• Nonesuch School

• CHEMISTRY 2025

T he theme of Chapter 10 is the regulation of protein function. Four major types of regulatory mechanisms are discussed in detail: allosteric control, isozymes, reversible covalent modification, and proteolytic activation. The authors use specific examples to illustrate the general structure-function relationships involved in these control mechanisms. To illuminate allosteric control, the authors discuss E. coli aspartate transcarbamoylase (ATCase), one of the best understood allosterically regulated proteins. ATCase is the enzyme that catalyzes the condensation of carbamoyl phosphate and aspartate in the first step of pyrimidine biosynthesis. Its activity is regulated both positively and negatively and provides a classic example of feedback inhibition of enzymes in multistep biosynthetic pathways. After the section on allosteric control, the authors illustrate the use of isozymes to regulate enzymes in a developmental and/or tissue-specific manner using lactate dehydrogenase as an example. Next the authors discuss the regulation of enzymes by covalent modifications such as phosphorylation, acetylation, lipidation, and ubiquination. The authors focus on reversible phosphorylation as a control mechanism and use cAMP-dependent protein kinase (PKA) as an example of how phosphorylation of target proteins can be regulated. The authors then turn to the activation of enzymes by proteolytic cleavage. They describe the proteolytic steps and conformational rearrangements that produce the active forms of chymotrypsin and trypsin from their inactive zymogens. The mechanisms of action of these enzymes were presented in Chapter 9. The authors conclude Chapter 10 with a discussion of the blood clotting cascade—the series of proteolytic activations of clotting factors that lead to the formation of fibrin clots. Several specific stimulatory and inhibitory proteins are described in connection with the proteolytic enzymes of the blood clotting cascade.