Interactions of the antioxidant enzymes NAD(P)H: Quinone oxidoreductase 1 (NQO1) and NRH: Quinone oxidoreductase 2 (NQO2) with pharmacological agents, endogenous biochemicals and environmental contaminants.

Abstract

NAD(P)H:

Quinone Oxidoreductase 1 (NQO1) is an antioxidant enzyme that catalyzes the two-electron reduction of several different classes of quinone-like compounds (quinones, quinone imines, nitroaromatics, and azo dyes). One-electron reduction of quinone or quinone-like metabolites is considered to generate semiquinones to initiate redox cycling that is responsible for the generation of reactive oxygen species and oxidative stress and may contribute to the initiation of adverse drug reactions and adverse health effects. On the other hand, the two-electron reduction of quinoid compounds appears important for drug activation (bioreductive activation) via chemical rearrangement or autoxidation. Two-electron reduction decreases quinone levels and opportunities for the generation of reactive species that can deplete intracellular thiol pools. Also, studies have shown that induction or depletion (knockout) of NQO1 were associated with decreased or increased susceptibilities to oxidative stress, respectively. Moreover, another member of the quinone reductase family, NRH: Quinone Oxidoreductase 2 (NQO2), has a significant functional and structural similarity with NQO1. The activity of both antioxidant enzymes, NQO1 and NQO2, becomes critically important when other detoxification pathways are exhausted. Therefore, this article summarizes the interactions of NQO1 and NQO2 with different pharmacological agents, endogenous biochemicals, and environmental contaminants that would be useful in the development of therapeutic approaches to reduce the adverse drug reactions as well as protection against quinone-induced oxidative damage. Also, future directions and areas of further study for NQO1 and NQO2 are discussed.

• Authors: Md Harunur Rashid, Dinesh Babu, Arno G Siraki
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 345 Pg. 109574 (Aug 25 2021) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 34228969 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Environmental Pollutants
• Pharmaceutical Preparations
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human
• NRH - quinone oxidoreductase2
• Quinone Reductases

Topics

• Antioxidants (metabolism)
• Electron Transport
• Environmental Pollutants (metabolism)
• Humans
• NAD(P)H Dehydrogenase (Quinone) (metabolism)
• Pharmaceutical Preparations (metabolism)
• Protein Binding
• Quinone Reductases (metabolism)