ENZYMES COURSEWORK

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ENZYMES

Enzymes are catalysts. Most are . (A few  enzymes have been discovered and, for some of these, the catalytic activity is in the RNA part rather than the protein part.

Enzymes bind temporarily to one or more of the  of the reaction they catalyze. In doing so, they lower the amount of activation energy needed and thus speed up the reaction.


Examples:

  • Catalase. It catalyzes the decomposition of hydrogen peroxide into water and oxygen.

2H2O2 -> 2H2O + O2 

One molecule of catalase can break 40 million molecules of hydrogen peroxide each second.

  • Carbonic anhydrase. It is found in red blood cells where it catalyzes the reaction

CO2 + H2O <-> H2CO3 

It enables red blood cells to transport carbon dioxide from the tissues to the lungs.

One molecule of carbonic anhydrase can process one million molecules of CO2 each second.

  • Acetylcholinesterase. It catalyzes the breakdown of the  acetylcholine at several types of  as well as at the  - the specialized synapse that triggers the contraction of skeletal muscle.

One molecule of acetylcholinesterase breaks down 25,000 molecules of acetylcholine each second. This speed makes possible the rapid "resetting" of the synapse for transmission of another nerve impulse.

In order to do its work, an enzyme must unite - even if ever so briefly - with at least one of the reactants. In most cases, the forces that hold the enzyme and its substrate are noncovalent, an assortment of:

  •  
  •  
  • and

Most of these interactions are weak and especially so if the atoms involved are farther than about one  from each other. So successful binding of enzyme and substrate requires that the two molecules be able to approach each other closely over a fairly broad surface. Thus the analogy that a substrate molecule binds its enzyme like a key in a lock.

This requirement for complementarity in the configuration of substrate and enzyme explains the remarkable specificity of most enzymes. Generally, a given enzyme is able to catalyze only a single chemical reaction or, at most, a few reactions involving substrates sharing the same general structure.

COMPETITIVE INHABITION

The necessity for a close, if brief, fit between enzyme and substrate explains the phenomenon of competitive inhibition.

One of the enzymes needed for the release of energy within the cell is succinic dehydrogenase.

It catalyzes the oxidation (by the removal of two hydrogen atoms) of succinic acid (a). If one adds malonic acid to cells, or to a test tube mixture of succinic acid and the enzyme, the action of the enzyme is strongly inhibited. This is because the structure of malonic acid allows it to bind to the same site on the enzyme (b). But there is no oxidation so no speedy release of products. The inhibition is called competitive because if you increase the ratio of succinic to malonic acid in the mixture, you will gradually restore the rate of catalysis. At a 50:1 ratio, the two molecules compete on roughly equal terms for the binding (=catalytic) site on the enzyme.

ENZYME COFACTORS

Many enzymes require the presence of an additional, nonprotein, cofactor.

  • Some of these are metal ions such as Zn2+ (the cofactor for carbonic anhydrase), Cu2+, Mn2+, K+, and Na+.
  • Some cofactors are small organic molecules called coenzymes. The B vitamins are precursors of coenzymes.
  •  (B1)
  •  (B2) and

Coenzymes may be covalently bound to the protein part (called the apoenzyme) of enzymes as a prosthetic group. Others bind more loosely and, in fact, may bind only transiently to the enzyme as it performs its catalytic act.

Lysozyme: a model of enzyme action

A number of lysozymes are found in nature; in human tears and egg white, for examples. The enzyme is antibacterial because it degrades the polysaccharide that is found in the cell walls of many bacteria. It does this by catalyzing the insertion of a water molecule at the position indicated by the red arrow. This  breaks the chain at that point.

The bacterial polysaccharide consists of long chains of alternating amino sugars:

  • N-acetylglucosamine (NAG)
  • N-acetylmuramic acid (NAM)

These hexose units resemble glucose except for the presence of the side chains containing amino groups.

Lysozyme is a globular protein with a deep cleft across part of its surface. Six hexoses of the substrate fit into this cleft.

  • With so many oxygen atoms in , as many as 14  form between the six amino sugars and certain amino acid  such as Arg-114, Asn-37, Asn-44, Trp-62, Trp-63, and Asp-101.
  • Some hydrogen bonds also form with the C=O groups of several .
  • In addition, hydrophobic interactions may help hold the substrate in position.

X-ray crystallography has shown that as lysozyme and its substrate unite, each is slightly deformed. The fourth hexose in the chain becomes twisted out of its normal position. This imposes a strain on the C-O bond on the ring-4 side of the oxygen bridge between rings 4 and 5. It is just at this point that the polysaccharide is broken. A molecule of water is inserted between these two hexoses, which breaks the chain. Here, then, is a structural view of what it means to lower activation energy. The energy needed to break this covalent bond is lower now that the atoms connected by the bond have been distorted from their normal position.

As for lysozyme itself, binding of the substrate induces a small (~0.75Å) movement of certain amino acid residues so the cleft closes slightly over its substrate. So the "lock" as well as the "key" changes shape as the two are brought together. (This is sometimes called "induced fit".)

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The amino acid residues in the vicinity of rings 4 and 5 provide a plausible mechanism for completing the catalytic act. Residue 35, glutamic acid (Glu-35), is about 3Å from the -O- bridge that is to be broken. The free carboxyl group of glutamic acid is a hydrogen ion donor and available to transfer H+ to the oxygen atom. This would break the already-strained bond between the oxygen atom and the carbon atom of ring 4.

Now having lost an electron, the carbon atom acquires a positive charge. Ionized carbon is normally very unstable, but the attraction of ...

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