used in the present study a considerably higher ratio of inhibitor binding per mole of enzyme was observed.…”

“…Inactivation of MAO from pig liver mitochondria by pargyline has been studied by Oreland et al (1 973). Recently, Chuang et al (1974) reported that the inhibition of kidney MAO by pargyline is accompanied by disappearance of the 455-nm band of the flavoquinone and the appearance of a new band at 410 nm. This fact and the observation that [7-14C]pargyline is recovered in the flavine peptide fraction after proteolytic digestion were taken as ev-114 BIOCHEMISTRY.…”

Multitarget Biological Profiling of New Naphthoquinone and Anthraquinone-Based Derivatives for the Treatment of Alzheimer’s Disease

“…For higher coincubation times (up to 2 h) the mechanism apparently turned noncompetitive, with the K i increasing about 20-fold. This change could be ascribed to the formation of a covalent complex with the N5 of flavin, 48 due to the presence of the chlorine leaving group. Indeed, a time course of absorption of 4-hydroxyquinoline at 316 nm revealed that the enzymatic activity was still present even after 3 h in the presence of 10 nM 2 (Figure 3).…”