Hexose transport derepressed and refractory to purine regulation in NAD(H)-Depleted Nil cells

Abstract

Nil hamster fibroblasts depleted of NAD(H) by growth in medium devoid of nicotinamide (NAm-MEM) exhibit up to 2-3-fold higher rates of glucose transport. Derepression of glucose transport is observed only when Nil cells have become severely depleted of both intracellular NAD(H) and ATP, despite the continued presence of 5.5 mM D-glucose in the growth medium. Neither the initial rate of transport, approximated from 3-O-methylglucose uptake, nor accumulation of D-glucose itself is repressed upon restoring nicotinamide to the medium. Exposure of the cells to NAD+ (10(-5) M), however, leads to a sharp curtailment of transport within 2 to 3 hours. The purines, hypoxanthine and guanine, that sharply reduce glucose transport capacity of normal cells, have no significant effect upon transport activity of NAD(H)-depleted cells.