Figure 3.

The α-ketoglutarate/citrate ratio determines reductive glutamine utilization. (a) Acetate is a third carbon source beside glucose and glutamine that fuels the citrate pool. (b) α-ketoglutarate/citrate ratio, and (c) reductive glutamine contribution to citrate normalized to the total glutamine contribution to citrate, with and without acetate supplementation in the control condition and in the presence of metformin. (d) Ratio of oxidative versus reductive glutamine utilization in the presence of metformin with and without acetate measured with a U¹³C-glutamine tracer. (e) Glutamine contribution to palmitate in metformin treatment conditions with and without acetate supplementation. (f) Ratio of oxidative versus reductive glutamine utilization in the presence of metformin with and without different concentrations of citrate measured with a U¹³C-glutamine tracer determined from fumarate, malate and asparate. All error bars indicate the standard deviation. p-values are < 0.05. All p-values (students T-test, two tailed, unequal variance) and error bars are calculated from two independent replicates.