Basic Neurosciences · Paper A
Monoamine metabolism (MAO)
This concept covers how the brain breaks down its monoamine messengers (serotonin, dopamine and noradrenaline), and the breakdown products and enzymes the exam likes to test. Tracing one dopamine molecule from release to breakdown shows the enzyme responsible and the exact chemical it becomes, both testable facts. A CSFCerebrospinal fluid, the fluid that cushions the brain and spinal cord.Read more → or urine sample with an abnormal breakdown-product level points a clinician back to a specific transmitter system, not a vague 'chemical imbalance.'
The key enzymes are MAOMonoamine oxidase, an enzyme that breaks down mood-related brain chemicals.Read more → (monoamine oxidase) and COMT (catechol-O-methyltransferase). MAO-A breaks down serotonin (to a product called 5-HIAA), noradrenaline and tyramine; MAO-B breaks down dopamine; both handle tyramine. e.g. a patient on selegiline, an MAO-B-selective drug used in Parkinson's disease: because it spares MAO-A, it carries much less of the tyramine dietary risk than an irreversible MAOIMonoamine oxidase inhibitor, an older antidepressant with strict food and drug interaction rules.Read more → (monoamine oxidase inhibitor) antidepressant. COMT adds a methyl group to the catecholamines in the synapseThe tiny gap between two nerve cells where a chemical signal passes from one to the other.Read more →. Dopamine's main breakdown product is HVA (homovanillic acid), and serotonin's is 5-HIAA. The enzyme-selectivity of a drug, not just its class name, predicts its dietary and interaction risk.
A vignette names a transmitter, its breakdown enzyme (MAOMonoamine oxidase, an enzyme that breaks down mood-related brain chemicals.Read more →-A, MAO-B or COMT) or its metabolite, and asks you to pair them, or reports a low CSFCerebrospinal fluid, the fluid that cushions the brain and spinal cord.Read more → metabolite level. Remember HVA marks dopamine breakdown and 5-HIAA marks serotonin breakdown, and a drug's enzyme selectivity predicts its dietary tyramine risk.
Every psychiatric drug that touches serotonin, dopamine or noradrenaline eventually runs into the enzymes that break these chemicals down. If you do not know which enzyme handles which transmitter, you cannot predict why one drug is dangerous with cheese and another is not, or why a Parkinson's disease drug and an antidepressant sit at opposite ends of the same enzyme family. This page builds that map from scratch, then uses it to explain real prescribing decisions.
Monoamines are a chemical family that includes the serotonin, dopamine and noradrenaline. Once released and used, they must be cleared away, and the body does this mainly with two enzymes. (monoamine oxidase) breaks monoamines down by removing an amine group, a reaction called oxidative deamination. COMT (catechol-O-methyltransferase) breaks down catecholamines (dopamine and noradrenaline, but not serotonin) by adding a methyl group, a reaction called methylation. MAO comes in two subtypes, MAO-A and MAO-B, and each prefers different substrates.
The biggest mistake is assuming all MAOIs (monoamine oxidase inhibitors) carry the same risk just because they share a class name. They do not. Whether a drug is selective for -A or MAO-B, and whether it binds reversibly or irreversibly, changes the danger completely: an irreversible, non-selective carries a real dietary hypertensive crisis risk, while a reversible MAO-A-selective drug like moclobemide, or an MAO-B-selective drug like selegiline, carries much less of that risk. Learn the selectivity, not just the class label.
Imagine tracing one dopamine molecule from the moment it is released into a (the tiny gap between two neurons) to the moment it disappears. It can be pumped back into the neuron that released it, or it can be caught by a degrading enzyme sitting nearby. If catches it, dopamine becomes an inactive breakdown product called HVA (homovanillic acid). If COMT catches it first, a different breakdown pathway runs, but the two enzymes often work in sequence rather than in isolation. Serotonin has no COMT pathway at all: it is broken down by MAO alone, into a product called 5-HIAA (5-hydroxyindoleacetic acid). Knowing which product belongs to which transmitter is exactly what exam stems test.
-A preferentially breaks down serotonin and noradrenaline, and also handles tyramine, a substance found in aged cheese, cured meat and some fermented foods. Because MAO-A is the enzyme antidepressants target, it is central to the classic (monoamine oxidase inhibitor) drug class.
-B preferentially breaks down dopamine. Selegiline, a drug used in Parkinson's disease, is MAO-B selective, meaning it spares MAO-A and therefore carries much less of the tyramine dietary risk than an irreversible, non-selective antidepressant.
COMT works on the catecholamines (dopamine and noradrenaline) in the itself, rather than inside the neuron, and does not touch serotonin at all. A well-known genetic variant, COMT val158met, changes how efficiently the enzyme works and slightly alters dopamine levels in the (the front part of the brain involved in planning and working memory).
It is easy to muddle inhibition with COMT inhibition, or to muddle an MAOI's risk profile with an SSRI's. COMT inhibitors, used in Parkinson's disease to extend the effect of levodopa, work on a completely different enzyme, do not touch serotonin at all, and do not carry the tyramine dietary risk that defines MAOIs: a question describing a "cheese reaction" is never testing a COMT inhibitor. An (selective serotonin reuptake inhibitor) is also frequently confused with an because both raise serotonin levels, but an SSRI works by blocking reuptake, not by blocking the breakdown enzyme, and combining an SSRI with an MAOI is specifically dangerous because it can cause serotonin toxicity (): which is why an adequate washout period is required when switching between the two classes, not just when switching within the MAOI class itself.
Monoamine breakdown products can act as research biomarkers, but rarely as a routine diagnostic test. A low level of 5-HIAA in the CSF (cerebrospinal fluid, the fluid bathing the brain and spinal cord) has been linked in research studies to impulsive aggression and suicidality, though it is never used as a standalone diagnostic investigation in routine clinical screening. In the rare, inherited Brunner syndrome, a completely absent -A gene causes marked impulsive aggression, which is one of the clearest human demonstrations that this enzyme system has real behavioural consequences, not just biochemical ones, and which is confirmed by genetic testing rather than by measuring a breakdown product.
Because traditional, irreversible MAOIs block both -A and MAO-B everywhere in the body, they cannot safely be combined with tyramine-rich food: unmetabolised tyramine builds up and can trigger a dangerous hypertensive crisis. The BNF (British National Formulary) and the Maudsley Prescribing Guidelines both carry strict dietary warnings and washout-period rules for anyone switching onto or off an . This is a genuine treatment and prescribing hazard, not a theoretical one, which is why MAOIs are rarely first-line and are usually reserved for treatment-resistant depression under specialist management. Moclobemide, a reversible MAO-A inhibitor, is displaced from the enzyme by dietary tyramine itself, so it carries a much smaller food-interaction risk than an irreversible MAOI, and this selectivity difference is a common exam discriminator.
Suppose a patient established on long-term selegiline for Parkinson's disease is switched, for depression, onto an irreversible non-selective without an adequate washout period. Because both drugs now inhibit broadly, this combination risks a serious drug interaction (serotonin toxicity or a hypertensive crisis), which is exactly the kind of prescribing scenario the Maudsley guidelines exist to prevent.
Candidates often muddle which enzyme is inhibited by which drug, or forget that COMT does not touch serotonin. Another frequent trap is assuming all MAOIs carry the same dietary risk: selectivity and reversibility both matter, not just the drug class name.
-A clears serotonin and noradrenaline, MAO-B clears dopamine, and COMT clears catecholamines only: enzyme selectivity and reversibility, not the drug class label, is what actually predicts an MAOI's dietary and interaction risk.