Enzyme Inhibition PDF

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Mandatory assignment...

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Define Enzyme Inhibition Compare and contrast competitive, uncompetitive and mixed inhibition Describe the four major methods by which enzymes act

What is Enzyme Inhibition Enzyme inhibition refers to a decrease in enzyme-related processes, enzyme production, or enzyme activity. This process is performed by enzyme inhibitors - Slow/halt enzymatic reactions - Enzyme inhibitors are among one of the most pharmaceutical agents known o Ex. Aspirin, ACE inhibitors Enzyme inhibitors are classified under two categories:  

Reversible Inhibition (ex. Competitive inhibition , Non-Competitive Inhibition and Uncompetitive Inhibition) Irreversible Inhibition (ex. Group specific reagents and reactive substrate analogs)

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Enzyme inhibition refers to a decrease in enzyme-related processes, enzyme production, or enzyme activity. Enzyme inhibitors are molecules that interfere with catalysis, slowing or halting enzymatic reactions. They can essentially modify the catalytic properties of the enzyme and , therefore , slow down the reaction rate or even in some cases stop the catalysis .Such inhibitors work by blocking or distorting the active site. Enzymes catalyze virtually all cellular processes, so it should not be surprising that enzyme inhibitors are among the most important pharmaceutical agents known. For exam example, ple, aspirin (acetylsalic (acetylsalicylate) ylate) inhibits the enzyme that catalyzes the first step in the synthesis of prostaglandins, compounds involved in many processes, including some that produce pain. The study of enzyme inhibitors also has provided valuable information about enzyme mechanisms and has helped define some metabolic pathways. There are two broad classes of enzyme inhibitors: reversible and irreversible. Angiotensin conv converting erting enzyme (ACE) inhibitors block the angiotensin-converting enzyme and therefore inhibit the conversion of angiotensin I into angiotensin II and reduce the synthesis of aldosterone. Rev Reversible ersible Inhibition The process by which the inhibitor binds to the enzyme non-covalently and can dissociate from the enzyme with great ease. Irreversible IInhibition nhibition The process by which the inhibitor can bind either non-covalently or covalently to the enzyme and inhibit its activity. Unlike reversible inhibition, in irreversible inhibition the inhibitor takes a very long time to dissociate from the enzyme.

Types of Enzyme Inhibition There are three known types of enzyme inhibition

(1)Competitive inhibition Compete with substrate for active site on the enzyme Prevents substrate-binding Km is increased but Vmax is not altered . (2) Uncompetitive Inhibition   

 They have separate binding sites but bond only to ES complex  decrease both Vmax and Km. (3) Non-Competitive Inhibition  

Changes shape of enzyme Prevent substrate-binding

(4) Mixed Competitive Inhibition -They have separate binding sites , but bond to E or ES

Competitive Inhibition -A good way to describe this inhibition : It competes with the substrate for the active site of an enzyme This prevents the formation of enzyme-substrate complexes. Therefore, fewer substrate molecules can bind to the enzymes so the reaction rate is decreased. The level of inhibition depends on the relative concentration of substrate and inhibitor.Like I mentioned before this falls under the class of a reversible inhibition. In the case of competitive inhibition, Km is increased but Vmax is not altered. Uncompetitive Inhibit Inhibition ion Uncompetitive inhibitors differ from competitive inhibitors in that they have a separate binding site on the enzyme-substrate complex But they only bind to the enzyme when substrate is bound to the enzyme. Uncompetitive inhibitors decrease both Vmax and Km.

Non-Competitive Inhibi Inhibition tion Due to this binding, it deforms the structure of the enzyme so that it does not form the ES complex at its normal rate, and it prevents the formation of enzyme-product complexes, which leads to fewer product formations. Because they do not compete with substrate molecules, noncompetitive inhibitors are not affected by substrate concentration. -In the case of noncompetitive inhibition, Vmax is lowered but Km is not altered. Mixed Competitive Inhibition In this process,mixed inhibitors bind at a separate site, but may bind to either E or ES.

Competitive & Non-Competitive Inhibition

Image (A) : The substrate can normally bind to the active site of the enzyme Image (B) : Competitive Inhibition: In competitive inhibition the inhibitors essentially interfere with the active site of enzyme so substrate cannot bind Image (C): Uncompetitive Inhibition : The inhibitor binds to the enzyme only after the substrate has bound Image (D): Non-Competitive Inhibition: In non-competitive inhibition the inhibitors essentially change the shape of the enzyme so it cannot bind to the substrate....