Bioprocess by-products: What is the effect of excess lactate and ammonium accumulation on mammalian cells grown in vitro?

Introduction / Context:
Lactate (from glycolysis) and ammonium (from glutamine deamidation) are common inhibitory by-products in mammalian bioprocessing. Their control is crucial for stable cultures and high product yields.

Given Data / Assumptions:

• Both metabolites can accumulate during high-density culture.
• We consider typical pH and osmolality ranges used in industry.
• Cells are sensitive to metabolic waste buildup.

Concept / Approach:
Lactate lowers pH and perturbs energy metabolism; ammonium alters intracellular pH regulation, impairs glycosylation, and inhibits key enzymatic steps. Together they decrease specific growth rate and recombinant protein productivity.

Step-by-Step Solution:

Verification / Alternative check:
Optimization strategies (controlled feeding, glutamine substitutes, pH control, perfusion) specifically target lowering lactate and ammonium, confirming their inhibitory nature.

Why Other Options Are Wrong:

Common Pitfalls:
Assuming that pH correction eliminates all inhibition; intracellular effects persist even at corrected bulk pH.

Final Answer:
They act as growth inhibitors that reduce proliferation and productivity.