Alterations in red blood cell sugar transport by nanomolar concentrations of alkyl lysophospholipid.
Acyl lysolipids presented in vitro to red blood cells in amounts comparable to blood serum levels inhibit protein-mediated glucose transport (Naderi, A., Carruthers, A. and Melchior, D.L. (1989) Biochim. Biophys. Acta 985, 173-181). In this study, an alkyl lysolipid (2-O-methyl-1-O-octadecyl-sn-glycero-3- phosphocholine; ALP), was found to be an order of magnitude more effective in inhibiting sugar transport than the most potent acyl lysolipid. Bilayer concentrations of ALP as low as 5 ALP molecules per transporter (0.1 mol% of total membrane lipid) result in a 50% inhibition of transport activity. ALP acts as a competitive inhibitor of exchange L-glucose transport, of CCB binding to the glucose transporter and of D-glucose inhibition of CCB binding to the transporter. Inhibition of zero-trans sugar uptake by ALP is noncompetitive. The two enantiomers of ALP show a different ability to inhibit sugar transport. The action of ALP is consistent with a mechanism in which ALP interacts with a transmembrane portion of the sugar transport molecule resulting in a competitive displacement of D-glucose or cytochalasin B from the cytosolic facing side of the transport molecule. The simplest explanation of our findings is a direct interaction of the ALP molecule with the transport protein.
Department of Biochemistry, University of Massachusetts Medical School, Worcester 01655.
D L
DL
Melchior
A
A
Carruthers
A
A
Makriyannis
R I
RI
Duclos
O H
OH
Abdel-Mageed
D001667:Binding, Competitive; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008051:Lipid Bilayers / Q000378:metabolism*; D008246:Lysophospholipids / Q000138:chemical synthesis / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009994:Osmolar Concentration
D001786:Blood Glucose; D008051:Lipid Bilayers; D008246:Lysophospholipids; D009004:Monosaccharide Transport Proteins; D003571:Cytochalasin B