Monoamine oxidase

monoamine oxidase A
Ribbon diagram of a monomer of human MAO-A, with FAD and clorgiline bound, oriented as if attached to the of a . From PDB: 2BXS​.
Identifiers
Symbol	MAOA
Entrez	4128
HUGO	6833
OMIM	309850
RefSeq	NM_000240
UniProt	P21397
Other data
Locus	Chr. X p11.4-p11.3

monoamine oxidase B
Ribbon diagram of human MAO-B. From PDB: 1GOS​.
Identifiers
Symbol	MAOB
Entrez	4129
HUGO	6834
OMIM	309860
RefSeq	NM_000898
UniProt	P27338
Other data
Locus	Chr. X p11.4-p11.3

L-Monoamine oxidases (MAO) (EC 1.4.3.4) are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase. They belong to the protein family of flavin-containing amine oxidoreductases.

In humans there are two types of MAO: MAO-A and MAO-B.

MAO-A appears at roughly 80% of adulthood levels at birth, increasing very slightly after the first 4 years of life, while MAO-B is almost non-detectable in the infant brain. Regional distribution of the monoamine oxidases is characterized by extremely high levels of both MAOs in the hypothalamus and hippocampal uncus, as well as a large amount of MAO-B with very little MAO-A in the striatum and globus pallidus. The cortex has relatively high levels of only MAO-A, with the exception of areas of the cingulate cortex, which contains a balance of both. Autopsied brains demonstrated the predicted increased concentration of MAO-A in regions dense in serotonergic neurotransmission, however MAO-B only correlated with norepinephrine.

Monoamine oxidases catalyze the oxidative deamination of monoamines. Oxygen is used to remove an amine group from a molecule, resulting in the corresponding aldehyde and ammonia. Monoamine oxidases contain the covalently bound cofactor FAD and are, thus, classified as flavoproteins. Monoamine oxidase A and B share roughly 70% of their structure and both have substrate binding sites that are predominantly hydrophobic. Two tyrosine residues (398, 435, 407 and 444) in the binding pocket that are commonly involved in inhibitor activity have been hypothesized to be relevant to orienting substrates, and mutations of these residues are relevant to mental health. Four main models have been proposed for the mechanism of electron transfer (single electron transfer, hydrogen atom transfer, nucleophilic model, and hydride transfer) although there is insufficient evidence to support any of them.