SN4
SHORT NOTE
5M
★ High-yield
Define zymogens. Give examples and explain their physiological importance.
Definition
Zymogens (proenzymes) = inactive precursors of enzymes, activated by irreversible proteolytic cleavage of one or more peptide bonds.
WHY the Body Uses Zymogens
- Protects the synthesising cell from being digested by its own enzyme
- Allows the enzyme to be stored safely and released in bulk when needed
- Permits activation at the correct site — the gut lumen, not the pancreas
- Gives a rapid, amplifying cascade, as in coagulation and complement
- Activation is irreversible, so control must be exerted by separate inhibitors
Important Examples
| Zymogen | Active enzyme | Activator | Site |
|---|---|---|---|
| Pepsinogen | Pepsin | HCl, then pepsin itself (autocatalysis) | Stomach |
| Trypsinogen | Trypsin | Enterokinase (enteropeptidase), then trypsin | Duodenum |
| Chymotrypsinogen | Chymotrypsin | Trypsin | Duodenum |
| Procarboxypeptidase | Carboxypeptidase | Trypsin | Duodenum |
| Proelastase | Elastase | Trypsin | Duodenum |
| Prothrombin | Thrombin | Prothrombin activator (Xa, Va, Ca2+) | Blood |
| Fibrinogen | Fibrin | Thrombin | Blood |
| Plasminogen | Plasmin | TPA, urokinase, streptokinase | Clot |
| Procollagenase | Collagenase | Proteases | Connective tissue |
CLINICAL PEARL
Trypsin is the master activator of the pancreatic zymogens — it activates chymotrypsinogen, procarboxypeptidase, proelastase and more trypsinogen. Block trypsin and the whole cascade fails.
Protective Mechanisms Against Premature Activation
- Pancreatic secretory trypsin inhibitor (SPINK1) within the acinar cell
- Zymogens stored in membrane-bound granules, separate from lysosomal enzymes
- Enterokinase is confined to the duodenal mucosa, not the pancreas
- The low intracellular calcium of the acinar cell disfavours activation
Applied Aspects
- Acute pancreatitis — the protective mechanisms fail and trypsinogen is activated within the pancreas → autodigestion. Commonest causes are gallstones and alcohol
- Hereditary pancreatitis — a mutation in trypsinogen (PRSS1) makes it resistant to inactivation, or a SPINK1 mutation removes the inhibitor
- α1-antitrypsin is the natural inhibitor of elastase; its deficiency causes panacinar emphysema and cirrhosis
- Thrombolytic therapy exploits the zymogen principle — streptokinase and tPA convert plasminogen to plasmin within the clot
All questions in Enzymes
- Q1Define enzymes. Classify them according to the IUBMB system and describe the mechanism of enzyme action. Add a note on enzyme specificity. ★
- Q2Describe the effect of substrate concentration on enzyme activity. Explain the Michaelis–Menten equation, the significance of Km and the Lineweaver–Burk plot. ★
- Q3Classify enzyme inhibition. Describe competitive, non-competitive and uncompetitive inhibition with their effects on Km and Vmax, and give examples. ★
- Q4Describe the mechanisms regulating enzyme activity. Explain allosteric regulation, covalent modification and enzyme induction with examples. ★
- Q5Describe the diagnostic importance of serum enzymes. Give the enzyme profile in myocardial infarction and liver disease. Add a note on isoenzymes. ★
- SN1Define coenzymes. Enumerate the coenzymes derived from vitamins with their functions. ★
- SN2Define isoenzymes. Describe the isoenzymes of lactate dehydrogenase and creatine kinase with their clinical significance. ★
- SN3Describe allosteric enzymes with their characteristics and examples. Add a note on feedback inhibition. ★
- SN4Define zymogens. Give examples and explain their physiological importance. ★
- SN5Define Km. Describe its significance with the example of hexokinase and glucokinase. ★
- SN6Describe competitive inhibition with its characteristics and medically important examples. ★
- SN7Describe the types of enzyme specificity with examples.