Trait: Dopamine Metabolism (MAO)
Dr Haran Sivapalan
January 13, 2020
Your previous trait looked at how effectively you break down dopamine based on the activity of one enzyme in particular: COMT (catechol-O-methyltransferase).
COMT is just one of the enzymes that breaks down (or metabolizes) dopamine. Another key enzyme is MAO (Monoamine oxidase).
This trait looks at the activity of your MAO enzyme, which in turn influences your levels of dopamine.
A reminder about dopamine
We’ve described the functions of dopamine in detail in your Dopamine Metabolism trait. To recap briefly, dopamine is an important hormone and neurotransmitter (nerve signalling chemical). As a neurotransmitter, dopamine transmits signals between nerves (or neurons) in the brain and central nervous system.
Brain circuits that use dopamine are involved in the control of movement, reward, motivation, emotion and our behavioural response to stress.
The rate of breakdown of dopamine by enzymes such as COMT and MAO affects levels of dopamine within these brain circuits. This, accordingly, alters nerve / neuronal activity in the same brain circuits, which influences our cognitive function and behavior: i.e. the way we think, feel and respond.
What is MAO?
Rather than referring to the author of “The Little Red Book”, MAO stands for Monoamine Oxidase.
It’s an enzyme that breaks down our monoamine neurotransmitters, a group of related nerve-signalling molecules which includes adrenaline, noradrenaline, serotonin, histamine and dopamine.
We have two types of MAO enzyme:
These two types of MAO enzyme are very similar in structure, but differ in two main respects:
1. Distribution in the brain – MAO-A is principally found within neurons (nerve cells), in cortex – the outermost layer of our brain that carries out “higher-order” functions such as planning, attention and language.
By contrast, MAO-B tends to be produced by cells known as glial cells. Unlike neurons, glial cells do not directly transmit nerve signals, but provide support to neurons. MAO-B is particularly abundant in the basal ganglia, the collection of structures in the brain that help to fine-tune movement.
2. Neurotransmitter breakdown – Although both MAO-A and MAO-B break down all monoamines, MAO-A preferentially acts on serotonin, noradrenaline and adrenaline.
By contrast, MAO-B preferentially breaks down dopamine.
Unless otherwise stated, when we refer to MAO, we are typically referring to both MAO-A and MAO-B.
- MAO stands for Monoamine Oxidase
- MAO is a key enzyme involved in the breakdown of dopamine.
- There are two main forms of MAO, which differ in their distribution in the brain and the neurotransmitters they act upon.
Why do we have MAO?
The MAO enzyme is particularly important for terminating nerve signals and therefore regulating activity in brain circuits.
When an electrical impulse reaches the end of a nerve (termed a pre-synaptic nerve), it triggers the release of neurotransmitters (in this case, dopamine) from specialized compartments called synaptic vesicles. The neurotransmitters then travel across a gap (called a synapse or synaptic cleft) and bind to receptors (in this case, dopamine receptors) on a receiving or ‘post-synaptic’ nerve.
The process of dopamine binding its receptor stimulates the receiving nerve, resulting in the nerve signal being conducted onwards. Shortly after, the dopamine detaches from its receptor and returns to the synaptic cleft. MAO within the synaptic cleft then breaks down dopamine.
If we did not produce MAO, the dopamine would linger within the synaptic cleft and quickly re-bind to dopamine receptors on the post-synaptic nerve. This would result in continued transmission of nerve signals and cause inappropriate activity within wider brain networks.
By degrading dopamine within the synaptic cleft, MAO helps to terminate nerve signals and, more broadly, regulate activity in brain networks.
How is dopamine degraded by MAO?
There are two main pathways by which dopamine is degraded.
Both of these pathways involve MAO, in addition to two other enzymes: COMT (catechol-O-methyltransferase) and ALDH [sometimes denoted AD] (aldehyde dehydrogenase).
The end product of both pathways is a molecule called HVA (homovanillic acid). HVA is then filtered out of the blood and excreted in our urine.
Dopamine --> DHPA --> DOPAC --> HVA
In one pathway, MAO first breaks down dopamine into an intermediate molecule called DHPA.
DHPA is subsequently degraded by the ALDH / AD enzyme into a molecule called DOPAC (3,4-Dihydroxyphenylacetic acid). DOPAC is then finally converted by the COMT enzyme into HVA.
Dopamine --> 3-MT --> MHPA --> HVA
In a second pathway, dopamine is first broken down by COMT into a molecule called 3-MT (3-methoxytyramine).
MAO then metabolizes 3-MT into another intermediate molecule called MHPA (3-methoxy-4-hydroxyphenylacetaldehyde).
In the final stage, MHPA is converted by the ALDH enzyme into HVA.
Why is the activity of MAO important?
As MAO breaks down dopamine within nerve synapses, our levels of dopamine are affected by the activity of our MAO enzyme.
In turn, our synaptic levels of dopamine influence the nerve activity of key brain circuits that underlie reward, motivation, personality, control of movement and response to stress.
Overall, then, MAO activity has a downstream effect on the way we think, feel, move and behave.
High MAO activity causes greater breakdown of dopamine. This will, all other things being equal, lead to lower levels of synaptic dopamine and lower activity within dopaminergic brain circuits.
Low MAO activity leads to reduced breakdown of dopamine. Assuming other factors (e.g. activity of other enzymes and receptors) remain unchanged, this will lead to higher levels of synaptic dopamine and higher activity within dopaminergic brain circuits.
- The activity of MAO affects nerve activity in key brain circuits that use dopamine.
- Your MAO activity can therefore influence the way you think, feel, move and behave.
At FitnessGenes we analyze single letter changes in your DNA called SNPs (Single Nucleotide Polymorphisms).
When a SNP occurs within a gene (which is a unit of DNA that codes for a protein), the change in DNA code can alter the structure, function, quantity and activity of the protein that is produced by that gene.
This is exactly what happens with your MAO-A gene, which encodes your MAO-A enzyme.
A SNP (rs6323) in your MAO-A gene gives rises to two gene variants.
One variant, called the ‘G’ allele, is associated with higher activity of the MAO-A enzyme. People who have one or two copies of the G allele have greater breakdown of dopamine. This would ordinarily lead to lower levels of dopamine in synapses and reduced activity in dopaminergic brain networks.
The other variant, called the ‘T’ allele, is linked to lower activity of the Consequently, the ‘A’ allele causes reduced breakdown of dopamine and higher levels of dopamine in brain networks.
Depending on what variant of the MAO-A gene you carry, you will respond differently to different exercise, dietary and supplement regimes. Check out your Insights and Actions for information that's personalized to you!