Proteinase Inhibitors and Their Clinical Significance

In the body, enzymes are compartmentalized and function under highly restricted conditions. Some enzymes (e.g., proteinases) are not substrate-specific. When present in active form in an inappropriate part of the body, they act indiscriminately and cause considerable damage to the tissue. Inhibitors inactivate these enzymes at sites where their action is not desired. Proteinase inhibitors, which are themselves proteins, are widely distributed in intracellular and extracellular fluids. Protein inhibitors of enzymes other than proteinases are relatively rare. Such inhibitors are available for a-amylases, deoxyribonuclease I, phospholipase A, and protein kinases. 

Principal Proteinase Inhibitors in Human Blood Plasma  

Name Concentration (mg/100 mL) Mol. Wt. Number of Polypeptide Chains Heads  

Proteinases and their inhibitors play a major role in metastasis of cancer. Metastasis of tumors requires remodeling of extracellular matrix (ECM). Remodeling is a balance between proteolysis and respective proteinase inhibitors. This process is aided by proteolytic enzymes 

CHAPTER 6 Enzymes I General Properties, Kinetics, and Inhibition 

---