Evidence of a coupled mechanism between monoamine oxidase and peroxidase in the metabolism of tyramine by rat intestinal mitochondria

Article abstract of DOI:10.1016/S0006-2952(97)00379-1

The relationship between monoamine oxidase (EC 1.4.3.4; MAO) and peroxidase (EC 1.11.1.7; POD) in the metabolism of tyramine was investigated using the crude mitochondrial fraction of rat intestine. When tyramine was incubated with mitochondria, the formation of the peroxidase-catalysed oxidation product, 2,2'-dihydroxy-5,5'-bis(ethylamino)diphenyl (dityramine), identified by mass spectrometric analysis, was monitored spectrophotometrically. After an initial lag time, the formation rate of dityramine was linear up to 2 hr, amounting to 17 nmol x hr^-1 x mg protein^-1. A similar value was found for the oxidative deamination of tyramine catalysed by intestinal MAO. Either 10^-3 M clorgyline or 10^-3 M NaCN suppressed this reaction by completely inhibiting MAO or POD, respectively. In the former case, however, addition of H₂O₂ to the incubation mixture promptly started the reaction. Selective inhibition of MAO-A and MAO-B was achieved with 3 x 10^-7 M clorgyline and 3 x 10^-7 M deprenyl, respectively, and the formation rate of dityramine decreased in a corresponding manner. Preincubation with histamine or spermidine reduced the lag time without affecting the steady-state reaction rate. Higher levels of dityramine were also detected in vivo in rat intestine after oral administration of tyramine. These results indicate that the peroxidase-dependent metabolism of tyramine in the gut may be driven by H₂O₂ produced by MAO activities and that MAO-A is mainly responsible for this process, as well as for the oxidative deamination of tyramine.