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Active renal hexose transport. Structural requirements

A Kleinzeller, E M McAvoy, R D McKibbin

    Biochimica Et Biophysica Acta
    |August 4, 1980
    PubMed
    Summary
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    Rabbit renal cortex actively transports methyl beta-D-galactoside via a shared carrier with D-glucose and D-galactose. Structural analysis reveals specific hydroxyl group requirements for this active sugar transport.

    Area of Science:

    • Biochemistry
    • Renal Physiology
    • Membrane Transport

    Background:

    • Active transport of sugars is crucial for renal reabsorption.
    • Understanding the specificity of sugar transporters aids in drug development and disease research.

    Purpose of the Study:

    • To investigate the active transport of methyl beta-D-galactoside in rabbit renal cortex.
    • To define the structural requirements for sugar interaction with the renal transport carrier.
    • To compare renal sugar transport specificity with intestinal transport.

    Main Methods:

    • Studied active transport of methyl beta-D-galactoside and analogs in rabbit renal cortical slices.
    • Utilized kinetic analysis (Kt determination) and inhibition studies with various analogs.
    • Investigated the role of specific hydroxyl groups by synthesizing and testing modified sugar analogs.

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    Main Results:

    • Methyl beta-D-galactoside accumulates against a concentration gradient, indicating active transport.
    • Transport is Na+-dependent and inhibited by dinitrophenol, phlorizin, and ouabain, suggesting dual pathways.
    • Structural analysis revealed a mandatory pyranose ring and preference for D-gluco configuration; hydroxyls at C1-C4 are important for affinity, while C6 hydroxyl is required for transport but not binding.

    Conclusions:

    • The renal carrier for D-glucose, D-galactose, and their methyl glycosides shares structural specificities with intestinal transporters.
    • Specific hydroxyl group interactions dictate substrate affinity and transport efficacy.
    • Dual transport mechanisms may be involved in renal sugar uptake.