Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P30044 (
antioxidant enzyme
)
8,037
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The nature of the MT3 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 MT3 melatonin binding site is an enzyme,
quinone reductase 2
(
QR2
), rather than a membrane melatonin receptor. Based on the data available and our preliminary studies, we hypothesize that melatonin is a co-substrate of
QR2
. We surmise that melatonin binds to a co-substrate binding site (MT3 binding site) donating an electron to the enzyme co-factor, flavin adenine dinucleotide (FAD). FAD can be reduced to either FADH or FADH2 while melatonin is converted to N1-acetyl-N2-formyl-5-methoxykynuramine and/or cyclic 3-hydroxymelatonin.
QR2
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
QR2
.
...
PMID:Melatonin as a naturally occurring co-substrate of quinone reductase-2, the putative MT3 melatonin membrane receptor: hypothesis and significance. 1791 May 98
Melatonin and its immediate precursor, N-acetylserotonin (NAS), exert antidepressant effects in experimental models and clinical studies. We reported that melatonin and NAS decreased immobility time (an indicator of antidepressant activity) in the mouse tail suspension test. Melatonin type 3 receptor (MT3) was identified as the same protein as
quinone reductase 2
(
QR2
) detoxifying and
antioxidant enzyme
. To further elucidate the role of
QR2
/MT3 in antidepressant action of NAS and melatonin, we studied the effect of
QR2
/MT3 agonist and antagonist in a tail suspension test.
QR2
/MT3 agonist 5-MCA-NAT decreased, while the
QR2
/MT3 antagonist prazosin increased the duration of immobility in the tail suspension test in a dose-dependent manner. Prazosin, in a dose that did not affect the duration of immobility, attenuated the antidepressant-like effect of NAS, melatonin, and typical tricyclic antidepressant, amitriptyline, in the tail suspension test. Our results suggest that the modulation of
QR2
/MT3 might contribute to mechanism(s) of antidepressant effect. New antidepressants might be searched among the agonists of
QR2
/MT3.
...
PMID:Quinone reductase 2 and antidepressant effect of melatonin derivatives. 2063 17
