How Does ATP Regulate Erythrocyte Glucose Transport?: a Dissertation
Authors
Leitch, Jeffry M.Faculty Advisor
Dr. Anthony CarruthersAcademic Program
Biochemistry and Molecular PharmacologyUMass Chan Affiliations
Biochemistry and Molecular PharmacologyDocument Type
Doctoral DissertationPublication Date
2007-06-05Keywords
Erythrocytes3-O-Methylglucose
Adenosine Triphosphate
Glucose
Glucose Transporter Type 1
Carbohydrates
Cells
Hemic and Immune Systems
Heterocyclic Compounds
Nucleic Acids, Nucleotides, and Nucleosides
Metadata
Show full item recordAbstract
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.DOI
10.13028/s1m5-1b80Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31652Rights
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10.13028/s1m5-1b80