On the significance of an alternate pathway of melatonin synthesis via 5-methoxytryptamine: comparisons across species.
Melatonin is a phylogenetically ancient molecule. It is ubiquitously present in almost all organisms from primitive photosynthetic bacteria to humans. Its original primary function is presumable to be that of an antioxidant with other functions of this molecule having been acquired during evolution. The synthetic pathway of melatonin in vertebrates has been extensively studied. It is common knowledge that serotonin is acetylated to form N-acetylserotonin by arylalkylamine N-acetyltransferase (AANAT) or arylamine N-acetyltransferase (SNAT or NAT) and N-acetylserotonin is, subsequently, methylated to melatonin by N-acetylserotonin O-methyltransferase (ASMT; also known as hydroxyindole-O-methyltransferase, HIOMT). This is referred to as a classic melatonin synthetic pathway. Based on new evidence, we feel that this classic melatonin pathway is not generally the prevailing route of melatonin production. An alternate pathway is known to exist, in which serotonin is first O-methylated to 5-methoxytryptamine (5-MT) and, thereafter, 5-MT is N-acetylated to melatonin. Here, we hypothesize that the alternate melatonin synthetic pathway may be more important in certain organisms and under certain conditions. Evidence strongly supports that this alternate pathway prevails in some plants, bacteria, and, perhaps, yeast and may also occur in animals.
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Dun-Xian
DX
Tan
Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Göttingen, Germany.
Rüdiger
R
Hardeland
Department of Biotechnology, Bioenergy Research Center, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, South Korea.
Kyoungwhan
K
Back
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Lucien C
LC
Manchester
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Moises A
MA
Alatorre-Jimenez
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Russel J
RJ
Reiter
D008735:5-Methoxytryptamine / Q000378:metabolism*; D000107:Acetylation; D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D006801:Humans; D008550:Melatonin / Q000096:biosynthesis*; D008745:Methylation; D010944:Plants / Q000378:metabolism*; D013045:Species Specificity; D015003:Yeasts / Q000378:metabolism*
D008735:5-Methoxytryptamine; D008550:Melatonin
5-methoxytryptamine; N-acetylserotonin O-methyltransferase; antioxidant; arylalkylamine N-acetyltransferase; hydroxyindole-O-methyltransferase; melatonin; serotonin; serotonin N-acetyltransferase