Melatonin is metabolized to N-acetyl serotonin and 6-hydroxymelatonin in man.
To investigate whether melatonin (aMT) can be metabolized to N-acetyl serotonin (NAS), a low dose of deuterated aMT was administered to four normal subjects, and their urine samples were analyzed for the presence of deuterated NAS and deuterated 6-hydroxymelatonin (6-HaMT). In one set of experiments, the urine samples were subjected to column chromatography to separate the glucuronide and sulfate conjugates for independent analysis. In another, an internal standard (NAS-sulfate) was used for quantification and total conjugate analysis. Measurement was by gas chromatography-mass spectrometry, and the molecular ions of deuterated and nondeuterated NAS and 6-HaMT were monitored. Deuterated aMT was metabolized to deuterated NAS and deuterated 6-HaMT. The proportion of NAS was less in the sulfate than in the glucuronide conjugates and, overall, represented 15% of the total. Since demethylation is not a pathway that occurs with other pineal methoxyindoles, even at a much larger dose, it seems to be a significant finding with regard to aMT. Thus, it may be important to elucidate the differential metabolism of aMT at different time points and in different age groups.
D000328:Adult; D001711:Biotransformation; D003903:Deuterium; D008401:Gas Chromatography-Mass Spectrometry; D005965:Glucuronates / Q000652:urine; D006801:Humans; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000652:urine; D012701:Serotonin / Q000031:analogs & derivatives* / Q000652:urine; D013431:Sulfates / Q000652:urine
D005965:Glucuronates; D013431:Sulfates; D012701:Serotonin; D003903:Deuterium; D008550:Melatonin; C006389:N-acetylserotonin; C012365:6-hydroxymelatonin