Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2
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 a...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
1988-10-01
|
Series: | Journal of Lipid Research |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520384406 |
id |
doaj-afc776b3b2954f13b519e3ba064b2fa1 |
---|---|
record_format |
Article |
spelling |
doaj-afc776b3b2954f13b519e3ba064b2fa12021-04-25T04:19:12ZengElsevierJournal of Lipid Research0022-22751988-10-01291012971308Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2M D Lister0A J Hancock1Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110.Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 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.http://www.sciencedirect.com/science/article/pii/S0022227520384406 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
M D Lister A J Hancock |
spellingShingle |
M D Lister A J Hancock Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2 Journal of Lipid Research |
author_facet |
M D Lister A J Hancock |
author_sort |
M D Lister |
title |
Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2 |
title_short |
Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2 |
title_full |
Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2 |
title_fullStr |
Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2 |
title_full_unstemmed |
Cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase A2 |
title_sort |
cyclopentanoid analogs of phosphatidylcholine: susceptibility to phospholipase a2 |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
1988-10-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520384406 |
work_keys_str_mv |
AT mdlister cyclopentanoidanalogsofphosphatidylcholinesusceptibilitytophospholipasea2 AT ajhancock cyclopentanoidanalogsofphosphatidylcholinesusceptibilitytophospholipasea2 |
_version_ |
1721510480210558976 |