Drug-enzyme complex

Usually fairly high concentrations of such a drug are needed for effective control of an infection because the inhibitor (the false substrate) should occupy as many active centers as possible, and also because the natural substrate will probably have a greater affinity for the enzyme. Thus the equilibrium must be influenced and, by using a high concentration of the false substrate, the false substrate-enzyme complex can be made to predominate. The bacteria, deprived of a normal metabolic process, cannot grow and multiply. Now the body s defense mechanisms can take over and destroy them. 

The folate antagonists, pyrimethamine and sulfadiazine, inhibit the parasite s DHFR/TS synthase enzyme complex and the DHPS, respectively (Fig. 4) (see antimalarial drugs). To avoid deficiency of folic acid in patients treated with antifolate antagonists, folinic acid supplementation is recommended to reduce bone-marrow suppression. 

Fig. 5.4. Inactivation of /3-lactamases by cephalosporins (Fig. 5.1, Pathway b). The mechanism of this inactivation is similar to that of class-II inhibitors (Fig. 5.3, Pathway b) and is based on the slow hydrolysis of the acyl-enzyme complex (Pathway b). The normal deacylation of the acyl-enzyme complex represented by Pathway a results in the lost of antibacterial activity of the drug. The ratio between Pathways a and b is determined by the nature of the...

Type 3, immune complex vasculitis (serum sickness, Arthus reaction). Drug-antibody complexes precipitate on vascular walls, complement is activated, and an inflammatory reaction is triggered. Attracted neutrophils, in a futile attempt to phagocytose the complexes, liberate lysosomal enzymes that damage the vascular walls (inflammation, vasculitis). Symptoms may include fever, exanthema swelling of lymph nodes, arthritis, nephritis, and neuropathy. 

Aminoglutethimide (Cytadren) is a competitive inhibitor of desmolase, the enzyme that catalyzes the conversion of cholesterol to pregnenolone it also inhibits 11-hydroxylase activity. This drug also reduces estrogen production by inhibiting the aromatase enzyme complex in peripheral (skin, muscle, fat) and steroid target tissues. 

A LOOK AT COMPLEXITY AND EMERGENCE IN DRUG—ENZYME AND DRUG-RECEPTOR SYSTEMS... 

The potent oxidizing properties of this activated oxygen permit oxidation of a large number of substrates. Substrate specificity is very low for this enzyme complex. High solubility in lipids is the only common structural feature of the wide variety of structurally unrelated drugs and chemicals that serve as substrates in this system (Table 4-1). 

Suicide inhibitors, alternatively known as Kcat or irreversible mechanism based inhibitors (IMBIs), are irreversible inhibitors that are often analogues of the normal substrate of the enzyme. The inhibitor binds to the active site, where it is modified by the enzyme to produce a reactive group, which reacts irreversibly to form a stable inhibitor-enzyme complex. This subsequent reaction may or may not involve functional groups at the active site. This means that suicide inhibitors are likely to be specific in their action, since they can only be activated by a particular enzyme. This specificity means that drugs designed as suicide inhibitors could exhibit a lower degree of toxicity. 

Polyelectrolyte complexes can be prepared in a desired range of mass, size and structure density. The behavior of the PECs can be controlled by external parameters such as the ionic strength, the pH of the medium or the temperature. Therefore, such complexes should be of great interest as potential carrier systems for drugs, enzymes, or DNA because charged species can easily be integrated into the complex particles. 

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