A Model for The Mode of Action of Cytochalasin B Inhibition of D-Glucose Transport in the Human Erythrocyte

1975 ◽  
Vol 53 (10) ◽  
pp. 1078-1084 ◽  
Author(s):  
N. F. Taylor ◽  
G. L. Gagneja
Keyword(s):  
Glucose Transport ◽  
Human Erythrocyte ◽  
Mode Of Action ◽  
Cytochalasin B ◽  
Transport Model ◽  
Molecular Model ◽  
Competitive Inhibitor ◽  
Carrier Protein ◽  
Human Erythrocyte Membrane ◽  
Competitive Inhibitors

By an optical method, cytochalasin B is shown to be a competitive inhibitor of D-glucose transport across the human erythrocyte membrane with Ki of 1.2 × 10−7 M. A Drieding molecular model of cytochalasin B reveals an almost identical spatial distribution of four oxygen atoms to those found in the C1-conformation of β-D-glucopyranose and implicated in hydrogen bonding to the carrier protein associated with D-glucose transport. The stereochemistry of this transport model is discussed.On the basis of the interoxygen distances found in cytochalasin B, hydrocortisone, prednisolone, corticosterone, and phenolphthalein are considered as analogues and are shown to be competitive inhibitors of D-glucose transport with Ki values of 2.2 × 10−4 M, 3.0 × 10−4 M, 4.0 × 10−4 M, and 2.5 × 10−5 M, respectively. These results are considered to be consistent with the proposed mode of action of cytochalasin B and also provide further support for the model of D-glucose stereospecifically hydrogen-bonded to a carrier protein.

scholarly journals Glycation of the human erythrocyte glucose transporter in vitro and its functional consequences

1990 ◽  
Vol 268 (3) ◽  
pp. 661-667 ◽  
Author(s):  
P J Bilan ◽  
A Klip
Keyword(s):  
Erythrocyte Membrane ◽  
Human Erythrocyte ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Competitive Inhibitor ◽  
Human Erythrocyte Membrane ◽  
Functional Consequences ◽  
High Concentrations ◽  
Erythrocyte Membrane Proteins

Glycation of human erythrocyte membrane proteins was induced by incubation in vitro with high concentrations (80 mM or 200 mM) of D-glucose for 3 or 6 days. The extent of glycation was quantified from the covalent incorporation of 3H by reduction of the glucose glycation products with NaB3H4. For membranes incubated for 3 days with 80 mM-D-glucose, glycation in vitro of Band 4.5 (containing the glucose transporter) was equivalent to 0.11 mol of glucose/mol of glucose transporter, compared with 3H labelling in 3-day-incubated control membranes of 0.055 mol of glucose/mol of glucose transporter. In membranes incubated for 6 days with 200 mM-D-glucose, glycation increased to 0.21 mol of glucose/mol of glucose transporter, whereas the controls without glucose had 0.11 mol of glucose/mol of glucose transporter. Glycation in vitro was accompanied by a fall in the Bmax of binding of [3H]cytochalasin B (a competitive inhibitor of glucose transport), without any change in the binding affinity. The data suggest that glycated glucose transporters have decreased ability to bind cytochalasin B. It is proposed that glycation can alter glucose transporter activity.

Purine derivatives as competitive inhibitors of human erythrocyte membrane phosphatidylinositol 4-kinase

1990 ◽  
Vol 33 (8) ◽  
pp. 2073-2080 ◽  
Author(s):  
Rodney C. Young ◽  
Martin Jones ◽  
Kevin J. Milliner ◽  
Kishore K. Rana ◽  
John G. Ward
Keyword(s):  
Erythrocyte Membrane ◽  
Human Erythrocyte ◽  
Purine Derivatives ◽  
Human Erythrocyte Membrane ◽  
Competitive Inhibitors ◽  
Phosphatidylinositol 4

FUNCTIONAL AND MOLECULAR CHARACTERISTICS OF A PRIMITIVE VERTEBRATE GLUCOSE TRANSPORTER: STUDIES OF GLUCOSE TRANSPORT BY ERYTHROCYTES FROM THE PACIFIC HAGFISH (EPTATRETUS STOUTI)

1994 ◽  
Vol 186 (1) ◽  
pp. 23-41 ◽  
Author(s):  
J. D. Young ◽  
Y. Syn ◽  
C. M. Tse ◽  
A. Davies ◽  
S. A. Baldwin
Keyword(s):  
Glucose Transport ◽  
Human Erythrocyte ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Sequence Similarity ◽  
Erythrocyte Membranes ◽  
Molecular Characteristics ◽  
Relative Molecular Mass ◽  
Amino Acid Sequence Homology ◽  
The Pacific

The characteristics of glucose transport were investigated in erythrocytes of a primitive vertebrate, the Pacific hagfish (Eptatretus stouti) Lockington. Transport of glucose by intact hagfish erythrocytes and by phospholipid vesicles reconstituted with n-octylglucoside extract of hagfish erythrocyte membranes was rapid and mediated by a saturable stereospecific mechanism sensitive to inhibition by cytochalasin B. Covalent photoaffinity labelling experiments with [3H]cytochalasin B identified the hagfish glucose transporter on SDS/polyacrylamide gels as a protein with an apparent average Mr of 55 000. Amino acid sequence homology between the hagfish and human erythrocyte glucose transporters (GLUT 1) was investigated in immunoblotting experiments using a panel of 12 different antipeptide antisera and affinity-purified antibodies raised against cytoplasmic extramembranous regions of the human transporter, and with an antibody to the intact purified human protein. The latter antibody labelled a component in the membrane with the same apparent Mr as cytochalasin B. Two affinity-purified antipeptide antibodies, corresponding to residues 240–255 and 450–467 of the human erythrocyte transporter, also labelled a component in the membrane with this relative molecular mass, demonstrating localised sequence similarity between the polypeptides of the two species within the central cytoplasmic loop and within the cytoplasmic C-terminal region. Glucose transport by hagfish erythrocytes was not coupled to the movement of protons.

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