A Stereospecific myo-Inositol/D-chiro-Inositol Transporter in HepG2 Liver Cells

D- chiro -Inositol is an epimer of myo -inositol that is found in certain mammalian glycosylphosphatidylinositol protein anchors and inositol phosphoglycans possessing insulin-like bioactivity. In order to generate a probe for metabolic studies, D- chiro -[3- 3 H]inositol was synthesized by selective reduction of D- chiro -3-inosose at pH 6.5 with sodium borotritide. D- chiro -[3- 3 H]Inositol was taken up by HepG2 human liver cells through a saturable and stereospecific pathway in which D- chiro -inositol and myo -inositol competed equally but L- chiro -inositol was not recognized. D-Glucose, but not L-glucose, competed for D- chiro -[3- 3 H]inositol uptake over glucose concentrations of 4-28 mM. Maximum transport capacity was 717 pmol/mg cell protein/3 h with a K value of 348 μM. Uptake was reduced by 76% when sodium was eliminated from the medium and by 94% when the experiment was performed at 0°C. The new myo /D- chiro -inositol transporter is distinct from the sodium- myo -inositol co-transporter found in many tissues and accounts for all of the saturable D- chiro -inositol uptake and for a portion of the saturable low affinity myo -inositol uptake in HepG2 cells. It may allow D- chiro -inositol to be used by cells in the presence of a relatively large amount of competing myo -inositol.