hydroxyindoleOmethyltransferase

Hydroxyindole O-methyltransferase (HIOMT), also called acetylserotonin O-methyltransferase (ASMT), is a methyltransferase enzyme that catalyzes the final step of melatonin biosynthesis: the methylation of N-acetylserotonin to melatonin, using S-adenosyl-L-methionine as the methyl donor and producing S-adenosyl-L-homocysteine as a byproduct.

HIOMT is expressed in the pineal gland and in various extra-pineal tissues such as the retina, gut, and brain. In mammals, the rate-limiting step of melatonin production is typically performed by arylalkylamine N-acetyltransferase (AANAT), which supplies N-acetylserotonin; HIOMT acts on NAS to generate melatonin. The enzyme’s activity is linked to circadian regulation and nocturnal melatonin secretion. Light exposure suppresses AANAT, reducing NAS availability, while HIOMT remains capable of completing the final methylation when NAS accumulates.

Genetically, the enzyme is encoded in humans by the ASMT gene and is commonly referred to by the HIOMT name. Variants in ASMT have been explored for potential associations with sleep and neurodevelopmental disorders, including autism, but findings to date are inconclusive.

Biochemical properties: the reaction requires SAM as a methyl donor and yields melatonin and SAH. HIOMT activity can be measured in pineal tissue or cultured cells, and its function is a component of the broader melatonin biosynthetic pathway that helps regulate circadian rhythms across species.