title: The effect of retinol and retinoic acids on lipoxygenase activity.
abstract: Lipoxygenase catalyzes the dioxygenation of polyenoic fatty acids such as linoleate and arachidonate. The aim of the present study was to examine the effect of retinol, all-trans-retinoic acid and 13-cis-retinoic acid on the activity of lipoxygenase-1 and lipoxygenase-2 towards linoleic acid. Lipoxygenase activity toward linoleic acid was followed by determining changes in absorption at 234 nm. All retinoids inhibited lipoxygenase-1 and lipoxygenase-2 activity. Lipoxygenase-2 activity towards linoleic acid was rapid at pH 6.5; all-trans-retinol (10 microM) caused a 50% inhibition in reaction rate. All-trans-retinol was oxidized in parallel with diene production by lipoxygenase-2. Lipoxygenase-2 activity on linoleic acid was competitively inhibited by all-trans-retinol and all-trans-retinoic acid; 13-cis-retinoic acid exhibited mixed type inhibition. Activity of lipoxygenase-1 towards linoleic acid at pH 9.0 was also inhibited by retinoic acids by 32-73%. All-trans-retinoic acid and 13-cis-retinoic acid inhibited lipoxygenase-1 activity competitively, whereas all-trans-retinol inhibited lipoxygenase-1 activity in a mixed manner. These findings suggest that retinoids may bind to the active site of the enzyme or simultaneously act as an antioxidant.
authors.affiliation: Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Goldreich
authors.forename: S
authors.initials: S
authors.lastname: Grossman
authors.forename: Y
authors.initials: Y
authors.lastname: Sofer
authors.forename: E
authors.initials: E
authors.lastname: Breitbart
authors.forename: D
authors.initials: D
authors.lastname: Sklan
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015474:Isotretinoin / Q000494:pharmacology; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D013025:Glycine max / Q000201:enzymology; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008041:Linoleic Acids; D016859:Lipoxygenase Inhibitors; D014801:Vitamin A; D014212:Tretinoin; D019787:Linoleic Acid; D008084:Lipoxygenase; D015474:Isotretinoin