SYNTHESIS OF CHIRAL LIPIDS. APPLICATIONS TO THE SPECIFICITIES OF LIPOLYTIC ENZYMES.

Persistent Link:
http://hdl.handle.net/10150/187653
Title:
SYNTHESIS OF CHIRAL LIPIDS. APPLICATIONS TO THE SPECIFICITIES OF LIPOLYTIC ENZYMES.
Author:
KANDA, PATRICK.
Issue Date:
1984
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
In this study, synthetic routes to certain short acyl chain phospholipids were developed. Their inhibitory or substrate properties for phospholipase A₂ were then examined. An improved method for the acylation of glycerophosphocholine is described using a mixed fatty acid - trifluoroacetic acid anhydride. This partial synthetic route is particularly suitable for obtaining short acyl chain phosphatidylcholines. A new pathway for constructing the unnatural sn-1-phosphatidylcholines is also described, starting from L-arabinose. This is converted first to a key intermediate, 2,3-O-isopropylidene-sn-glycerol, which is then phosphorylated and transformed into sn-glycero-1-phosphocholine. This can be acylated as above to give sn-1-phosphatidylcholines. Routes to the short chain phosphatidylethanolamines were investigated and discussed. A procedure, using phospholipase D, was used to convert L-diC₆ PC into L-diC₆ PE in a transphosphatidylation reaction. Failed attempts to obtain shorter chain homologs by this and other methods are also detailed. The kinetics of inhibition of the phospholipase A₂ hydrolysis of L-diC₆ PC by the D-isomer are also reported for the monomeric concentration range. It was found that the D- enantiomer did not behave as a pure competitive inhibitor, and that an enzyme-substrate-inhibitor complex can exist. The implications of these results with regard to PLA₂ hydrolysis of mixed micelles is discussed. The PLA₂ substrate properties of both the anionic and zwitterionic diC₆ PE's were also studied. It was established that the anionic diC₆ PE is either a very poor substrate relative to the zwitterionic diC₆ PE, or acts as a competitive inhibitor towards its hydrolysis. Similarly, the rates of base-catalyzed acyl ester hydrolysis are about 18 times greater for the zwitterionic than for the anionic diC₆ PE. The importance of a protonated amino group in both these hydrolyses studies is noted. In addition, certain physical properties of diC₆ PE, such as its critical micelle concentration and carbon-13 NMR spectrum, are also given.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Organic compounds -- Synthesis.; Lipids.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Biochemistry; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Wells, Michael

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleSYNTHESIS OF CHIRAL LIPIDS. APPLICATIONS TO THE SPECIFICITIES OF LIPOLYTIC ENZYMES.en_US
dc.creatorKANDA, PATRICK.en_US
dc.contributor.authorKANDA, PATRICK.en_US
dc.date.issued1984en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractIn this study, synthetic routes to certain short acyl chain phospholipids were developed. Their inhibitory or substrate properties for phospholipase A₂ were then examined. An improved method for the acylation of glycerophosphocholine is described using a mixed fatty acid - trifluoroacetic acid anhydride. This partial synthetic route is particularly suitable for obtaining short acyl chain phosphatidylcholines. A new pathway for constructing the unnatural sn-1-phosphatidylcholines is also described, starting from L-arabinose. This is converted first to a key intermediate, 2,3-O-isopropylidene-sn-glycerol, which is then phosphorylated and transformed into sn-glycero-1-phosphocholine. This can be acylated as above to give sn-1-phosphatidylcholines. Routes to the short chain phosphatidylethanolamines were investigated and discussed. A procedure, using phospholipase D, was used to convert L-diC₆ PC into L-diC₆ PE in a transphosphatidylation reaction. Failed attempts to obtain shorter chain homologs by this and other methods are also detailed. The kinetics of inhibition of the phospholipase A₂ hydrolysis of L-diC₆ PC by the D-isomer are also reported for the monomeric concentration range. It was found that the D- enantiomer did not behave as a pure competitive inhibitor, and that an enzyme-substrate-inhibitor complex can exist. The implications of these results with regard to PLA₂ hydrolysis of mixed micelles is discussed. The PLA₂ substrate properties of both the anionic and zwitterionic diC₆ PE's were also studied. It was established that the anionic diC₆ PE is either a very poor substrate relative to the zwitterionic diC₆ PE, or acts as a competitive inhibitor towards its hydrolysis. Similarly, the rates of base-catalyzed acyl ester hydrolysis are about 18 times greater for the zwitterionic than for the anionic diC₆ PE. The importance of a protonated amino group in both these hydrolyses studies is noted. In addition, certain physical properties of diC₆ PE, such as its critical micelle concentration and carbon-13 NMR spectrum, are also given.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectOrganic compounds -- Synthesis.en_US
dc.subjectLipids.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineBiochemistryen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorWells, Michaelen_US
dc.identifier.proquest8412670en_US
dc.identifier.oclc690920589en_US
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