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Structural requirements for binding to the sugar-transport system of the human erythrocyte.
- Source :
-
The Biochemical journal [Biochem J] 1973 Feb; Vol. 131 (2), pp. 211-21. - Publication Year :
- 1973
-
Abstract
- The structural requirements for binding to the glucose/sorbose-transport system in the human erythrocyte were explored by measuring the inhibition constants, K(i), for specifically substituted analogues of d-glucose when l-sorbose was the penetrating sugar. Derivatives in which a hydroxyl group in the d-gluco configuration was inverted, or replaced by a hydrogen atom, at C-1, C-2, C-3, C-4 or C-6 of the d-glucose molecule, all bound to the carrier, confirming that no single hydroxyl group is essential for binding to the carrier. The binding and transport of 1-deoxy-d-glucose confirmed that the sugars bind in the pyranose form. The relative inhibition constants of d-glucose and its deoxy, epimeric and fluorinated analogues are consistent with the combination of beta-d-glucopyranose with the carrier by hydrogen bonds at C-1, C-3, probably C-4, and possibly C-6 of the sugar. Both polar and non-polar substituents at C-6 enhance the affinity of d-glucose derivatives relative to d-xylose, and d-galactose derivatives relative to l-arabinose, and it is suggested that the carrier region around C-6 of the sugar may contain both hydrophobic and polar binding groups. The spatial requirements at C-1, C-2, C-3, C-4 and C-6 were explored by comparing the relative binding of d-glucose and its halogeno and O-alkyl substituents. The carrier protein closely approaches the sugar except at C-3 in the d-gluco configuration, C-4 and C-6. d-Glucal was a good inhibitor, showing that a strict chair form is not essential for binding. 3-O-(2',3'-Epoxypropyl)-d-glucose, a potential substrate-directed alkylating agent, bound to the carrier, but did not inactivate it.
- Subjects :
- Binding Sites
Biological Transport
Carbon Isotopes
Carrier Proteins metabolism
Chromatography, Paper
Chromatography, Thin Layer
Erythrocytes drug effects
Ethers, Cyclic metabolism
Glucose pharmacology
Humans
Kinetics
Mathematics
Models, Biological
Molecular Conformation
Protein Conformation
Sorbose pharmacology
Structure-Activity Relationship
Time Factors
Tritium
Blood Glucose metabolism
Erythrocytes metabolism
Sorbose blood
Subjects
Details
- Language :
- English
- ISSN :
- 0264-6021
- Volume :
- 131
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Biochemical journal
- Publication Type :
- Academic Journal
- Accession number :
- 4722437
- Full Text :
- https://doi.org/10.1042/bj1310211