Enzyme Activation

There are a number of important cases in which enzymes are produced as inactive forms. In the cells of the pancreas, for example, many digestive enzymes are produced as inactive zymo-gens, which are activated after they are secreted into the intestine. Activation of zymogens in the intestinal lumen (cavity) protects the pancreatic cells from self-digestion.

In liver cells, as another example, the enzyme that catalyzes the hydrolysis of stored glycogen is inactive when it is produced, and must later be activated by the addition of a phosphate group. A different enzyme, called a protein kinase, catalyzes the addition of the phosphate group to that enzyme. At a later time, enzyme inactivation is achieved by another enzyme that catalyzes the removal of the phosphate group. The activation/inactivation of this enzyme (and many others) is thus achieved by the processes of phosphorylation/dephosphorylation.

Chapter Four

Substrates

Enzyme

-Cofactor

■ Figure 4.5 The roles of cofactors in enzyme function. In (a) the cofactor changes the conformation of the active site, allowing for a better fit between the enzyme and its substrates. In (b) the cofactor participates in the temporary bonding between the active site and the substrates,

Going back a step, the protein kinase itself may be produced as an inactive enzyme. In this case, activation of the protein kinase requires that it bind to a particular ligand (smaller molecule). Such ligands serve as intracellular regulators that are called second messengers. In many cases, this ligand is a molecule called cyclic AMP (cAMP). Cyclic AMP activates the protein kinase by promoting the dissociation of an inhibitory subunit from the active enzyme. Since the production of cyclic AMP within cells is stimulated by regulatory molecules that include neurotransmitters (see chapter 7, fig. 7.28) and hormones (see chapter 11, fig. 11.8), this topic will be discussed more completely in the context of neural and endocrine regulation.

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Essentials of Human Physiology

Essentials of Human Physiology

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