Aconitase is rapidly inactivated by \(2 R, 3 R\) -fluorocitrate, which is
produced from fluoroacetate in the citrate synthase reaction. Interestingly,
inactivation by fluorocitrate is accompanied by stoichiometric release of
fluoride ion (i.e., one F-ion is lost per aconitase active site \() .\) This
observation is consistent with "mechanism-based inactivation" of aconitase by
fluorocitrate. Suggest a mechanism for this inactivation, based on formation
of 4 -hydroxy-trans-aconitate, which remains tightly bound at the active site.
To assess your answer, consult this reference: Lauble, H., Kennedy, M., et
al., 1996. The reaction of fluorocitrate with aconitase and the crystal
structure of the enzyme-inhibitor complex. Proceedings of the National Academy
of Sciences \(93: 13699-13703\)