Buffering against pH Changes in Biological Systems

Almost every biological process is pH dependent; a small change in pH produces a large change in the rate of the process. This is true not only for the many reactions in which the H⁺ ion is a direct participant, but also for those in which there is no apparent role for H⁺ ions. The enzymes that catalyze cellular reactions, and many of the molecules on which they act, contain ionizable groups with characteristic pKa values. The protonated amino and carboxyl groups of amino acids and the phosphate groups of nucleotides, for example, function as weak acids; their ionic state depends on the pH of the surrounding medium. As we noted above, ionic interactions are among the forces that stabilize a protein molecule and allow an enzyme to recognize and bind its substrate. Cells and organisms maintain a specific and constant cytosolic pH, keeping biomolecules in their optimal ionic state, usually near pH 7. In multicellular organisms, the pH of extracellular fluids is also tightly regulated. Constancy of pH is achieved primarily by biological buffers: mixtures of weak acids and their conjugate bases. We describe here the ionization equilibria that account for buffering, and we show the quantitative relationship between the pH of a buffered solution and the pKa of the buffer. Biological buffering is illustrated by the phosphate and carbonate buffering systems of humans.