Enzyme-substrate complex

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Enzyme-Substrate (ES) complexes are formed during enzyme catalysed chemical reactions.

Contents

Formation

There are two key theories on how enzyme-substrate complexes form: the Lock and Key model or the Induced Fit model. Most ES complexes form in a way which is a mixture of these two models as the two models illustrate the extremes of how ES complexes form.

What happens in ES Complexes

Every enzyme is equipt with a 'cleft' in its structure, which is complementary to a particular substrate. This is known as the active site. As well as shape, the specificity of the active site is developed further via the amino acid R-Groups within the site. These groups will interact specifically with the substrate molecule(s). The ES complex is the state in, which the active site of the enzyme is non-covalently bound to the substrate molecule(s). This is where the chemical reaction occurs:

ENZYME + SUBSTRATE -> ENZYME SUBSTRATE COMPLEX -> ENZYME + PRODUCT

The enzyme can perform its catalysis mechanism on the substrate only when it is in the enzyme-substrate complex. It is in this structure that the enzyme is able to increase the rate of the reaction either by causing bond distortion or polarisation to lower the activation energy, creating an alternative pH environment for the substrate within the active site which are the optimum conditions for that reaction, locating the substrates close to each other to make contact (and so the reaction) more likely or by creating an alternative state with the substrate as this alternative transition state has a lower activation to be overcome in order to allow the reaction to continue[1].

Effect on the Rate of Reaction

The enzyme is normally involved in a rate limiting step of a reaction as the Enzyme-Substrate complex provides an alternative transition state for the reaction path to follow. This means that a reaction will occur at its maximum rate when there's a maximum number of ES complexes formed (i.e. no empty active sites). This is the stage at which Vmax is reached and a further increase in substrate concentration from this point on will not affect the Initial Rate anymore[2].

Enzyme Inhibitors

Enzyme InhibitorsInhibitors of enzymes normally affect the ES complex. They can affect the ES complex in a number of ways, such as: by preventing the formation of the ES complex (competitive and irreversible inhibitors) or they prevent the catalytic activity of the enzyme once in the ES complex (non competitive and uncompetitive inhibitors). This shows how important the formation of enzyme-substrate complexes are for many biological processes as enzyme inhibitors are a major area for drug development[3]. Drugs such as Penicillin, Aspirin, Tamiflu and many more are examples of the medications used to treat to disease which act as inhibitors on certain enzymes.

Calculations involving the Enzyme-Substrate Complex

The Michaelis-Menten kinetics are closely linked to enzyme-substrate complexes as they allow the values of Vmax and Km (the Michaelis - Menten constatnt) to be calculated. Km illustrates the value of the substrate concentration when exactly half of the enzymes involved in the enzyme-linked reaction are occupied in enzyme-substrate complexes. A low value of Km illustrates an enzyme with a high affinity for its substrate as only a low concentration of substrate is required to fill half the active sites of the enzymes[4].

Further information

The following is a useful video demonstrating the formation of an Enzyme Substrate Complex: www.youtube.com/watch

References

  1. J.M. Berg, J.L. Tymoczko, G.J. Gattor Jnr, L. Stryer; Biochemistry (8th Edition); New York; W.H. Freemand and Company; 2015
  2. Martin Chaplin; Enzyme Technology - Simple Kinetics of Enzyme Action; 2004 (updated 2014); cited: 01/12/17; available at: http://www1.lsbu.ac.uk/water/enztech/kinetics.html
  3. J.M. Berg, J.L. Tymoczko, G.J. Gatto Jnr, L. Stryer; Biochemistry (8th Edition); New York, W.H. Freeman and Company; 2015
  4. J.M. Berg, J.L. Tymoczko, G.J. Gatto Jnr, L. Stryer; Biochemistry (8th Edition); New York, W.H. Freeman and Company; 2015
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