Dopamine oxidation and its inhibition by (-)-deprenyl in man.
Dopamine is predominantly oxidized by a (-)-deprenyl sensitive form of MAO in the human striatum, and (-)-deprenyl, acting at some suitably low selective inhibitory concentration may, therefore, be of benefit in Parkinson's disease. 10(-6)M was the most effective (-)-deprenyl concentration in vitro for discriminating between the inhibition of MAO A and B. The correlation between the A/B ratio present in different human brain regions and the sensitivity of dopamine oxidation to 10(-6)M deprenyl was 0.84 (p<0.001). This suggests that all dopamine oxidation can be accounted for by the joint contribution of MAO A and B and that it is unnecessary to postulate a special form of the enzyme which metabolizes dopamine. In the brain, the striatum has the highest proportion of MAO B, and in several cortical regions, relatively more dopamine is oxidized by MAO A. In other human tissues also the deprenyl sensitivity of dopamine oxidation correlated with the known A/B ratio, the placenta, lung and jejeunum having the lowest sensitivity and being the richest in MAO A. Km values for dopamine for MAO A and B are similar, 130 and 140 uM respectively, so that the proportion oxidized by the two forms should not vary with substrate concentration.
D001792:Blood Platelets / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D012642:Selegiline / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism
D009419:Nerve Tissue Proteins; D010627:Phenethylamines; D012642:Selegiline; D012701:Serotonin; D004298:Dopamine