Practice question

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 system mirroring blood, calculated by Henderson-Hasselbalch equation pH equals 6.1 plus log ratio of bicarbonate concentration to dissolved CO2. With sodium bicarbonate 3.7 grams per liter and 5 to 10 percent CO2 headspace at 37 degrees Celsius, pH stabilizes near 7.4. Mammalian cells export protons via NHE1 Na+/H+ exchanger isoform one electroneutral driven by sodium gradient maintained by Na+/K+ ATPase consuming ATP, and via H+ vacuolar ATPase in acidic organelles. Alkaline pH deviation above 7.