Title : Irreversible inactivation of 5-lipoxygenase by leukotriene A4. Characterization of product inactivation with purified enzyme and intact leukocytes.

Pub. Date : 1994 Jan 28

PMID : 8300592






7 Functional Relationships(s)
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1 Irreversible inactivation of 5-lipoxygenase by leukotriene A4. Leukotriene A4 arachidonate 5-lipoxygenase Homo sapiens
2 We report that leukotriene A4, the electrophilic product of 5-lipoxygenase catalysis, irreversibly inactivates the enzyme. Leukotriene A4 arachidonate 5-lipoxygenase Homo sapiens
3 Leukotriene A4 inactivates cellular 5-lipoxygenase without inhibiting its translocation from the cytosol to the membrane, suggesting that it impairs catalysis without impairing formation of the complex between 5-lipoxygenase and its membrane-associated activating protein. Leukotriene A4 arachidonate 5-lipoxygenase Homo sapiens
4 Leukotriene A4 inactivates cellular 5-lipoxygenase without inhibiting its translocation from the cytosol to the membrane, suggesting that it impairs catalysis without impairing formation of the complex between 5-lipoxygenase and its membrane-associated activating protein. Leukotriene A4 arachidonate 5-lipoxygenase Homo sapiens
5 Consistent with this, leukotriene A4 inactivates purified 5-lipoxygenase from human neutrophils, via saturable, pseudo first-order kinetics with a rate constant, ki = 0.14 min-1 and a dissociation constant, Ki = 2.1 +/- 0.7 microM. Leukotriene A4 arachidonate 5-lipoxygenase Homo sapiens
6 Preincubation with leukotriene A4 diminished the incorporation of radiolabeled material, consistent with irreversible modification of 5-lipoxygenase by its metastable product, leukotriene A4. Leukotriene A4 arachidonate 5-lipoxygenase Homo sapiens
7 Preincubation with leukotriene A4 diminished the incorporation of radiolabeled material, consistent with irreversible modification of 5-lipoxygenase by its metastable product, leukotriene A4. Leukotriene A4 arachidonate 5-lipoxygenase Homo sapiens