MAO-B

Monoamine Oxidase A (MAO-A)

Monoamine Oxidase A (MAO-A) is an enzyme that plays a critical role in the metabolism of monoamines, which are neurotransmitters that include serotonin, norepinephrine, and dopamine. This enzyme is located in the outer membrane of mitochondria in cells throughout the body, including the brain, liver, and gastrointestinal tract.

Function

MAO-A is responsible for the oxidative deamination of monoamines, a process that involves the removal of an amine group from a molecule. This reaction results in the breakdown of neurotransmitters, thereby regulating their levels in the synaptic cleft and influencing mood, arousal, and emotional responses.

The enzyme catalyzes the following general reaction:

RCH₂NH₂ + O₂ + H₂O → RCHO + NH₃ + H₂O₂

In this reaction, the amine (RCH₂NH₂) is converted into an aldehyde (RCHO), with the release of ammonia (NH₃) and hydrogen peroxide (H₂O₂).

Genetic and Molecular Structure

The MAO-A gene is located on the X chromosome at Xp11.3. It encodes a protein that is approximately 527 amino acids in length. The structure of MAO-A includes a flavin adenine dinucleotide (FAD) cofactor, which is essential for its enzymatic activity.

Clinical Significance

MAO-A has been implicated in various psychiatric and neurological disorders. Abnormal activity of this enzyme can lead to altered levels of neurotransmitters, contributing to conditions such as depression, anxiety, and aggression. Inhibitors of MAO-A, known as MAO inhibitors (MAOIs), are used as antidepressants and in the treatment of other mood disorders.

MAO-A Deficiency

A deficiency in MAO-A activity, often due to genetic mutations, can result in a condition known as Brunner syndrome. This rare disorder is characterized by impulsive behavior, mild intellectual disability, and mood swings.

Inhibitors

MAO-A inhibitors are a class of drugs that prevent the breakdown of monoamines, thereby increasing their availability in the brain. These inhibitors can be selective or non-selective, with selective MAO-A inhibitors specifically targeting the MAO-A isoform.

Examples of MAO-A inhibitors include:

• Moclobemide
• Clorgyline

Research and Future Directions

Ongoing research is exploring the role of MAO-A in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Understanding the enzyme's function and regulation may lead to new therapeutic strategies for these and other conditions.

Also see

• Monoamine Oxidase B
• Neurotransmitter
• Depression (mood disorder)
• Antidepressant