Arylalkylamine N-acetyltransferase (AANAT)

Arylalkylamine N-acetyltransferase (AANAT) is an acetyl-CoA-dependent enzyme that catalyzes the transformation of serotonin to N-acetylserotonin, the penultimate step in the biosynthesis of melatonin[1][2][5][6]. This reaction is considered a key regulatory point in melatonin production and thus in circadian rhythm regulation, particularly in vertebrates where AANAT is expressed mainly in the pineal gland and retina[1][2][4][6]. AANAT is part of the GCN5-related N-acetyltransferase (GNAT) superfamily, sharing conserved structural motifs and using acetyl-CoA as a cofactor for its acetylation reactions[1][2][3]. In mammals, its activity is tightly controlled in a rhythmic, light-dependent manner, providing a biochemical "time signal" through nightly melatonin synthesis[1][2]. Alternative roles exist in non-vertebrates, where aaNAT enzymes also contribute to detoxification, pigmentation, and other physiological processes[2][3]. Dysregulation of AANAT activity and melatonin synthesis is involved in disorders of circadian rhythm, sleep, and possibly mood and neurodegenerative conditions. There are no direct, clinically approved drugs that target AANAT, but modulation of melatonin signaling remains therapeutically important for sleep and circadian disorders[2][5].

Other names

serotonin N-acetyltransferaseSNATNATaaNAT

Enzyme inhibition (hypothetical or preclinical), Modulation via upstream or downstream regulation (therapeutic action mainly through influencing melatonin production)