Related Experiment Videos
Structures of mammalian cytosolic quinone reductases
C E Foster1, M A Bianchet, P Talalay
1Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Abstract:
The metabolism of quinone compounds presents one source of oxidative stress in mammals, as many pathways proceed by mechanisms that generate reactive oxygen species as by-products. One defense against quinone toxicity is the enzyme NAD(P)H:quinone oxidoreductase type 1 (QR1), which metabolizes quinones by a two-electron reduction mechanism, thus averting production of radicals. QR1 is expressed in the cytoplasm of many tissues, and is highly inducible. A closely related homologue, quinone reductase type 2 (QR2), has been identified in several mammalian species. QR2 is also capable of reducing quinones to hydroquinones, but unlike QR1, cannot use NAD(P)H. X-ray crystallographic studies of QR1 and QR2 illustrate that despite their different biochemical properties, these enzymes have very similar three-dimensional structures. In particular, conserved features of the active sites point to the close relationship between these two enzymes.
Insights
Mammalian quinone metabolism causes oxidative stress. NAD(P)H:quinone oxidoreductase type 1 (QR1) and QR2 enzymes reduce quinones, preventing radical production and toxicity. Structural similarities highlight their close relationship.
Area of Science:
- Biochemistry
- Molecular Biology
- Toxicology
Background:
- Quinone metabolism is a significant source of oxidative stress in mammals.
- Reactive oxygen species are by-products of many quinone metabolic pathways.
- NAD(P)H:quinone oxidoreductase type 1 (QR1) is a key enzyme in detoxifying quinones.
Purpose of the Study:
- To investigate the enzymatic mechanisms and structural relationships of quinone metabolizing enzymes.
- To understand the role of QR1 and QR2 in mitigating quinone toxicity.
Main Methods:
- Comparative biochemical analysis of QR1 and QR2.
- X-ray crystallography to determine enzyme structures.
- Assessment of enzyme activity in quinone reduction.
Main Results:
- QR1 utilizes NAD(P)H for a two-electron reduction of quinones, preventing radical formation.
- QR2 reduces quinones but does not use NAD(P)H.
- X-ray crystallography revealed highly similar three-dimensional structures for QR1 and QR2, particularly in their active sites.
Conclusions:
- QR1 and QR2 are structurally related enzymes involved in quinone detoxification.
- Their conserved active site features underscore their evolutionary relationship.
- Understanding these enzymes is crucial for combating quinone-induced oxidative stress.