Structure, Function, and Mechanism of Cytosolic Quinone Reductases

Mario A. Bianchet, Sabri Bora Erdemli, L. Mario Amzel

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Quinone reductases type 1 (QR1) are FAD-containing enzymes that catalyze the reduction of many quinones, including menadione (Vit K3), to hydroquinones using reducing equivalents provided by NAD(P)H. The reaction proceeds with a ping-pong mechanism in which the NAD(P)H and the substrate occupy alternatively overlapping regions of the same binding site and participate in a double hydride transfer: one from NAD(P)H to the FAD of the enzyme, and one from the FADH2 of the enzyme to the quinone substrate. The main function of QR1 is probably the detoxification of dietary quinones but it may also contribute to the reduction of vitamin K for its involvement in blood coagulation. In addition, the same reaction that QR1 uses in the detoxification of quinones, activates some compounds making them cytotoxic. Since QR1 is elevated in many tumors, this property has encouraged the development of chemotherapeutic compounds that become cytotoxic after reduction by QR1. The structures of QR1 alone, and in complexes with substrates, inhibitors, and chemotherapeutic prodrugs, combined with biochemical and mechanistic studies have provided invaluable insight into the mechanism of the enzyme as well as suggestions for the improvements of the chemotherapeutic prodrugs. Similar information is beginning to accumulate about another related enzyme, QR2.

Original languageEnglish (US)
Title of host publicationVitamin K
EditorsGerald Litwack
Pages63-84
Number of pages22
DOIs
StatePublished - Mar 27 2008

Publication series

NameVitamins and Hormones
Volume78
ISSN (Print)0083-6729

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ASJC Scopus subject areas

  • Physiology
  • Endocrinology

Cite this

Bianchet, M. A., Erdemli, S. B., & Amzel, L. M. (2008). Structure, Function, and Mechanism of Cytosolic Quinone Reductases. In G. Litwack (Ed.), Vitamin K (pp. 63-84). (Vitamins and Hormones; Vol. 78). https://doi.org/10.1016/S0083-6729(07)00004-0