Effect of oxygen limitation — when dissolved oxygen (DO) drops below the critical level in mammalian culture, which metabolic changes drive the decline in viable cell density?

Introduction / Context:
Oxygen transfer is a key constraint in high-density animal cell culture. When DO falls below a critical value, cells rewire metabolism, often decreasing productivity and viability. Understanding the linked glutamine and glucose pathways helps troubleshoot bioreactor performance.

Given Data / Assumptions:

• Critical DO is the threshold below which oxygen becomes limiting for aerobic metabolism.
• Glutamine and glucose are primary fuels; their catabolism affects by-products (ammonia, lactate).
• Observed outcome: decline in viable cell concentration.

Concept / Approach:

With insufficient oxygen, cells reduce oxidative metabolism, increasing glycolytic flux and lactate formation from glucose. In parallel, glutamine is incompletely oxidized, contributing to by-product accumulation and pH/ammonia stress. Together, these metabolic shifts burden cells, decrease growth, and promote apoptosis/necrosis.

Step-by-Step Solution:

Verification / Alternative check:

Bioprocess data typically show negative correlations between prolonged low DO and viability, accompanied by elevated lactate and ammonia, especially at high cell densities.

Why Other Options Are Wrong:

Ammonia accumulation is largely coupled to glutamine metabolism (so “only, unrelated” is incorrect); ROS usually decrease when O2 is low, not rise from “excessive oxidative phosphorylation.”

Common Pitfalls:

Blaming a single metabolite only; ignoring that oxygen limitation simultaneously impacts multiple pathways.

Final Answer:

Both (a) and (b)