PMID: 2505853Sep 25, 1989Paper

Metabolism of unsaturated fatty acids by RBL-1 5-lipoxygenase: influence of substrate solubility and product inactivation

Biochimica Et Biophysica Acta
R M McMillanV N Jacobs

Abstract

Several alternative fatty acid substrates have been employed to characterise the kinetics of rat basophilic leukaemia cell (RBL-1) 5-lipoxygenase. Using arachidonic acid (AA) as substrate, enzymes rates declined at high substrate concentrations (greater than 25 microM) and were associated with pronounced lag phases. The concentrations of AA at which apparent substrate inhibition and lag phases were observed were comparable with those at which AA induced emulsion formation in aqueous media. No evidence for substrate inhibition or lag phases was observed using eicosapentaenoic acid (EPA), a more soluble substrate which did not induce emulsion formation at concentrations up to 100 microM. Reactions catalysed by RBL-1 5-lipoxygenase terminated before exhaustion of substrate. AA and EPA induced time-dependent enzyme inactivation at concentrations 100-fold lower than their apparent Km values for the enzyme. The ability of several fatty acids to induce time-dependent inactivation was directly proportional to their substrate potency. We conclude that apparent substrate inhibition is a consequence of a change from monomeric to micellar substrate which has a lower affinity for the enzyme and that premature termination of the enzyme react...Continue Reading

References

Mar 1, 1986·Prostaglandins·M T SkoogJ S Wiseman
Feb 1, 1988·Biological Chemistry Hoppe-Seyler·M Haurand, L Flohé
Sep 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C A Rouzer, B Samuelsson
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Aug 1, 1980·Prostaglandins·B A JakschikP Needleman
Feb 1, 1984·Prostaglandins·T TeranoS Moncada
Mar 15, 1984·European Journal of Biochemistry·S RapoportG Hausdorf
Jan 1, 1984·Prostaglandins, Leukotrienes, and Medicine·W E Lands
Aug 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Steven D Allison, Jennifer B H Martiny

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