Pathway selection: at very low glucose concentrations (below ~0.25 mmol/L), large portions of glucose and glutamine carbon are preferentially shunted through which route in mammalian cells?

Introduction / Context:
Carbon flux in mammalian cells depends on nutrient availability. When glucose becomes scarce, cells often reduce overflow glycolysis and rely more on oxidative metabolism, with glutamine contributing significantly to the TCA cycle anaplerosis.

Given Data / Assumptions:

• Glucose below ~0.25 mmol/L is limiting.
• Glutamine can supply carbon to the TCA via glutaminolysis.
• Oxygen is available (typical culture aeration).

Concept / Approach:
Under low-glucose conditions, cells increase reliance on oxidative phosphorylation to maximize ATP per substrate molecule, reducing lactate overflow. Glutamine carbon enters as alpha-ketoglutarate, supporting energy and biosynthesis in the TCA cycle.

Step-by-Step Solution:

Verification / Alternative check:
Metabolite profiling shows lower lactate accumulation at low glucose and higher oxygen consumption per unit carbon.

Why Other Options Are Wrong:

• B: Anaerobic dominance is typical with abundant glucose, not scarcity.
• C: Not equal; limitation favors oxidative use.
• D/E: Metabolism continues; PPP may contribute but is not exclusive.

Common Pitfalls:
Assuming the Warburg effect persists identically under nutrient limitation; cells adapt to maximize ATP yield.

Final Answer:
Oxidative pathway (TCA cycle and respiration)