Enzyme Inhibition—Definitions

Enzyme inhibition Many types of molecule exist which are capable of interfering with the activity of an individual enzyme. Any molecule which acts directly on an enzyme to lower its catalytic rate is called an inhibitor. Some enzyme inhibitors are normal body metabolites that inhibit a particular enzyme as part of the normal metabolic control of a pathway. Other inhibitors may be foreign substances, such as drugs or toxins, where the effect of enzyme inhibition could be either therapeutic or, at the other extreme, lethal. Enzyme inhibition may be of two main types irreversible or reversible, with reversible inhibition itself being subdivided into competitive and noncompetitive inhibition. Reversible inhibition can be overcome by removing the inhibitor from the enzyme, for example by dialysis (see Topic B6), but this is not possible for irreversible inhibition, by definition. 

Biochemists observe other kinds of enzyme inhibition. Noncompetitive inhibition consists of cases in which an inhibitor combines with either the E or the ES form of the enzyme. This requires definition of two new inhibitor constants ... 

Alternatively we could measure the 1C50 or the Ki (inhibitory constant) for the perpetrator. The A) of a perpetrator that is capable of inhibiting an enzyme (or transporter) is the dissociation constant for the enzyme-inhibitor complex. Accurate estimation of the A) requires, among other things, the appropriate definition or specification of the type of enzyme inhibition (e.g., competitive, noncompetitive, or uncompetitive). The appropriate in vitro experiments require that multiple concentrations of the inhibitor must be used as well as a range of substrate concentrations that embrace the substrate Km, and from these experiments both the type of inhibition elicited by the perpetrator can be deduced and the A) value for the perpetrator can be estimated. The Ki will have units of concentration. Alternatively, K values can be computed from /C50 values for an inhibitor. The /C50 is defined simply as the inhibitor concentration that decreases the biotransformation of a substrate at a single, specified concentration by 50%. This parameter obviously also has units of concentration (e.g., pM), and can be related to the Ki as follows. 

Tannins are, by definition, substances capable of producing stable combinations with proteins and other plant polymers such as polysaccharides. The transformation of animal skins into rotproof leather results from this property, as does astringency, fining and enzyme inhibition. Tannins react with proteins in each instance collagen in tanning. 

Enzyme inhibition data is commonly expressed as 1(50) or Kl. This data can be made a part of the composite lattice. In this way, not only can the lattice act to assess FIT of novel structures, but it can also provide an estimate of Ki for the novel structures. In order to clearly focus on active site binding, the present investigation is limited to the consideration of competitive enzyme inhibitors. However, in principle, the HASL methodology would lend Itself to applications involving less definitive binding as is often encountered in studies where only 1(50) values are available, in cases of unspecified binding to a receptor, or where in vivo data, e.g. percent growth inhibition, are considered. 

Due to the definition of the method, many CoMFA studies and related 3D QSAR analyses, where GRID and other molecular fields are implemented in a CoMFA-like model, deal with the quantitative description of ligand-protein interactions, like enzyme inhibition, e.g. 

In general terms, a modulator is any substance that reversibly interacts with the enzyme modifying its kinetic behavior. Most modulators exert a negative effect and are then considered inhibitors. By definition, an inhibitor is a substance that reversibly interacts with the enzyme reducing its catalytic potential. Most enzymatic reactions of industrial relevance are subjected to product and/or substrate inhibition, so that kinetics of enzyme inhibition is highly relevant. 

Competitive, 249, 123, 146, 190 [partial, 249, 124 progress curve equations for, 249, 176, 180 for three-substrate systems, 249, 133, 136] competitive-uncompetitive, 249, 138 concave-up hyperbolic, 249, 143 dead-end, 249, 124 [for bireactant kinetic mechanism determination, 249, 130-133 definition of kinetic constants, 249, 220-221 effects on enzyme progress curves, nonlinear regression analysis, 249, 71-72 inhibition constant evaluation, 249, 134-135 kinetic analysis with, 249, 123-143 one-substrate systems, 249, 124-126 unireactant systems, theory,... 

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