Uptake of glutamate, not glutamine synthetase, regulates adaptation of mammalian cells to glutamine-free medium.

Two cell lines (McCoy and MDCK) were studied in an attempt to understand the metabolic changes associated with adaptation to glutamine-free medium (GMEM + gmate). McCoy cells assumed normal growth rates after 2-3 passages in this medium whereas MDCK cells showed no growth in GMEM + gmate. The glutamine synthetase (GS) activity of both cell lines was elevated (up to x 9) as glutamine was depleted from normal media (GMEM + gmine). The high activity of GS was maintained during McCoy cell growth in GMEM + gmate. However, there was no apparent significant difference between the two cell lines in the pattern of changes of GS activity in response to glutamine. The cellular uptake rates of glutamine and glutamate from the medium differed significantly between the two cell lines. During the adaptation of McCoy cells to GMEM + gmate, the rate of glutamate uptake doubled to a value of 0.54 nmol/min per mg cell protein whereas the maximum value for MDCK cells was considerably lower (0.04 nmol/min per mg cell protein). We propose that the difference in intrinsic ability for glutamate transport accounts for the difference in growth response between the two cell lines in the glutamine-free medium.