The effect of retinol and retinoic acids on lipoxygenase activity.
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.
Goldreich
D
D
Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Grossman
S
S
Sofer
Y
Y
Breitbart
E
E
Sklan
D
D
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*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008041:Linoleic Acids; D016859:Lipoxygenase Inhibitors; D014801:Vitamin A; D014212:Tretinoin; D019787:Linoleic Acid; D008084:Lipoxygenase; D015474:Isotretinoin