Characterization of Epidermal 12(S) and 12(R) Lipoxygenases
Lipoxygenases (LO) are a family of non-heme iron containing proteins that stereospecifically insert molecular oxygen into 1, 4-cis, cis-pentadiene containing polyunsaturated fatty acids’. They are generally classified according to their positional specificity of arachidonic acid oxygenation and cell specific expression pattern2.6. Lipoxygenase activity gives rise to a number of bioactive lipid products including leukotrienes, lipoxins and HETE’s (hydroxyeicosatetraenoic acid’s).7’8The major lipoxygenase forms include the neutrophil 5-LO, platelet 12-LO and reticulocyte 15LO.2’3’6’9 In recent years the lipoxygenase family has expanded by means of molecular cloning studies to include several new members. An e-12(S)LO (epidermal12(S)lipoxygenase) cDNA was cloned and functionally expressed and its gene isolated10’1. Two other lipoxygenases found in skin have also been cloned, a 15-LO in humans distinct from the reticulocyte enzyme4and a related phorbol ester inducible 8-LO enzyme in mouse skins. All of these lipoxygenases generate HETE metabolites of theS-stereo configuration. However, recently mammalian lipoxygenase cDNAs that generated 12(R) -HETE have been cloned and functionally expressed.12-14The epidermal 12(S) and 12-(R) lipoxygenases have yet to be characterized in any great detail.10,12-14Here, we characterize further the epidermal 12(S) and 12(R)-LO’s and attempt to elucidate the enzyme’s primary structural determinants controlling chirality of oxygen insertion.
KeywordsHydroxyeicosatetraenoic Acid Eicosatrienoic Acid Amino Acid Stretch Methyl Arachidonate Cell Specific Expression Pattern
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