MAOA

Monoamine oxidase A (MAOA) is a mitochondrial enzyme that degrades monoamine neurotransmitters, including serotonin, norepinephrine, and dopamine, as well as trace amines such as tyramine. It is part of the monoamine oxidase family, with MAOA and MAOB encoded by distinct genes and differing in tissue distribution and substrate preference. MAOA preferentially metabolizes serotonin and norepinephrine and, to a lesser extent, dopamine, while MAOB more readily metabolizes phenylethylamine; both enzymes contribute to overall monoamine catabolism in the brain and peripheral tissues.

The MAOA gene is located on the X chromosome (Xp11.3). The enzyme is expressed in multiple tissues, notably in the brain, liver, and intestine. MAOA activity is regulated at transcriptional and post-transcriptional levels, and genetic variation in the MAOA promoter region affects expression. A common feature is the variable number of tandem repeats (VNTR) that can influence transcriptional strength, producing individuals with relatively high- or low-activity MAOA alleles.

Clinically, MAO inhibitors (MAOIs) inhibit MAO enzymes to increase synaptic levels of monoamines. They include nonselective, irreversible inhibitors (e.g., phenelzine, tranylcypromine) and reversible MAO-A–selective agents (e.g., moclobemide). Dietary restriction is often required with nonselective MAOIs to avoid hypertensive crises from tyramine-containing foods. MAOIs interact with many psychotropic drugs, raising the risk of serotonin syndrome.

Genetic MAOA deficiency causes Brunner syndrome, an X-linked condition characterized by impulsive aggression and mild cognitive impairment in some cases. MAOA is also a focus of research in psychiatry and neuroimaging, with radioligands used to measure MAO-A density in vivo.