Monoamine breakdown
Monoamine oxidase A (MAO-A)
Also searched as Monoamine oxidase A (MAO-A).
This is the enzyme that ends the signal. Serotonin and noradrenaline are its substrates, so the more of it that is working, the less of them survives to act. That makes MAO-A a target you want turned down when mood is the goal — which is exactly what the classical antidepressant MAOIs do. The catch is that MAO-A in the gut is also what disposes of dietary tyramine, and blocking it lets tyramine reach the circulation, displace noradrenaline and drive blood pressure sharply upward. That is the reason MAO-A inhibition carries a food interaction and MAO-B inhibition largely does not.
In depth
Monoamine oxidase A, sitting on the outer mitochondrial membrane, breaks down serotonin and noradrenaline. It is concentrated in the gut, liver and placenta as well as the brain, which is why inhibiting it has consequences far outside the head.
What drives it
Gut barrier reduces it.
Indigenous gut microbiota promote serotonin biosynthesis from colonic enterochromaffin cells; the mechanism is dual — specific species facilitate conversion of tryptophan to serotonin and separately suppress MAO-A activity via short-chain fatty acids, raising serotonin bioavailability by both synthesis and reduced degradation. This edge carries the degradation limb; the gut → serotonin link carries the synthesis limb, and both rest on the same source. gut-derived neurotransmitters must cross the blood-brain barrier, so a peripheral MAO-A effect is not automatically a central one. Yano 2015, Cell 161:264. PMID 25860609
What it drives
It reduces Mood (serotonin).
10.3389/fphar.2020.593416 — Serotonin and norepinephrine are substrates of MAO-A. MAO-A is distributed mainly in the placenta, gut and liver. Degradative enzyme, so the edge is inhibitory: more MAO-A activity, less serotonin. StatPearls NBK539848 — Monoamine Oxidase Inhibitors. doi 10.3389/fphar.2020.593416
It reduces Alertness chemical.
Noradrenaline is a substrate of MAO-A; MAO-A is highly expressed in noradrenergic neurons such as the locus coeruleus. Degradative, therefore inhibitory. StatPearls NBK539848 — Monoamine Oxidase Inhibitors ; Sci Rep 2022, PMC8742005 — Phenethylamine is a substrate of monoamine oxidase B in the paraventricular thalamic nucleus. PMC8742005
It reduces Motivation.
10.1016/j.nbd.2021.105587 — Dopamine and tyramine are metabolized by both MAO-A and MAO-B — this edge is drawn alongside the monoamine oxidase B → dopamine link because neither isoform accounts for dopamine alone. StatPearls NBK539848 — Monoamine Oxidase Inhibitors. doi 10.1016/j.nbd.2021.105587
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.