FIGURE 3-29 The pH dependence of enzyme activity. In some cases, ionizable (pH-titratable) groups in enzyme active sites or elsewhere in enzymes must be either protonated or deprotonated to permit proper substrate binding or catalysis, or to permit the enzyme to adopt the correct conformation. Measurement of enzyme activity as a function of pH can be used to identify the pK_a’s of these groups. The pancreatic serine proteases, such as chymotrypsin, exhibit maximum activity at around pH 8 because of titration of the active-site His-57 (required for catalysis, pK_a ~6.8) and of the amino terminus of the protein (required for proper conformation, pK_a ~9). Many lysosomal hydrolases have evolved to exhibit a lower pH optimum (~4.5) to match the low internal pH in the lysosomes in which they function.

[Data from P. Lozano, T. De Diego, and J. L. Iborra, 1997, Eur. J. Biochem. 248:80–85, and W. A. Judice et al., 2004, Eur. J. Biochem. 271:1046–1053.]