Polychlorinated biphenyls and related metabolites : mode of action on phospholipid and glyceride biosynthesis Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/t722hc425

Descriptions

Attribute NameValues
Creator
Abstract or Summary
  • Polychlorinated biphenyls (PCBs) have been reported to cause alterations in the metabolism of phospholipids and glycerides in animals and humans. This project was undertaken in an attempt to determine the mode of action of PCBs and their primary metabolites on phospholipid and glyceride biosynthesis. The activity of sn-glycerol-3 phosphate acyltransferase was inhibited by PCBs in vitro. The inhibition was noncompetitive suggesting a binding to a site other than the active site on the enzyme. The inhibition of the activity of this enzyme was accompanied by a general decline in the in vitro synthesis of phospholipids by microsomes, mitochondria and cell-free homogenates. Glyceride synthesis by mitochondria and cell-free homogenates decreased while it increased in the microsomes. After in vivo treatment of rats with PCB for 30 days, the activity of microsomal sn-glycerol-3 phosphate acyltransferase declined. The decline in enzyme activity was accompanied by a decreased incorporation of radioactivity into microsomal phospholipids and glycerides. On the other hand, mitochondria and cell-free homogenates consistently showed apparent increases in the incorporation of radioactivity into phospholipids and glycerides after the PCB treatment. The purified isomer, 2,4,5,2',4',5'-hexachlorobiphenyl elicited the same kind of response as the commercial PCB preparation. It inhibited the activity of sn-glycerol-3 phosphate acyltransferase which caused a decrease in the synthesis of phospholipids in vitro. Glyceride synthesis again increased in microsomes but decreased in the cell-free homogenate. The in vitro activities of glycerol kinase and diglyceride acyltransferase were not affected by PCB at concentrations as high as 1.5 mM. This concentration was more than three times that needed to inhibit sn-glycerol-3 phosphate acyltransferase. Microsomal phosphatidate phosphatase activity was not affected during the initial stages of catalysis, but after prolonged incubation, there was a small increase (22 percent) or decrease (18 percent) in the activity under in vitro and in vivo conditions, respectively. The slight increase in the activity of this enzyme under the in vitro conditions was observed at 1.2 mM PCB which was more than two times that at which sn-glycerol-3 phosphate acyltransferase is significantly inhibited. The activity of phosphorylcholine-glyceride transferase was inhibited at 1.5 mM PCB in vitro but the inhibition was much less than observed with sn-glycerol-3 phosphate acyltransferase. Two primary metabolites of PCB, 4'-chloro-4-biphenylol and 2',3',4',5,5'-pentachloro-2-biphenylol elicited the same kind of response as PCBs in vitro. Both compounds inhibited the activity of sn-glycerol-3 phosphate acyltransferase, with large decreases in the in vitro synthesis of phospholipids by microsomes, mitochondria, and cell-free homogenates. Glyceride synthesis by mitochondria and homogenates also decreased, but increased in the microsomes. The pentachlorobiphenylol was a more potent inhibitor of the activity of sn-glycerol-3 phosphate acyltransferase than PCBs. The inhibition of the enzyme by this compound was also noncompetitive. The 4'-chloro-4- biphenylol did not affect the activity of microsomal phosphatidate phosphatase, but the pentachlorobiphenylol slightly stimulated the enzyme activity (25 percent). The latter observation might in part account for the increased glyceride synthesis observed in the microsomes. The overall results are consistent with the conclusion that PCBs and their metabolites inhibit phospholipid and glyceride synthesis at the site of the reaction catalyzed by sn-glycerol-3 phosphate acyltransferase. A model is proposed in this project which accounts for all the observed results and is consistent with the conclusion drawn.
Resource Type
Date Available
Date Copyright
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Academic Affiliation
Non-Academic Affiliation
Subject
Rights Statement
Peer Reviewed
Language
Digitization Specifications
  • File scanned at 300 ppi (Monochrome) using ScandAll PRO 1.8.1 on a Fi-6670 in PDF format. CVista PdfCompressor 4.0 was used for pdf compression and textual OCR.
Replaces
Additional Information
  • description.provenance : Submitted by Katy Davis (kdscannerosu@gmail.com) on 2013-10-07T19:38:44Z No. of bitstreams: 1 DzogbefiaVictoriaP1979.pdf: 1352847 bytes, checksum: f76a0431a9b6a636862695b0fdb7c4c4 (MD5)
  • description.provenance : Made available in DSpace on 2013-10-07T21:14:32Z (GMT). No. of bitstreams: 1 DzogbefiaVictoriaP1979.pdf: 1352847 bytes, checksum: f76a0431a9b6a636862695b0fdb7c4c4 (MD5) Previous issue date: 1979-04-24
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2013-10-07T20:07:09Z (GMT) No. of bitstreams: 1 DzogbefiaVictoriaP1979.pdf: 1352847 bytes, checksum: f76a0431a9b6a636862695b0fdb7c4c4 (MD5)
  • description.provenance : Approved for entry into archive by Deborah Campbell(deborah.campbell@oregonstate.edu) on 2013-10-07T21:14:32Z (GMT) No. of bitstreams: 1 DzogbefiaVictoriaP1979.pdf: 1352847 bytes, checksum: f76a0431a9b6a636862695b0fdb7c4c4 (MD5)

Relationships

Parents:

This work has no parents.

Last modified

Downloadable Content

Download PDF

Items