Rat Liver Monoamine Oxidase Research Articles

The sub-mitochondrial localization of monoamine oxidase in rat liver and brain

The large-amplitude swelling and phospholipase digestion techniques have been used to separate the outer- and the inner-membrane fractions of rat liver and brain mitochondria, and the distribution of monoamine oxidase (EC 1.4.3.4) in the fractions obtained has been compared with those of three other enzymes. The liquid nitrogen-temperature difference spectra of the reduced minus oxidized membrane fractions were also determined. The outer membrane fractions of liver mitochondria were rich in a cytochrome component with α-band maxima at 553 and 558 mμ but no evidence for such a cytochrome component in the outer membranes of brain mitochondria could be found. The results indicated that monoamine oxidase was at least partially located in the space between the outer and inner mitochondrial membranes. Penetration experiments showed that the inner of the two mitochondrial membranes was impermeable to a number of monoamine oxidase substrates.

Anion inhibition of monoamine oxidase

It was found that rat liver monoamine oxidase is inhibited by various anions and that the degree of inhibition depends on which of two substrates, serotonin or tyramine, is used to test the monoamine oxidase activity. In addition, the inhibition by anions is affected by pH and temperature in ways that differ with the two substrates: for example, with rising temperatures inhibition of tyramine deamination by salts increases while inhibition of serotonin deamination decreases. The differential inhibition of MAO by anions suggests the existence of more than one active site or more than one enzyme subunit in rat liver monoamine oxidase. The relative substrate specificity of the inhibitions by anions suggests that there might exist other substrate-specific inhibitors.

Studies on monoamine oxidase inhibitors. IV. On the mode of nonspecific inhibitory action

Inhibitory action of several compounds on rat liver monoamine oxidase was investigated according to Ferguson's rule and Mullins' hypothesis. Aliphatic primary alcohols, their acetates, aralkyl alcohols, phenethylamines, and piperidinoacetophenones decreased monoamine oxidase activity to about one-half of non-treated preparation at the concentration giving thermodynamic activities of 10-1 to 10-2. These results suggest that these compounds might be classified as drugs having a "physical toxicitiy" and affected monoamine oxidase by their physicochemical properties. Volume fractions of alcohols were also calculated and a theoretical curve calculated from δblo=11.5 and XV=6.7 fltted the experimental values.

Studies on monoamine oxidase inhibitors. II. Action of phenethylamine derivatives

The dose-response relationships of phenethylamine derivatives and pentylamine as substrate or inhibitor of rat liver monoamine oxidase were investigated. Increased concentration of tyramine increased the rate of oxidative deamination which later decreased. This bell-shaped dose-response curve of tyramine agreed fairly well with the theoretical curve calculated from eq. (3). Dissociation constants of tyramine-monoamine oxidase complex were estimated to be Km=4.5×10-4M as a substrate and KI'=1.0×10-2M as an inhibitor. Phenethylamine, 4-methoxyphenethylamine, and pentylamine were more or less active as substrates of monoamine oxidase, but also inhibited monoamine oxidase at higher concentration partially non-competitively. From these results, it is concluded that these amines act both as a substrate and an inhibitor, and the dose-response curves of these amines can be represented by eq. (3).

Inhibition of monoamine oxidase action on kynuramine by substrate amines and stereoisomeric α-methyl amines

Kynuramine oxidation by rat liver monoamine oxidase was inhibited by dopamine, norepinephrine, phenethylamine, phenylbutylamine, serotonin, or tyramine. Although these were all substrates for the enzyme preparation, there was no consistent relationship between degree of inhibition and efficacy as substrate. The α-methyl analogues of dopamine, norepinephrine, phenethylamine, tyramine, or 4-chlorophenethylamine also inhibited kynuramine oxidation. The degree of inhibition by the α-methyl compounds was, in most cases, less than that by the parent compounds. Inhibition of MAO by α-methyl amines (amphetamine, 2, 4-dichloroamphetamine, 4-chloro-N-methyl-amphetamine, or 3, 4-dichloroamphetamine) was greater with the dextrorotatory isomers than with the levorotatory isomers.

The mechanism of the irreversible inhibition of rat liver monoamine oxidase by iproniazid (Marsilid)

The mechanism of the irreversible inhibition of rat liver monoamine oxidase by iproniazid (Marsilid)

Action of rat liver monoamine oxidase on multiple substrates

It is concluded that tyramine, tryptamine, phenylethylamine, and probably i-amylamine are attacked by monoamine oxidase of washed rat liver mitochondrial fraction at the same reactive center(s) of the enzyme. In a mixture, each amine at saturation is oxidized relative to its affinity for the enzyme. Relative affinities manifest themselves at microgram concentrations of the substrate.