dc.contributor.advisor |
Dr Roy Geddes |
en |
dc.contributor.author |
Taylor, Jacqueline Ann |
en |
dc.contributor.author |
O'Flaherty, Jackie (name change) |
en |
dc.date.accessioned |
2008-02-27T02:04:05Z |
en |
dc.date.available |
2008-02-27T02:04:05Z |
en |
dc.date.issued |
1985 |
en |
dc.identifier.citation |
Thesis (PhD--Biochemistry)--University of Auckland, 1985. |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/2380 |
en |
dc.description |
Restricted Item. Print thesis available in the University of Auckland Library or may be available through Interlibrary Loan. |
en |
dc.description.abstract |
Although glycogen is a chemically homogeneous material it is polydisperse, exhibiting a broad molecular weight spectrum and a metabolic lability that is molecular weight dependent. The lower molecular weight (β-particle) glycogen was found to be extremely labile, while the higher molecular weight (α-particle) exhibited a far lower metabolic activity, indicating that it may act as a glycogen store for mobilisation in stress situations. These observations, coupled to the existence of Pompe’s Disease, a glycogen storage disease involving the lysosomal system, supports the hypothesis that α - and β -particulate glycogen may be partially separated from one another within the cell i.e. compartmentalised. By the use of a rapid differential centrifugation technique it was possible to show, both physiochemically and ultrastructurally, the existence of glycogen of a very large molecular size associated with the lysosomal fraction. This glycogen exhibited a different molecular weight distribution from that isolate from the liver as a whole i.e. cytosol + lysosomal. It is suggested that appreciably more than 10% of cellular glycogen is located within the lysosomes and that this is of predominantly high molecular weight. The size-distribution of liver glycogen was shown to be distinctly affected by the anti-inflammatory drugs, salicylate and Indomethacin. By measurement of the incorporation of radioactive glucose into glycogen, salicylate was shown to have a depressing effect on overall liver glycogen metabolism. These effects appear to arise from a stabilisation of the lysosomal membrane by the drugs. The incorporation, via liposomes, of purified anti-1,4-α-glucosidase antibodies into the liver lysosomes of normal Wistar rats and rats with a genetic deficiency of phosphorylase kinase, caused a distinct decrease in 1,4-α-glucosidase activity and in the content of high molecular weight glycogen. These changes were enhanced by prolonged liposomal-antibody treatment and suggested that a possible feedback control mechanism operates in the incorporation of glycogen into lysosomes. The 1-4- α -glucosidase inhibitor, Acarbose, when injected intraperitoneally into normal and phosphorylase kinase-deficient rats similarly disturbed liver lysosomal metabolism, causing distinct and persistent inhibition of enzymes and acute disturbances of lysosomal glycogen metabolism. Again a feedback control mechanism appears to operate, which effects cytosolic carbohydrate metabolism. The biochemical effects closely resembled those occurring in Pompe’s disease and were confirmed by electron microscopy. A model for the adult form of the lysosomal storage disease has been suggested. |
en |
dc.format |
Scanned from print thesis |
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dc.language.iso |
en |
en |
dc.publisher |
ResearchSpace@Auckland |
en |
dc.relation.ispartof |
PhD Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA98551 |
en |
dc.rights |
Whole document restricted. Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Factors affecting the metabolic control of cytosolic and lysosomal glycogen levels in the liver |
en |
dc.type |
Thesis |
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thesis.degree.discipline |
Biochemistry |
en |
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Doctoral |
en |
thesis.degree.name |
PhD |
en |
dc.subject.marsden |
Fields of Research::270000 Biological Sciences::270100 Biochemistry and Cell Biology |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.local.anzsrc |
0601 - Biochemistry and Cell Biology |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/ClosedAccess |
en |
pubs.org-id |
Faculty of Science |
en |
dc.identifier.wikidata |
Q112848714 |
|