The optimum pH for most mammalian cell cultures is approximately:
Mammalian cells operate optimally near physiological pH 7.4 because intracellular enzyme active sites evolved to function at cytosolic pH 7.2 to 7.4 where ionization states of catalytic residues critical for activity maintain balance. Histidine imidazole side chain pKa around 6.0 partially protonated at neutral pH acts as proton donor acceptor in charge relay systems of serine proteases, carbonic anhydrase, and ATP synthase beta subunit. Deviation alters Michaelis constant Km and Vmax drastically, reducing efficiency. Extracellular pH is regulated via bicarbonate carbon dioxide buffering syste
Ref: Freshney Animal Cell Culture pH 7.4 optimum bistability; Alberts MBoC Henderson-Hasselbalch bicarbonate histidine catalytic ionization.