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• W1997347515 endingPage "93" @default.
• W1997347515 startingPage "83" @default.
• W1997347515 abstract "The lipoxygenases (LOs) are a family of nonheme iron dioxygenases that catalyse the insertion of molecular oxygen into polyunsaturated fatty acids. Five members of this gene family have been described in man, 5‐LO, 12 S ‐LO, 12 R ‐LO, 15‐LO and 15 S ‐LO. Using partially purified recombinant 15 S ‐LO enzyme and cells constitutively expressing this protein, we have compared the activity, substrate specificity, kinetic characteristics and regulation of this enzyme to that previously reported for 15‐LO. 15 S ‐LO has a threefold higher K m , similar V max and increased specificity of oxygenation for arachidonic acid, and a similar K m but decreased V max for linoleic acid in comparison to 15‐LO. Unlike 15‐LO, 15 S ‐LO is not suicide inactivated by the products of fatty acid oxygenation. However, in common with other LOs, 15 S ‐LO activity is regulated through calcium‐dependent association of the enzyme with the membrane fraction of cells. In addition, whilst independently cloning the recently described 15 S ‐LO, we identified a splice variant containing an in‐frame 87‐bp deletion corresponding to amino acids 401–429 inclusive. Modelling of the 15 S ‐LO and subsequent studies with partially purified recombinant protein suggest that the deleted region comprises a complete α‐helix flanking the active site of the enzyme resulting in decreased specificity of oxygenation and affinity for fatty acid substrates. Alternative splicing of 15 S ‐LO would therefore provide a further level of regulation of fatty acid metabolism. These results demonstrate that there are substantial differences in the enzyme characteristics and regulation of the 15‐LO isozymes which may reflect differing roles for the proteins in vivo ." @default.
• W1997347515 created "2016-06-24" @default.
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• W1997347515 date "1999-11-15" @default.
• W1997347515 modified "2023-10-17" @default.
• W1997347515 title "Differential characteristics of human 15-lipoxygenase isozymes and a novel splice variant of 15S-lipoxygenase" @default.
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• W1997347515 doi "https://doi.org/10.1046/j.1432-1327.1999.00818.x" @default.
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