Dopamine quinone is substrate of the NRH: Quinone Reductase enzyme (QR2) in the retina. The capability of accumulates endogenous dopamine in a neural tissue explains the association of certain neuropsychiatric diseases with polymorphisms in the QR2 promoter that causes overexpression via loss of the capability to bind repressors. However, QR2 doubly reduce other small compounds present in neural and non-neural tissues, being its physiology tissue dependent. In this context, the function of the neurohormone melatonin and analogues in the active site of this multifunctional enzyme is discussed in this mini review. The flavoenzyme Ribosyldihydronicotinamide dehydrogenase (quinone), EC 1.10.99.2 (NRH: Quinone Reductase, QR2) is an unpredicted member of the quinone reductase family of phase II detoxifying enzymes [1] because its detoxifying activity produces reactive quinones and free radicals [2] . In addition, the natural QR2 cosubstrates are NRH (N-ribosyl-dihydronicotinamide) and NMH (N-methyl-dihydronicotinamide) [3][4][5] . This enzyme is inhibited by quercetin, resveratrol, benzo[a]pyrene [3][4][5] , some protein kinases inhibitors [6,7] , antimalarial drugs [8] and many others synthetized analogues compounds [9,10] . QR2 is able to doubly reduce quinones such as menadione, a synthetic vitamin K precursor, the coenzymes Q0-10
Keywords[11] and anti-cancer pro-drugs such as CB1954 [12] . The kinetics of this 24-kDa cytosolic flavoprotein proceeds via a double displacement mechanism [13] . Through this mechanism, FAD is reduced by the cosubstrate, which then diffuses out from the binding pocket, permitting occupation of the active site by the substrate. In this type of catalysis, the excess substrate competes with the cosubstrate, or vice-versa, resulting in the inhibition of the enzyme. Therefore, the effect of small compounds in QR2 catalysis is concentration dependent. The capability to accept a myriad of quinones and small compounds as substrates turn QR2 into a multifunctional enzyme. In mammals, QR2 is present in different tissues [1,14] that contain different endogenous compounds. Additionally, each tissue is susceptible to be targeted by exogenous compounds with the ability to function as substrates for QR2 catalysis. Therefore, QR2 physiology appears to be tissue-dependent. Dopamine plays a role in light-adapting events in retinal physiology [15] , whereas in the brain, attention, memory and other cognitive processes are regulated by dopamine [16] . A great achievement in the investigation of QR2 physiology was the finding that ortho-quinones such as dopa-quinone RESEARCH HIGHLIGHT