In mammalian cell culture, what is the principal effect of lactate accumulation on the culture environment and cell health?

Introduction / Context:
Cells metabolize glucose through glycolysis and, when flux is high or oxygen is limiting, produce lactate. In closed systems, lactate accumulation acidifies the medium and can impair growth and productivity, a central concern in bioprocess optimization.

Given Data / Assumptions:

• Lactate is an acidic metabolite.
• Accumulation occurs under high glycolytic rates or suboptimal aeration.
• We consider standard bicarbonate-buffered media.

Concept / Approach:
Lactate carries protons into the medium. As its concentration rises, buffering capacity is exceeded and pH falls. Lower pH stresses cells, alters enzyme activities, affects membrane transport, and can trigger apoptosis or growth arrest.

Step-by-Step Solution:

Verification / Alternative check:
Industrial fed-batch processes control glucose feed and base addition to limit lactate formation and maintain pH, confirming its negative impact.

Why Other Options Are Wrong:

Common Pitfalls:
Assuming pH control alone eliminates lactate toxicity; even at corrected pH, high lactate can still inhibit growth.

Final Answer:
Reduction of pH leading to loss of cell viability over time.