Monoamine oxidase (MAO) is an enzyme that breaks down key brain chemicals, including serotonin, dopamine, and norepinephrine. By clearing these neurotransmitters after they’ve done their job, MAO acts as a built-in regulator, preventing them from building up to excessive levels. It also processes certain compounds from food and plays a protective role in the gut.
How MAO Breaks Down Neurotransmitters
MAO performs a chemical reaction called oxidative deamination. In practical terms, it strips a nitrogen-containing piece off a neurotransmitter molecule, converting it into an aldehyde, a simpler compound. That aldehyde is then quickly converted by other enzymes into either an acid or an alcohol that the body can safely dispose of. The reaction also produces hydrogen peroxide and ammonia as byproducts, both of which are potentially toxic and must be neutralized by other cellular defense systems.
Each neurotransmitter follows a slightly different breakdown path. Serotonin gets converted into a compound called 5-HIAA, which is eventually excreted. Dopamine is converted into DOPAC and then into homovanillic acid (HVA). Norepinephrine has multiple possible breakdown routes, but they all start with MAO snipping off that same nitrogen group. In every case, the end result is the same: the signaling molecule is deactivated so the neuron can reset and fire again cleanly.
MAO-A and MAO-B: Two Versions, Different Jobs
The body makes two forms of the enzyme. MAO-A preferentially breaks down serotonin, norepinephrine, epinephrine, and melatonin. MAO-B targets a different set of molecules, primarily phenylethylamine (a trace amine involved in attention and mood) and benzylamine.
Dopamine has traditionally been considered a shared substrate, processed by both forms. But more recent research using real-time measurements of dopamine in living brain tissue tells a clearer story. When researchers blocked MAO-A in the striatum (a brain region central to movement and reward), dopamine levels rose by about 47% over two hours. Blocking MAO-B had no effect at all. The same pattern held for the speed at which dopamine was cleared after being released: MAO-A inhibition slowed clearance significantly, while MAO-B inhibition did nothing. So in the brain, MAO-A appears to be the dominant enzyme for dopamine regulation as well.
MAO-B, meanwhile, has a newly recognized role in producing GABA, the brain’s main inhibitory neurotransmitter. This means the two forms of the enzyme have more distinct jobs than scientists previously appreciated: MAO-A handles neurotransmitter cleanup, while MAO-B contributes to a different kind of signaling entirely.
Where MAO Lives in the Body
MAO is anchored to the outer membrane of mitochondria, the energy-producing structures inside cells. This location puts it right at the boundary where molecules pass in and out of the cell’s power supply, giving it access to neurotransmitters that have been taken back up into the nerve terminal after signaling.
The enzyme is found throughout the body, not just in the brain. The liver, intestinal lining, and kidneys all contain substantial amounts. MAO in the gut wall serves as a first-pass filter, breaking down potentially dangerous amines in food before they can enter the bloodstream. This is particularly important for tyramine, an amine found in aged cheeses, cured meats, fermented foods, and red wine. Without MAO in the intestinal lining deactivating tyramine, large amounts would reach the circulation and cause dangerous spikes in blood pressure.
What Happens When MAO Is Too Active
Higher-than-normal MAO activity means neurotransmitters get broken down faster than usual, which can lower serotonin, dopamine, and norepinephrine levels. Brain imaging studies using PET scans have found that people experiencing major depressive episodes have elevated MAO-A density in the prefrontal cortex and anterior cingulate cortex, two regions involved in mood regulation and decision-making. The more severe the depression and the more pronounced certain symptoms (like increased appetite and excessive sleeping, sometimes called “reversed” neurovegetative symptoms), the higher the MAO-A levels tended to be.
This connection helps explain why a class of antidepressants called MAO inhibitors can be especially effective for people with these specific symptom patterns. By blocking the enzyme, these medications allow serotonin, dopamine, and norepinephrine to linger longer in the synapse, strengthening their signals.
MAO Inhibitors and the Tyramine Problem
MAO inhibitors were among the first antidepressants ever developed, but they come with a well-known dietary restriction. Older, nonselective MAO inhibitors block both MAO-A and MAO-B permanently (the enzyme must be rebuilt from scratch, which takes about two weeks). This means tyramine from food can no longer be neutralized in the gut or liver. The result is the “cheese effect,” where eating tyramine-rich foods can trigger a hypertensive crisis, a sudden and dangerous rise in blood pressure.
Newer, reversible MAO-A inhibitors largely sidestep this problem. Because they bind loosely to the enzyme, a surge of tyramine from a meal can temporarily push them off, allowing enough MAO-A activity to handle the dietary load while still providing antidepressant effects in the brain.
The MAOA Gene and Behavior
The gene that codes for MAO-A comes in variants that produce different amounts of the enzyme. People with the lower-expression version make less MAO-A, meaning neurotransmitters get cleared more slowly. Research has linked this variant to higher impulsivity in males, though notably not in females. The same variant has also been associated with a history of abuse before age 15 in male subjects, suggesting the gene may interact with early life experiences to shape behavioral traits.
These findings do not mean the gene “causes” aggression or violence, despite sensationalized media coverage that once dubbed it the “warrior gene.” No direct link to mood disorders or suicide attempts has been found for this variant. The relationship appears to be more nuanced: the lower-activity version may increase vulnerability to the lasting psychological effects of childhood adversity, particularly in males.
MAO’s Role Beyond the Brain
MAO also functions as what pharmacologists call a phase I metabolic enzyme, meaning it helps the body process foreign chemicals. Beyond tyramine, it contributes to the metabolism of certain drugs and environmental compounds that contain amine groups. This role has historically been overlooked, but it has practical implications. If you’re taking a medication that MAO normally helps break down, adding an MAO inhibitor to the mix can cause that drug to accumulate to higher-than-expected levels. This is one reason MAO inhibitors carry a long list of drug interactions, not just dietary ones.
The enzyme’s byproducts also matter outside the brain. The hydrogen peroxide generated every time MAO breaks down a molecule is a reactive oxygen species, a type of molecule that can damage cells if it accumulates. In aging, MAO-B activity in the brain tends to increase, which means more hydrogen peroxide production. This has led researchers to investigate whether the oxidative stress from MAO activity contributes to the neuron loss seen in neurodegenerative conditions.