A metabolic core model elucidates how enhanced utilization of glucose and glutamine, with enhanced glutamine-dependent lactate production, promotes cancer cell growth: The WarburQ effect
Fig 4
ENGRO1 biomass optimization for different boundary conditions.
A) ENGRO1 maximal growth rate (z-axis and coloring) as a function of glucose (G) and oxygen availability when glutamine availability is constant (Q:1). The arrows represent example mutational paths in the fitness landscape. The insets represent 2D-slices of the 3D mesh when oxygen availability takes value 6. B) The growth rate (over G) and lactate secretion (over G) as a function of glutamine availability (indicated as the glutamine over glucose ratio QGR), when the O2GR takes value 3 (O2:6 (mM h-1), G:3 (mM h-1)). C) Lactate efflux (z-axis) and PDH flux (color scale) scaled on glucose uptake as a function of QGR and O2GR. Red points highlight the O2GR level for which maximum lactate secretion is observed. Left inset: level of oxygen to be considered critical as a function of QGR. Critical oxygen is computed both as the point in which lactate secretion is at the maximum (blue dots) and the point in which PDH reaches its minimum (red dots). Right inset: pyruvate dehydrogenase flux as a function of glutamine availability (QGR) for different oxygen availability values (the O2GR value is reported on top of the corresponding curve).