Functions of MAO

What are these things you call enzymes?

For those of you that need a quick review or for those that want an easy crash course, enzymes act on other molecules, making small changes so that they will becomes more useful to the body. They are like repair stations where you take your car, because the car itself is not changed, but some part of it might be replaced by something else, or even taken off so that it will work better. After being worked on by several enzymes, one molecule can have many parts of it changed quite quickly. Now that we have that under our belts, we can look at what makes MAO enzymes special.

What do MAO enzymes do?

The two types of MAO enzymes we know of do two very important things in our bodies. The main thing they do is take off nitrogen-containing amine groups from the molecules they work on. The deamination of aromatic amines is crucial to our ability to digest our food and resume normal cellular activity following release of neurotransmitters. MAO-A helps us digest foods which contain amine groups, which are known as dietary amines (serotonin, tryptamine, tyramine, and 2-phenylethylamine), and both types of MAO inactivate catecholamine neurotransmitters such as dopamine, adrenaline, noradrenaline, and histamine.

My friend comes up to me and says that he has low MAO-B activity.
Could this mean anything interesting?

We are not saying that you the key to diagnosing your friend and every other student at a given university, but when it comes to psychiatric and movement problems, yes, MAO-B seems to show up as one of the guys that tell interesting stories. In general, low platelet MAO-B can be an indicator for vulnerability to psychiatric disorders. These disorders can range from sensation-seeking behavior (committing crimes or committing suicide) to alcoholism to being a cigarette smoker, though this last one is not necessarily a psychiatric problem.

On the other hand, if your friend has high MAO-B activity, he may be vulnerable to depression, panic disorder, or chronic schizophrenia. He also resembles people with Parkinsons disease, Alzheimers disease, and epilepsy. These disease can all be treated with MAO-inhibitors. Remember that the reason MAO can have such drastic effects is that it digests neurotransmitters which are used as some of the most basic forms of communication in the brain. When basic communication is impaired, major problems come up, as you can see.

If you did not have any MAO at all, you could be a victim of Norrie disease. Chances are good that you would know it, because this disease is pretty severe. Norrie disease is linked to the X-chromosomes, and is very rare. It causes congenital blindness, mental retardation, and autistic-like behavior. Thank your mom for giving you MAO enzymes.

What exactly happens when there's too much MAO?

If MAO is good for us in terms of digesting our food for us, and helping our brains clean up after the neurons spill neurotransmitters all over, what could be meant by having too much? What we find is that during the process of cleaning, some hydrogen peroxide is created, which is normally cleaned up and causes no problem. If there is a malfunction in how MAO works, you can get a build-up of hydrogen peroxide in the brain. This is where the problem lies.

During normal digestion of dopamine, for example, there are two steps to the process. MAO-B will deaminate dopamine to form an aldehyde, some ammmonia, and some hydrogen peroxide. The hydrogen peroxide usually degenerates into water in the presence of glutathione peroxidase. However, in the presence of Iron, the hydrogen peroxide is broken down into hydroxide ion radicals, which then go on to destroy things like cell membranes. The cell membranes which are in the area are usually dopaminergic neurons, so this means that there is immediate damage in the dopaminergic pathways. This will explain why Parkinsons patients suffer so much.

The idea has been that if it were possible to reduce how much hydrogen peroxide was produced, brain damage could be avoided. There are long lists available that can tell you which inhibitors the laboratories have created, and which ones are thought to work best, but at the same time, it has been found that the brain has its own way of inhibiting MAO. These are isoquinolines. Not much is known about what they do, but the fact that they exist indicates that the brain has its own mechanisms for dealing with too much MAO. The possibilties that these endogenous MAO inhibitors provide have yet to be explored.

What does the active site look like?

We know that the basic structures of both types of MOA are the same. You will notice in the figure below that the three rings in the center, and the structures they are attached to are identical. The parts that we are interested in, the parts that make MAO-A different from MAO-B, are the active sites. However, we do not yet know what makes them different, and so they are indicated in the lower left-hand corners of the molecules by different shapes and colors. The only way that we know that they are different is because when we put different MAO-substrates into a person's body, they are digested differently. So some of the substrates which are specific to MAO-A and MAO-B are listed right below them.

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