Outer mitochondrial membrane flavoenzymes — degrade biogenic amines via oxidative deamination → aldehyde intermediates → carboxylic acids (via ALDH). MAO-A: serotonin, norepinephrine, dopamine (high affinity) — broad tissue distribution. MAO-B: dopamine, phenethylamine, benzylamine — concentrated in CNS + platelets. Pharmacology: irreversible non-selective inhibitors (phenelzine, tranylcypromine, isocarboxazid) — antidepressants with the famous tyramine hypertensive-crisis risk (dietary tyramine bypasses MAO-A in the gut + reaches systemic circulation, releases stored norepinephrine). Selective + reversible MAO-A: moclobemide (less tyramine risk). Selective MAO-B: SELEGILINE (Parkinson disease adjunct + transdermal for depression; reversible loss-of-selectivity at high doses), RASAGILINE (newer; once-daily). Selegiline metabolizes to amphetamine + methamphetamine — explains some of its CNS effects.
Organ Systems
nervous
digestive
Pathway Steps
serotonin → 5-hydroxyindoleacetaldehyde — via MAO-A → ALDH → 5-HIAA (urinary marker). MAO-A preferentially deaminates serotonin (and norepinephrine) → 5-HIAA, the urinary carcinoid marker. MAO-A inhibition raises synaptic serotonin/NE (antidepressant MAOIs) and underlies the tyramine “cheese reaction”.
norepinephrine → dihydroxyphenylglycoaldehyde — via MAO-A → ALDH/AR → VMA / DHPG (urinary markers). MAO-A degrades norepinephrine toward DHPG/VMA (urinary catecholamine markers used in pheochromocytoma workup). MAO sits on the outer mitochondrial membrane, policing the cytosolic monoamine pool not protected inside vesicles.
dopamine → dopal — via MAO-A + MAO-B → ALDH → DOPAC → HVA (urinary marker). Dopamine is a substrate for both MAO-A and MAO-B → DOPAC → HVA. MAO-B predominates in the basal ganglia, so selective MAO-B inhibitors (selegiline, rasagiline) raise dopamine in Parkinson’s with less tyramine interaction; the DOPAL intermediate is itself neurotoxic.
Known Modulators
selegiline (inhibitor) — MAO-B (selective at low dose; non-selective at high)