Enzyme inhibitor, occurrence

Enzyme inhibitors of a protein nature are of significant concern because of widespread occurrence. The most common of these affect the pancreatic enzymes, trypsin and chymotrypsin. and arc found in legumes, as well as in egg whites and potatoes. 

HIV protease inhibitors are transition-state analogs (Chapter 9, Section 9.2.6) HIV protease binds them much more tightly than the natural substrate because the substrate must be distorted to assume its transition-state configuration. Thus, HIV protease inhibitors are competitive enzyme inhibitors and thereby prevent the maturation and infectivity of the viral particle. They offer advantages over RTIs with respect to efficacy, safety, and occurrence of resistance. However, just like RTIs, HIV protease inhibitors are most often offered in combination with therapies based on another mode of action. Structures and data for the five approved HIV protease inhibitors are shown in Figure 13.14 and in Table 13.5. 

The occurrence of active transport does not, of course, involve a violation of the second law of thermodynamics. Metabolic processes are occurring at the same time these reactions are spontaneous and thus exergonic, and are coupled with the transport process. Certain enzyme inhibitors, such as CN ions and other agents which inhibit ATP formation will cause these chemical processes to cease then active transport no longer occurs. 

Since this enzyme was first isolated and purified from swine lung [106], a number of papers have been published reporting its occurrence in animal tissues, substrate specificity, enzyme inhibitors, reaction mechanism and physiological function. These papers have been anteceded by two comprehensive review articles [107,108]. 

The ubiquitous occurrence of proteinases is accompanied by a similar distribution of fairly specific proteins that inhibit these enzymes. In normal health, there is a delicate balance between the levels of enzymes and their macromolecular inhibitors. This balance is particularly important in the blood-clotting clot-lysis scheme. Since the total volume of blood in the adult human body is only about 5 1, a massive response is required in the event of an injury that results in a rapid haemorrhage. Some positive feedback is present in the blood-clotting mechanism in order to achieve this rapid response, but clearly this must be sensitively controlled by endogenous inhibitors if a thrombosis is not to occur. 

Table III. Effect of a lipoxygenase-specific inhibitor on the occurrence of enzymically- and oxidatively-derived volatiles in fish.

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