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Melatonin as a naturally occurring co‐substrate of quinone reductase‐2, the putative MT 3 melatonin membrane receptor: hypothesis and significance
Author(s) -
Tan DunXian,
Manchester Lucien C.,
Terron M. Pilar,
Flores Luis J.,
Tamura Hiroshi,
Reiter Russel J.
Publication year - 2007
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2007.00513.x
Subject(s) - melatonin , melatonin receptor , binding site , flavin adenine dinucleotide , receptor , biochemistry , biology , enzyme , flavin group , chemistry , biophysics , medicine , endocrinology , cofactor
The nature of the MT 3 melatonin receptor/binding site has been a long pondered mystery for scientists. Even though it is a presumptive membrane receptor, neither its transduction cascade nor its biological consequences, after its stimulation, have been uncovered. Moreover, solid data support the idea that the MT 3 melatonin binding site is an enzyme, quinone reductase 2 (QR 2 ), rather than a membrane melatonin receptor. Based on the data available and our preliminary studies, we hypothesize that melatonin is a co‐substrate of QR 2 . We surmise that melatonin binds to a co‐substrate binding site (MT 3 binding site) donating an electron to the enzyme co‐factor, flavin adenine dinucleotide (FAD). FAD can be reduced to either FADH or FADH 2 while melatonin is converted to N 1 ‐acetyl‐ N 2 ‐formyl‐5‐methoxykynuramine and/or cyclic 3‐hydroxymelatonin. QR 2 is considered to be a detoxifying and antioxidant enzyme and its behavior changes depending on available co‐substrates. As a naturally occurring substance, melatonin’s levels fluctuate with the light/dark cycle, with aging and with health/disease state. As a result, these alterations in melatonin production under physiological or pathological conditions would probably influence the activity of QR 2 .