Interaction of sheep liver cytosolic aldehyde dehydrogenase with quercetin, resveratrol and diethylstilbestrol

• Published in: Chemico-biological interactions Vol. 130; no. 1-3; pp. 57 - 69
• Main Authors: Kitson, Trevor M, Kitson, Kathryn E, Moore, Stanley A
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 30-01-2001
• Subjects: Aldehyde dehydrogenase; Aldehyde Dehydrogenase - antagonists & inhibitors; Aldehyde Dehydrogenase - chemistry; Aldehyde Dehydrogenase - metabolism; Animals; Binding Sites; Catalytic Domain; Cytosol - enzymology; Diethylstilbestrol; Diethylstilbestrol - metabolism; Diethylstilbestrol - pharmacology; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; In Vitro Techniques; Kinetics; Liver - enzymology; Models, Molecular; NAD - metabolism; Protein Conformation; Quercetin; Quercetin - chemistry; Quercetin - metabolism; Quercetin - pharmacology; Resveratrol; Sheep; Stilbenes - metabolism; Stilbenes - pharmacology; Diethylstilbestrol; Aldehyde dehydrogenase; Quercetin; Resveratrol
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/S0009-2797(00)00222-2

The effects of quercetin and resveratrol (substances found in red wine) on the activity of cytosolic aldehyde dehydrogenase in vitro are compared with those of the synthetic hormone diethylstilbestrol. It is proposed that quercetin inhibits the enzyme by binding competitively in both the aldehyde substrate binding-pocket and the NAD
+-binding site, whereas resveratrol and diethylstilbestrol can only bind in the aldehyde site. When inhibition is overcome by high aldehyde and NAD
+ concentrations (1 mM of each), the modifiers enhance the activity of the enzyme; we hypothesise that this occurs through binding to the enzyme-NADH complex and consequent acceleration of the rate of dissociation of NADH. The proposed ability of quercetin to bind in both enzyme sites is supported by gel filtration experiments with and without NAD
+, by studies of the esterase activity of the enzyme, and by modelling the quercetin molecule into the known three-dimensional structure of the enzyme. The possibility that interaction between aldehyde dehydrogenase and quercetin may be of physiological significance is discussed.