Bioprocessing effect of carbon dioxide: Excess CO2 can suppress cell growth and productivity primarily by which mechanism(s)?

Introduction / Context:
In mammalian and microbial cell culture, dissolved CO2 is a critical process parameter. Elevated CO2 partial pressure impacts cellular physiology and product quality, making its control essential in bioreactors and large-scale bioprocesses.

Given Data / Assumptions:

• CO2 is membrane-permeable and hydrates to carbonic acid inside cells.
• Intracellular pH and carbamylation reactions can modulate enzyme function and metabolism.
• High CO2 may also depress respiration and energy metabolism.

Concept / Approach:
CO2 enters cells, forming carbonic acid and bicarbonate, lowering intracellular pH and altering acid–base balance. Carbamate formation on proteins can change activity. In parallel, respiratory enzymes and mitochondrial function can be downregulated by hypercapnic conditions. While medium pH shifts occur, well-buffered media can mask external pH changes even when intracellular perturbation remains significant.

Step-by-Step Solution:

Verification / Alternative check:
Process literature shows correlations between high pCO2 and reduced growth/productivity, reversible by CO2 stripping or base addition with careful control of intracellular pH indicators.

Why Other Options Are Wrong:

• Only respiration or only medium pH does not capture the full effect.
• CO2 does not drive dissolved oxygen to zero; O2 solubility is governed mainly by its own partial pressure and temperature.

Common Pitfalls:
Assuming controlling bulk pH alone eliminates CO2 stress; overlooking intracellular acidification despite extracellular pH control.

Final Answer:
Both inhibiting respiration and altering intracellular pH