Polymerizable phosphatidylcholines: importance of phospholipid motions for optimum phospholipase A2 and C activity.

Cross-linkable short-chain phosphatidylcholines with thiols at the chain terminus have been synthesized and characterized. These micelle-forming species were used to investigate two water-soluble phospholipases. When reduced, the thiol lipids were excellent substrates for phospholipase A2. Once cross-linked, they became extremely poor substrates. This is consistent with a mechanism in which a key step is the partial extraction of the substrate phosphatidylcholine from an aggregate. In contrast, phospholipase C activity was slightly enhanced if the product diglyceride was tethered to the aggregate through disulfide formation. For this enzyme such a kinetic effect is consistent with the hydrophobic diglyceride biasing the enzyme to the interface.