Inhibition of soybean lipoxygenase 1 by N-alkylhydroxylamines

Abstract

Micromolar concentrations of N-octylhydroxylamine dramatically increase the induction period in the conversion of linoleic acid to 13(S)-hydroperoxy-cis-9,trans-11-octadecadienoic acid (13-HPOD) catalyzed by soybean lipoxygenase 1. The induction period produced by N-octylhydroxylamine is abolished by 13-HPOD but not by the corresponding hydroxy acid. Addition of a catalytic amount of lipoxygenase to a mixture of 13-HPOD and N-octylhydroxylamine results in consumption of approximately 1 mumol of 13-HPOD/mumol of N-octylhydroxylamine present. These results can be explained by a model in which 13-HPOD oxidizes the enzyme from an inactive ferrous form to an active ferric form, as proposed by previous workers, and N-octylhydroxylamine reduces the enzyme back to the ferrous form. Consistent with this model, the ESR signal at g = 6.1 characteristic of ferric lipoxygenase is rapidly abolished by N-octylhydroxylamine and can be regenerated by 13-HPOD. These results provide additional support for earlier proposals that ferric lipoxygenase is the catalytically active form and also establish a novel method of inhibiting enzymes in this class. The octyl group of N-octylhydroxylamine appears to contribute to binding near the iron, since hydroxylamine and N-methylhydroxylamine do not extend the induction period. In the n-RNHOH series, activity passes through an optimum at R = decyl.

Evaluation of Antibacterial, Antifungal, Enzyme Inhibition and Hemolytic Activities of Caryopteris Odorata Fractions

“…Hence, the search for new cholinesterase inhibitors is considered to be an important and ongoing strategy to introduce new drug candidates for the treatment of Alzheimer's disease and other related diseases 25 . Lipoxygenases catalyze the addition of molecular oxygen to fatty acids containing a cis-1, 4-pentadiene system to give unsaturated fatty acid hydro peroxide 26,27 . It has been found that these LOX products play a key role in variety of disorders such as bronchial asthma, inflammation 28 and tumor angiogenesis 29 .…”

Screening of <i>Ranunculus sceleratus</i> for enzyme inhibition, antibacterial and antioxidant activities

“…Often the most effective treatments are ligands which inhibit the breakdown of acetylcholine. Lipoxygenases catalyze the addition of molecular oxygen to fatty acids containing a cis-1, 4-pentadiene system to give unsaturated fatty acid hydro peroxide (Clapp et al, 1985). It has been found that these lipoxygenase products play a key role in variety of disorders such as bronchial asthma, inflammation and tumor angiogenesis.…”

Preliminary structure-activity relationship studies on some novel s-substituted aliphatic analogues of 5-{1-[(4- chlorophenyl) sulfonyl]-3-piperidinyl}-1, 3, 4-oxadiazol-2-yl sulfide

“…Lipoxygenase activity was assayed using the methods as described previously [17,18], with slight modifications. A total volume of 200 μL assay mixture contained 150 μL sodium phosphate buffer (100 mM, pH 8.0), 10 μL test compound and 15 μL purified lipoxygenase (Sigma, USA).…”