What is in-situ activation of chymotrypsinogen? Explain how the correct folding of the enzyme chymotrypsin leads to its function as proteolytic enzyme
Answers
Explanation:
We turn now to a different mechanism of enzyme regulation. Many enzymes acquire full enzymatic activity as they spontaneously fold into their characteristic three-dimensional forms. In contrast, other enzymes are synthesized as inactive precursors that are subsequently activated by cleavage of one or a few specific peptide bonds. The inactive precursor is called a zymogen (or a proenzyme). A energy source (ATP) is not needed for cleavage. Therefore, in contrast with reversible regulation by phosphorylation, even proteins located outside cells can be activated by this means. Another noteworthy difference is that proteolytic activation, in contrast with allosteric control and reversible covalent modification, occurs just once in the life of an enzyme molecule.
Specific proteolysis is a common means of activating enzymes and other proteins in biological systems. For example:
1.
The digestive enzymes that hydrolyze proteins are synthesized as zymogens in the stomach and pancreas (Table 10.3).
2.
Blood clotting is mediated by a cascade of proteolytic activations that ensures a rapid and amplified response to trauma.
3.
Some protein hormones are synthesized as inactive precursors. For example, insulin is derived from proinsulin by proteolytic removal of a peptide.
4.
The fibrous protein collagen, the major constituent of skin and bone, is derived from procollagen, a soluble precursor.
5.
Many developmental processes are controlled by the activation of zymogens. For example, in the metamorphosis of a tadpole into a frog, large amounts of collagen are resorbed from the tail in the course of a few days. Likewise, much collagen is broken down in a mammalian uterus after delivery. The conversion of procollagenase into collagenase, the active protease, is precisely timed in these remodeling processes.
6.
Programmed cell death, or apoptosis, is mediated by proteolytic enzymes called caspases, which are synthesized in precursor form as procaspases. When activated by various signals, caspases function to cause cell death in most organisms, ranging from C. elegans (Section 2.4.3) to human beings. Apoptosis provides a means sculpting the shapes of body parts in the course of development and a means of eliminating cells producing anti-self antibodies or infected with pathogens as well as cells containing large amounts of damaged DNA.
Table 10.3. Gastric and pancreatic zymogens.
Table 10.3
Gastric and pancreatic zymogens.
We next examine the activation and control of zymogens, using as examples several digestive enzymes as well as blood-clot formation.
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10.5.1. Chymotrypsinogen Is Activated by Specific Cleavage of a Single Peptide Bond
Chymotrypsin is a digestive enzyme that hydrolyzes proteins in the small intestine. Its mechanism of action was discussed in detail in Chapter 9. Its inactive precursor, chymotrypsinogen, is synthesized in the pancreas, as are several other zymogens and digestive enzymes. Indeed, the pancreas is one of the most active organs in synthesizing and secreting proteins. The enzymes and zymogens are synthesized in the acinar cells of the pancreas and stored inside membrane-bounded granules (Figure 10.31). The zymogen granules accumulate at the apex of the acinar cell; when the cell is stimulated by a hormonal signal or a nerve impulse, the contents of the granules are released into a duct leading into the duodenum.
Figure 10.31. Secretion of Zymogens by an Acinar Cell of the Pancreas.
Figure 10.31
Secretion of Zymogens by an Acinar Cell of the Pancreas.
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