Enzymes as drug targets

3 Kinetics Single Substrate Multiple Substrates Metabolism of Drugs 

The catalytic action of enzymes arises from their underlying protein structure. Therefore, appreciation of enzymes first requires a working understanding of the different levels of protein structure. 

Enzymes are catalysts, and catalysts have two key qualities. First, catalysts increase the rate of a reaction. Second, catalysts are not consumed in the reaction and therefore do not appear in the overall balanced reaction equation. Catalysts appear throughout everyday life. Most simple hand tools are catalysts. For example, a shovel greatly accelerates the rate at which one can move dirt or gravel. Furthermore, the same shovel can be used day after day and work as efficiently on the last day as on the first. A shovel facilitates a process but is not consumed by the process. Moving dirt does not absolutely require a shovel, but using a shovel certainly beats using one s bare hands. 

Enzymes have all the qualities mentioned previously for an acid catalyst. Enzymes are not consumed in the overall reaction, and they accelerate both the forward and reverse reaction by altering the mechanism and/or lowering the activation energy of the key steps. Often, the product immediately reacts in a subsequent reaction, and the reverse reaction of the enzyme can be ignored. 

FIGURE 4.2 Acid catalyzed reaction coordinate for hydrolysis of 4.1 

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The attractiveness of enzymes as drug targets results not only from the essentiality of their catalytic activity but also from the fact that enzymes, by their very nature, are highly amenable to inhibition by small molecular weight, drug-like molecules. Because of this susceptibility to inhibition by small molecule drugs,... 

Another computational approach for identification of metabolic enzymes as drug targets involves the concept of minimal cut sets, which are defined as the minimal set of reaction in a network whose inactivation will definitively lead to a failure in a particular network function. Screening parasite metabolic networks for all possible minimal cut sets and identification of those which ate small (i.e., contain few enzymes) and not present in the host could serve to identify potential drug targets. 

Ueda N, Okamoto Y, Tsuboi K (2005) Endocannabinoid-related enzymes as drug targets with special reference to N-acylphosphatidylethanolamine-hydrolyzing phospholipase D. Curr Med Chem 2005(12) 1413-1422... 

D. Various ligands for a single target Enzymes as Drug Targets... 

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