Journal of Lipid Research, Vol 29, 1297-1308, Copyright © 1988 by Lipid Research, Inc.
Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2
MD Lister and AJ Hancock
Department of Chemistry, University of Missouri-Kansas City 64110.
Six isomers of dipalmitoylcyclopentanetriol phosphocholine
(cyclopentano-lecithin) were tested as potential substrates for
phospholipase A2. Since each of these analogs possesses a configuration
that mimics a narrow range of conformations of a glycerophospholipid
molecule, the analogs were used to assess the enzyme's conformational
requirements. Studies showed that all of the analogs containing the
phosphocholine at the C-1 (or C-3) position could be hydrolyzed, while only
one of the three analogs that contains the polar head group at the C-2
position was susceptible. Kinetic studies, however, revealed that only the
all-trans-(1,3/2-1P)-cyclopentano-lecithin gave initial rates of hydrolysis
that were measurable by pH-stat. Acyl group specificity of the enzyme
towards the all-trans isomer was determined with an analog was acyl groups
were distinguishable. The synthesis of this mixed-acid-cyclopentano-PC is
described herein. When this analog was enzymatically assayed, results
unequivocally showed the enzyme to be specific for C-2 acyl hydrolysis.
This specificity, and data showing that the all-trans analog is
stereospecifically hydrolyzed, indicate that it is acted on in an analogous
manner to dipalmitoylphosphatidylcholine. These studies indicate that
although the configuration of the analog is not necessarily a prerequisite
for hydrolysis, there does appear to be an optimal spatial orientation for
enzymatic activity. The analogy between the susceptibilities of all-
trans-(1,3/2-1P)-cyclopentano-lecithin and glycero-lecithin suggests that
the conformation of the glycero-lecithin during phospholipase A2- mediated
hydrolysis may be best simulated by the all-trans orientation of C-O bonds
in the artificial substrate.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
