Show simple item record

dc.contributor.advisorDr. Anthony Carruthers
dc.contributor.authorLeitch, Jeffry M.
dc.date2022-08-11T08:08:41.000
dc.date.accessioned2022-08-23T16:04:14Z
dc.date.available2022-08-23T16:04:14Z
dc.date.issued2007-06-05
dc.date.submitted2007-09-10
dc.identifier.doi10.13028/s1m5-1b80
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31652
dc.description.abstractHuman erythrocyte glucose sugar transport displays a complexity that is not explained by available models. Sugar transport was examined in resealed red cell ghosts under equilibrium exchange conditions (intracellular [sugar] = extracellular [sugar]). Exchange 3-O-methylglucose (3MG) import and export are monophasic in the absence of cytoplasmic ATP but are biphasic when ATP is present. Biphasic exchange is observed as the rapid filling of a large compartment (66% cell volume) followed by the slow filling of the remaining cytoplasmic space. Two models for biphasic sugar transport are presented in which 3MG must overcome a sugar-specific, physical (diffusional) or chemical (anomerization) barrier to equilibrate with cell water. The anomerization model was rejected through several lines of direct experimental investigation. 1) The sizes of the fast and slow phases of sugar transport do not correlate with the equilibrium anomer distributions of all GLUT1 sugar substrates. 2) Increasing the rate of anomerization by addition of exogenous intracellular mutarotase has no effect on biphasic transport kinetics. 3) Direct measurement of initial rates of sugar uptake or exchange demonstrates that GLUT1 shows no anomer preference. The physical barrier model was further refined by the use of the counterflow condition (intracellular [sugar] >> extracellular [sugar]). The presence of a physical barrier alone was unable to explain the complex counterflow time courses observed. As a result, the model was modified to include the action of a specific sugar export that is compartmentalized from rapidly equilibrating, GLUT1-mediated uptake and exit.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectErythrocytes
dc.subject3-O-Methylglucose
dc.subjectAdenosine Triphosphate
dc.subjectGlucose
dc.subjectGlucose Transporter Type 1
dc.subjectCarbohydrates
dc.subjectCells
dc.subjectHemic and Immune Systems
dc.subjectHeterocyclic Compounds
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.titleHow Does ATP Regulate Erythrocyte Glucose Transport?: a Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1335&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/335
dc.legacy.embargo2017-04-24T00:00:00-07:00
dc.identifier.contextkey364142
refterms.dateFOA2022-08-25T05:03:35Z
html.description.abstract<p>Human erythrocyte glucose sugar transport displays a complexity that is not explained by available models. Sugar transport was examined in resealed red cell ghosts under equilibrium exchange conditions (intracellular [sugar] = extracellular [sugar]). Exchange 3-O-methylglucose (3MG) import and export are monophasic in the absence of cytoplasmic ATP but are biphasic when ATP is present. Biphasic exchange is observed as the rapid filling of a large compartment (66% cell volume) followed by the slow filling of the remaining cytoplasmic space. Two models for biphasic sugar transport are presented in which 3MG must overcome a sugar-specific, physical (diffusional) or chemical (anomerization) barrier to equilibrate with cell water. The anomerization model was rejected through several lines of direct experimental investigation. 1) The sizes of the fast and slow phases of sugar transport do not correlate with the equilibrium anomer distributions of all GLUT1 sugar substrates. 2) Increasing the rate of anomerization by addition of exogenous intracellular mutarotase has no effect on biphasic transport kinetics. 3) Direct measurement of initial rates of sugar uptake or exchange demonstrates that GLUT1 shows no anomer preference. The physical barrier model was further refined by the use of the counterflow condition (intracellular [sugar] >> extracellular [sugar]). The presence of a physical barrier alone was unable to explain the complex counterflow time courses observed. As a result, the model was modified to include the action of a specific sugar export that is compartmentalized from rapidly equilibrating, GLUT1-mediated uptake and exit.</p>
dc.identifier.submissionpathgsbs_diss/335
dc.contributor.departmentBiochemistry and Molecular Pharmacology
dc.description.thesisprogramBiochemistry and Molecular Pharmacology


Files in this item

Thumbnail
Name:
Leitch_Jeffry.pdf
Size:
8.282Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record