Advances in the stereoselective synthesis of antifungal agents and ...

Chapter 2 552.2.4 Lipases.Most lipases are classified as serine proteases which catalyze thehydrolysis of lipids to fatty acids and glycerol 31 . Unlike esterases, whichshow a normal Michaelis Menten behaviour, lipases display only littleactivity in aqueous solutions in presence of soluble substrates. A sharpincrease in activity is observed when the substrate concentration isincreased beyond its critical micellar concentration 32a-c . The increased lipaseactivity at the lipid-water interface led to the suggestion that soluble lipasesmight undergo a conformational change -interfacial activation- at the oilwater interface 33 . This conformational change at the interface is supportedby the X-Ray structures of human 34a,b and Mucor miehei 35a-c lipases,phospholipase A 236a-b and their complexes with inhibitors where the shift ofa loop called "lid" over the active site is clearly shown.RCO 2 H + Enz-OHRCO 2 R' + Enz-OHROHO-Enz- R'OHH 2 OOa) ester hydrolysisb) esterificationc) transterificationOR'ROEnztetrahedral intermediateR"OHd) acyl transferRCO 2 R" + Enz-OHFigure 2.10: The four reactions catalyzed by ester hydrolasesGenerally lipases catalyze four different reactions involving carboxylicesters (figure 2.10):a) Ester hydrolysisb) Esterificationc) Transesterificationd) Acyl transferAlthough not in all cases proven beyond doubt, it is generally acceptedthat the catalytic mechanisms are similar to those of serine proteases whichhave been studied in great detail.