2.11:
pH Regulation in Cells
pH is a measure of H+ concentration in a solution and indicates its level of acidity or alkalinity.
The pH scale ranges from 0 to 14, where seven is considered neutral, a value below seven is acidic, and a value above seven is basic.
The typical cytoplasmic pH lies in a slightly alkaline range of 7.0 to 7.4. Large variations in this intracellular pH can affect critical cellular processes, such as metabolism, membrane potential, and signaling pathways.
For instance, CO2 – the end product of cellular respiration, combines with H2O to form H2CO3 .
H2CO3 is a weak acid that readily dissociates, slowly acidifying the cytoplasm and leading to cellular stress.
Therefore, cells regulate their internal pH using ion exchangers to alter the hydrogen ion concentration.
The Na+/H+ exchanger helps to balance the intracellular pH by coupling the efflux of H+ with the influx of Na+.
Similarly, Cl−-HCO3− exchangers play an important role in maintaining intracellular pH by effluxing HCO3− ions in exchange for Cl− ions.
2.11:
pH Regulation in Cells
pH plays a critical role in maintaining normal cellular activities. It helps maintain the structure and function of various proteins, dictates the charge on cellular membranes, and is crucial for metabolic reactions inside the cell. Moreover, cells use the energy from the proton motive force to generate ATP.
Cytosolic pH
Under physiological conditions, the cytosolic pH is slightly more acidic than the extracellular pH. However, cells must prevent further acidification of their cytosol to maintain their membrane potential and carry out normal functioning. Therefore, they employ several specialized proton-translocating machinery—antiporters, symporters, and proton-pumping ATPases—to tightly regulate the steady-state pH.
Cellular Organelles and pH Homeostasis
The compartmentalization inside the eukaryotic cells helps to provide distinct environmental conditions to carry out specific functions within different membrane-enclosed organelles. The internal pH in these different compartments is highly variable, but it is an important determinant of their effective functioning.
For example, cytochromes located on the inner mitochondrial membrane efflux protons using energy from electron flow. This helps to establish a proton gradient across the mitochondrial membrane that is used to generate chemical energy in the form of ATP. Similarly, lysosomes maintain an internal acidic pH by pumping protons from the cytosol using energy from ATP hydrolysis. This is essential for the functioning of the lysosomal enzymes.
However, some organelles, including the nucleus, endoplasmic reticulum, and peroxisomes, need to maintain their internal pH in equilibrium with the cytoplasm. Therefore, they lack intrinsic pH-regulatory systems and are highly permeable to protons.
Dysregulation of Intracellular pH
Certain metabolic or genetic conditions may disrupt the steady-state pH of the cytoplasm or the organelles inside the cell and lead to disease. For example, mutations in chloride carriers, such as CLCN6 and CLCN7, present on late endosomes and lysosomes have been linked to osteoporosis and lysosomal storage disease. Similarly, mutations in the CLCN5 channel hinder luminal acidification and production of early endosomes in renal epithelial cells and can eventually lead to kidney failure.