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Acetylserotonin O-methyltransferase (ASMT) is the terminal enzyme in the biosynthetic pathway of melatonin, responsible for converting N-acetylserotonin into the neurohormone melatonin [1, 2, 6]. Predominantly expressed in the pineal gland and the retina, ASMT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to the 5-hydroxyl group of N-acetylserotonin [4, 10]. Because melatonin is the master regulator of the circadian rhythm, the catalytic activity of ASMT is vital for maintaining synchronized sleep-wake cycles and seasonal biological timing [8, 14]. Clinical research has linked genetic variations, deletions, and reduced activity of ASMT to several neurodevelopmental conditions, most notably autism spectrum disorder (ASD), as well as psychiatric conditions such as depression, bipolar disorder, and chronic insomnia [5, 7, 12]. Consequently, ASMT serves as a critical focus for investigating the molecular basis of circadian-related pathologies and remains a target of interest for therapies designed to modulate endogenous melatonin production [13].
Acetylserotonin O-methyltransferase (ASMT) catalyzes the final step of melatonin synthesis by transferring a methyl group from the cofactor S-adenosyl-L-methionine (SAM) to the 5-hydroxyl group of N-acetylserotonin, resulting in the production of melatonin and S-adenosyl-L-homocysteine (SAH).
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