Figure 4. Non-canonical anaplerotic glutamine metabolism is enhanced in chronic acidosis.
(A) LC-MS/MS-based metabolomic analysis of non-canonical glutamine metabolism in control (7.4) and low pH (7.0) culture conditions. (B) Quantitative real-time PCR analysis of genes coding for enzymes involved in non-canonical glutamine metabolism in cells cultured under control and low pH. (C–D) Sensitivity of S2-013 and Capan-1 cells to treatment with aminooxyacetic acid (AOA; C) and to epicogallocatechin gallate (EGCG; D) in control and low pH conditions. (E) A schematic illustration of potential metabolite flow under low pH. Bold arrows indicate glutamine metabolism in low pH through the non-canonical pathway. Data in bar charts is normalized to the values for the control pH (7.4). Error bars represent mean ± S.E.M. from at least three different replicates. A two-tailed Student’s t-test was conducted to compare control versus low pH in Figure 4A and 4B with p-values * p<0.05, **p<0.01, ***p<0.001.
