Positional specificity of lipoxygenases and their suitability for testing potential drugs.
Comparative studies on isolated lipoxygenases revealed the following features: variability of their positional specificity, diversity of enzymatic properties including sensitivity to inhibitors, a common general mechanism of action. The molecular basis of the positional specificity of lipoxygenases is discussed. The lipoxygenase of reticulocytes proved to be an excellent model in the search for inhibitors of the arachidonate 5-lipoxygenase. Reticulocyte lipoxygenase may form a wide spectrum of products belonging to all important classes of primary lipoxygenase metabolites hitherto known (HPETE's, diHPETE's, lipoxins, epoxyleukotrienes and others). This enzyme was used as basal test in a screening hierarchy for lipoxygenase-inhibitory antiasthmatic drugs and led to the discovery of new orally acting potential antiasthmatics. There was a high correlation between inhibition of reticulocyte lipoxygenase and antibronchoconstrictory activity with airway preparations in vitro and in vivo.
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D008084:Lipoxygenase / Q000502:physiology*; D016859:Lipoxygenase Inhibitors; D012156:Reticulocytes / Q000201:enzymology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D016859:Lipoxygenase Inhibitors; D008084:Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase