Enzyme Inhibitors

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[[Enzyme|Enzyme]] Inhibitors are substances that reduce the rate of enzyme activity in an enzyme [[Catalysed reaction|catalysed reaction]]&nbsp;<ref>Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref>. These substances may be in the form of [[Molecule|molecules]] or ions that mimic the actual substrates in order to bind to the active site of the enzyme to form an enzyme-inhibitor (EI) complex. Enzyme inhibitors are of two types;
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[[Enzyme|Enzyme]] Inhibitors are substances that reduce the rate of enzyme activity in an enzyme [[Catalysed reaction|catalysed reaction]]&nbsp;<ref>Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref>. These substances may be in the form of [[Molecule|molecules]] or ions that mimic the actual substrates in order to bind to the active site of the enzyme to form an enzyme-inhibitor (EI) complex. Enzyme inhibitors are of two types:
  
 
#Irreversible Inhibitors  
 
#Irreversible Inhibitors  
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=== <u></u>Irreversible Inhibitors<u></u>  ===
 
=== <u></u>Irreversible Inhibitors<u></u>  ===
  
<u></u>These substances bind permanently to an amino acid side chain (commonly Ser or Cys) at or near the [[Enzyme active site|active site]] of an enzyme to form an EI complex. The binding permanently inactivates the enzyme by changing the shape of it so substrates can no longer bind. This interraction usually occurs via a strong [[Covalent bond|covalent bond]] between the enzyme and the inhibitor. It may also occur via a strong non-covalent linkage. In Irreversible inhibition, the separation of the inhibitor from the active site is usually very slow because of the strong covalent linkage that exist between the inhibitor and the enzyme. Irreversible inhibitors are used in pharmaceuticals for the synthesis of drugs. An example is the inhibition of [[Acetylcholinesterase|acetylcholinesterase]] by Sarin gas which reacts with the [[Hydroxyl group|hydroxyl group]] of [[Serine|serine]] residue in the enzyme to form an [[Ester|ester]]. This prevents the breakdown of [[Acetylcholine|acetylcholines]] by acetylcholinesterase.  
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<u></u>These substances bind permanently to an amino acid side chain (commonly Serine or Cysteine) at or near the [[Enzyme active site|active site]] of an enzyme to form an EI complex. The binding permanently inactivates the enzyme by changing the shape of it so substrates can no longer bind. This interraction usually occurs via a strong [[Covalent bond|covalent bond]] between the enzyme and the inhibitor. It may also occur via a strong non-covalent linkage. In irreversible inhibition, the separation of the inhibitor from the active site is usually very slow because of the strong covalent linkage that exist between the inhibitor and the enzyme. Irreversible inhibitors are used in pharmaceuticals for the synthesis of drugs. An example is the inhibition of [[Acetylcholinesterase|acetylcholinesterase]] by sarin gas which reacts with the [[Hydroxyl group|hydroxyl group]] of [[Serine|serine]] residue in the enzyme to form an [[Ester|ester]]. This prevents the breakdown of [[Acetylcholine|acetylcholines]] by acetylcholinesterase.  
  
 
=== Reversible Inhibitors  ===
 
=== Reversible Inhibitors  ===
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=== <u></u>Reversible-competitive Inhibitor<u></u>  ===
 
=== <u></u>Reversible-competitive Inhibitor<u></u>  ===
  
In this type of inhibition,the formation of the EI complex prevents the binding of a substrate. The inhibitor compete with the substrate for the [[Enzyme active site|active site]]&nbsp;because they have similar shapes&nbsp;and this therefore lowers the rate of enzyme catalysed reaction by reducing the number of active sites available to bind other substrate molecules. This can be overcome by increasing the substrate concentration until the inhibitor dissociates from the enzyme active site. They are mostly used as therapeutic agents,&nbsp;e.g.&nbsp;If our body has an inflammatory response to a certain stimuli, then Ibroprofen can be used as it is a competitive inhibitor of the enzymes involved in the signaling pathways of the inflammatory response. Competitive&nbsp;Inhibitors cause [[Km|K<sub><span style="font-size: 11px;">m</span></sub>]]&nbsp;to increase and [[Vmax|V<sub>max</sub>]] to remain the same&nbsp;<ref name="same">Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref>.  
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In this type of inhibition, the formation of the EI complex prevents the binding of a substrate. The inhibitor compete with the substrate for the [[Enzyme active site|active site]]&nbsp;because they have similar shapes&nbsp;and this therefore lowers the rate of enzyme catalysed reaction by reducing the number of active sites available to bind other substrate molecules. This can be overcome by increasing the substrate concentration until the inhibitor dissociates from the enzyme active site. They are mostly used as therapeutic agents,&nbsp;e.g. if our body has an inflammatory response to a certain stimuli, then Ibroprofen can be used as it is a competitive inhibitor of the enzymes involved in the signaling pathways of the inflammatory response. Competitive inhibitors cause [[Km|K<sub><span style="font-size: 11px;">m</span></sub>]]&nbsp;to increase and [[Vmax|V<sub>max</sub>]] to remain the same&nbsp;<ref name="same">Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref>.  
  
 
=== <u></u>Reversible-Non-competitive Inhibitor<u></u>  ===
 
=== <u></u>Reversible-Non-competitive Inhibitor<u></u>  ===
  
<u></u>These molecules bind away from the active site of an enzyme and modifies the shape of the active site. This does not effect the affinity of which the substrate is bound (ie. Km remains unaltered). It can also bind to an already existing enzyme-substrate (ES) complex. This type of inhibition cannot be overcome by increasing the substrate concentration like reversible-competitive inhibition.Non-competitive inhibitor reduces the number of substrate molecules that can be converted to products by one enzyme molecule in 1 second i.e the [[Turnover number|turnover number]] (Kcat).&nbsp;Non-competitive inhibitors&nbsp;have no effect&nbsp;on&nbsp;K<span style="font-size: 11px;">m</span>&nbsp;but V<sub>max</sub> is lowered&nbsp;<ref name="same">Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref>.  
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<u></u>These molecules bind away from the active site of an enzyme and modifies the shape of the active site. This does not effect the affinity of which the substrate is bound (i.e. Km remains unaltered). It can also bind to an already existing enzyme-substrate (ES) complex. This type of inhibition cannot be overcome by increasing the substrate concentration like reversible-competitive inhibition. Non-competitive inhibitor reduces the number of substrate molecules that can be converted to products by one enzyme molecule in 1 second i.e the [[Turnover number|turnover number]] (Kcat).&nbsp;Non-competitive inhibitors&nbsp;have no effect&nbsp;on&nbsp;K<span style="font-size: 11px;">m</span>&nbsp;but V<sub>max</sub> is lowered&nbsp;<ref name="same">Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref>.  
  
 
=== Reversible-Uncompetitive-Inhibitor  ===
 
=== Reversible-Uncompetitive-Inhibitor  ===
  
<u></u>These substances binds only to an already existing enzyme-substrate complex. Once bound to the enzyme-substrate complex the enzyme-substrate-inhibitor complex, ESI&nbsp;complex, will take a very long time to produce any product. They attach to the ES complex away from the active site. Uncompetitive inhibition essentially decreases the concentration of functional enzymes.Like Non-competitive inhibition,uncompetitive inhibition cannot be overcome by increasing the substrate concentration. As the concentration of substrate increases, this increases the rate of inhibition. Uncompetitive inhibitors decrease both K<sub>M</sub> and V<sub>max.</sub>&nbsp;<ref name="same">Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref><ref>Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref>.  
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<u></u>These substances binds only to an already existing enzyme-substrate complex. Once bound to the enzyme-substrate complex the enzyme-substrate-inhibitor complex, ESI&nbsp;complex, will take a very long time to produce any product. They attach to the ES complex away from the active site. Uncompetitive inhibition essentially decreases the concentration of functional enzymes.nLike Non-competitive inhibition, uncompetitive inhibition cannot be overcome by increasing the substrate concentration. As the concentration of substrate increases, this increases the rate of inhibition. Uncompetitive inhibitors decrease both K<sub>M</sub> and V<sub>max.</sub>&nbsp;<ref name="same">Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref><ref>Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.</ref>.  
  
 
=== References  ===
 
=== References  ===
  
 
<references />&nbsp;<br><br>
 
<references />&nbsp;<br><br>

Revision as of 20:00, 30 November 2015

Enzyme Inhibitors are substances that reduce the rate of enzyme activity in an enzyme catalysed reaction [1]. These substances may be in the form of molecules or ions that mimic the actual substrates in order to bind to the active site of the enzyme to form an enzyme-inhibitor (EI) complex. Enzyme inhibitors are of two types:

  1. Irreversible Inhibitors
  2. Reversible Inhibitors

Contents

Irreversible Inhibitors

These substances bind permanently to an amino acid side chain (commonly Serine or Cysteine) at or near the active site of an enzyme to form an EI complex. The binding permanently inactivates the enzyme by changing the shape of it so substrates can no longer bind. This interraction usually occurs via a strong covalent bond between the enzyme and the inhibitor. It may also occur via a strong non-covalent linkage. In irreversible inhibition, the separation of the inhibitor from the active site is usually very slow because of the strong covalent linkage that exist between the inhibitor and the enzyme. Irreversible inhibitors are used in pharmaceuticals for the synthesis of drugs. An example is the inhibition of acetylcholinesterase by sarin gas which reacts with the hydroxyl group of serine residue in the enzyme to form an ester. This prevents the breakdown of acetylcholines by acetylcholinesterase.

Reversible Inhibitors

These substances bind to the active of an enzyme to form an EI complex. These bonds are not as strong as that of irreversible inhibitors and this causes a separation of the EI complex. Reversible inhibitors are of three types:

Reversible-competitive Inhibitor

In this type of inhibition, the formation of the EI complex prevents the binding of a substrate. The inhibitor compete with the substrate for the active site because they have similar shapes and this therefore lowers the rate of enzyme catalysed reaction by reducing the number of active sites available to bind other substrate molecules. This can be overcome by increasing the substrate concentration until the inhibitor dissociates from the enzyme active site. They are mostly used as therapeutic agents, e.g. if our body has an inflammatory response to a certain stimuli, then Ibroprofen can be used as it is a competitive inhibitor of the enzymes involved in the signaling pathways of the inflammatory response. Competitive inhibitors cause Km to increase and Vmax to remain the same [2].

Reversible-Non-competitive Inhibitor

These molecules bind away from the active site of an enzyme and modifies the shape of the active site. This does not effect the affinity of which the substrate is bound (i.e. Km remains unaltered). It can also bind to an already existing enzyme-substrate (ES) complex. This type of inhibition cannot be overcome by increasing the substrate concentration like reversible-competitive inhibition. Non-competitive inhibitor reduces the number of substrate molecules that can be converted to products by one enzyme molecule in 1 second i.e the turnover number (Kcat). Non-competitive inhibitors have no effect on Km but Vmax is lowered [2].

Reversible-Uncompetitive-Inhibitor

These substances binds only to an already existing enzyme-substrate complex. Once bound to the enzyme-substrate complex the enzyme-substrate-inhibitor complex, ESI complex, will take a very long time to produce any product. They attach to the ES complex away from the active site. Uncompetitive inhibition essentially decreases the concentration of functional enzymes.nLike Non-competitive inhibition, uncompetitive inhibition cannot be overcome by increasing the substrate concentration. As the concentration of substrate increases, this increases the rate of inhibition. Uncompetitive inhibitors decrease both KM and Vmax. [2][3].

References

  1. Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.
  2. 2.0 2.1 2.2 Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.
  3. Berg J., Tymoczko J and Stryer L. (2007) Biochemistry, 6th edition, New York: W.H. Freeman and Company, pg227.
 

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