Term Paper on Enzyme Inhibition | Enzymes | Biomolecules | Biology

Here is a term paper on ‘Enzyme Inhibition’. Find paragraphs, long and short term papers on the ‘Meaning and Types of Enzyme Inhibition’ especially written for school and college students.

Term Paper # 1. Meaning of 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 cellular 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, but this is not possible for irreversible inhibition, by definition.

Term Paper # 2. Types of Enzyme Inhibition:

i. Irreversible Inhibition:

Inhibitors which bind irreversibly to an enzyme often form a covalent bond to an amino acid residue at or near the active site, and permanently inactivate the enzyme. Susceptible amino acid residues include Ser and Cys residues which have reactive – OH and – SH groups, respectively.

The compound diisopropyl-phosphofluoridate (DIPF), a component of nerve gases, reacts with a Ser-residue in the active site of the enzyme acetyl­cholinesterase, irreversibly inhibiting the enzyme and preventing the transmission of nerve impulses. Iodoacetamide modifies Cys residues and hence may be used as a diagnostic tool in determining whether one or more Cys residues are required for enzyme activity.

The antibiotic penicillin irreversibly inhibits the glycopeptide transpeptidase enzyme that forms the cross-links in the bacterial cell wall by covalently attaching to a Ser-residue in the active site of the enzyme.

ii. Reversible Competitive Inhibition:

A competitive inhibitor typically has close structural similarities to the normal substrate for the enzyme. Thus it competes with substrate molecules to bind to the active site. The enzyme may bind either a substrate molecule or an inhibitor molecule, but not both at the same time. The competitive inhibitor binds reversibly to the active site.

At high substrate concentrations the action of a competitive inhibitor is overcome because a sufficiently high substrate concentration will successfully compete out the inhibitor molecule in binding to the active site. Thus there is no change in the V_max of the enzyme but the apparent affinity of the enzyme for its substrate decreases in the presence of the competitive inhibitor, and hence K_m increases.

A good example of competitive inhibition is provided by succinate dehydrogenase. This enzyme uses succinate as its substrate and is competitively inhibited by malonate which differs from succinate in having one rather than two methylene groups. Many drugs work by mimicking the structure of the substrate of a target enzyme, and hence act as competitive inhibitors of the enzyme.

Competitive inhibition can be recognized by using a Lineweaver Burk plot. V₀ is measured at different substrate concentrations in the presence of a fixed concentration of inhibitor. A competitive inhibitor increases the slope of the line on the Lineweaver-Burk plot, and alters the intercept on the x-axis (since K_m is increased), but leaves the intercept on the y-axis unchanged (since V_max remains constant).

iii. Reversible Noncompetitive Inhibition:

A noncompetitive inhibitor binds reversibly at a site other than the active site and causes a change in the overall three- dimensional shape of the enzyme that leads to a decrease in catalytic activity. Since the inhibitor binds at a different site to the substrate, the enzyme may bind the inhibitor, the substrate or both the inhibitor and substrate together.

The effects of a non­competitive inhibitor cannot be overcome by increasing the substrate concentration, so there is a decrease in V_max. In noncompetitive inhibition the affinity of the enzyme for the substrate is unchanged and so K_m remains the same. An example of noncompetitive inhibition is the action of pepstatin on the enzyme renin.

Noncompetitive inhibition can be recognized on a Lineweaver Burk plot, since it increases the slope of the experimental line, and alters the intercept on the y-axis (since V_max is decreased), but leaves the intercept on the x-axis unchanged (since K_m remains constant).