B.2 Models of Enzyme Activity

• Enzymes are very large molecules – usually comprised of well over a hundred amino acids.

• -  Human maltase for example, which can be extracted from liver cells, has over nine hundred amino acids coupled together by peptide bonds to form its intricate three-dimensional structure.

• -  Using the modern techniques of X-Ray diffraction, researchers are able to see the shapes of enzymes like these, and can tag the substrates so they can view the molecular combinations.

• -  As precise as this is, the exact behaviour of the E-S complexes during a reaction cannot be viewed.

• -  Models have been developed and are used to illustrate and help one visualize the structure of enzymes and how they are believed to function.

• -  In 1894 Emil Fischer, a German chemist proposed the analogy of a lock and a key to help explain the physical relationship between an enzyme and its substrate.
  o This analogy , which has since become known as the“Lock and Key Model”, states that a substrate and an enzyme fit together like a key fits into a lock.
  o The visual this creates is useful because it emphasizes that each component in the reaction must have the correct shape and fit together perfectly for a reaction to occur.
  o The result of an enzymatic reaction is to change the substrate, but the enzyme (lock) remains intact and may be used repeatedly.

• To take this comparison one step further, the size and shape of the key hole is significant as not all keys will fit into a given lock – and even if a key will fit through a key hole, it may still not unlock the lock because it is not the right shape to match the mechanism inside the lock.

• -  In enzyme language, the particular location where the substrate joins the enzyme is called the active site. The combination of specific amino acids in this region determines its exact shape and chemical nature.

• -  Not only must a molecule have the right shape and size to match an active site in order to unite it and form an E-S complex, it must also match it chemically if the reaction is going to take place.

• -  When this happens, the combined arrangement is referred to as an activated E-S complex.

• -  The lock and key analogy has the short-coming of presenting enzymes and substrates as being solid, rigid structures, where it is believed that the nature of molecules and chemical bonds give them some flexibility.

• The Induced Fit Hypothesis is an extension of the analogy that takes this aspect into account.

  o It is believed that as the E-S complex forms, the combining of the substrate into the active site forces slight changes in the shapes of the molecules.

  oAs in the maltose/maltase examples, maltase is very large and has an abundance of H-bonds that allow it to flex.

  oThis elasticity is limited because of other bonds that maintain it stertiary structure.

• o The presence of maltose in the active site induces as light shape change in the protein that puts stress back onto maltose. This distorts the shape of the disaccharide and breaks the bond holding the two monosaccharides together as one molecule.

  o The two glucose molecules that result do not properly fit the active site. They become dislodged and are released.

• Maltase, now free of the sugars and chemically unaltered, regains its original shape.

• Enzymes are not significantly affected by reactions and they are available to be used again.

• -  The formation of activated E-S complexes is critical in these types of reactions. Without them, the reactions will not take place.

• -  This model to explain the mechanics of enzyme activity can be further extended. It is possible for a substance other than the substrate to fit into an active site.

o Should this happen, the configuration of this combination is not exact due to the

similar, but incorrect, “reactant”. No reaction will proceed and the reaction that could have occurred will be blocked because of a non-substrate (an inhibitor) is occupying the active site.

o In other words, a substrate-like substance can inhibit an enzymatic reaction. This is the same as a wrong key fitting into a lock and being unable to open it.

The physical structures of proteins are essential for reactions, but even these huge polypeptides require the presence of other substances to function properly.

o The protein component of an enzyme is known as the apoenzyme. These polymers often rely on smaller, non-protein substances called cofactor, which either become attached to, or otherwise associate with, the protein, enabling it to unite with the substrate.

o When this happens, the whole complex (consisting of a protein with its cofactors) is termed a holoenzyme, but for its simplicity’s sake, these entire combinations are just referred to as enzymes.

- There are two distinctly different types of cofactors:
o metal ion activators and coenzymes.
o During a reaction, every time a chemical bond breaks or is formed, there is an

impact on the electron distribution in the molecules involved.
o The presence of metal ion activators such as K+ and Zn2+ add stability to the

molecules during these electron shifts.

- Coenzymes, on the other hand, are usually organic complexes that are synthesized in cells from vitamins.
o One example of a coenzyme is NAD (nicotinamide adenine dinucleotide), which is

derived from niacin, one of the B vitamins.
o NAD transports hydrogen to and from reactions as required, and is commonly

known as a hydrogen carrier as a result.
o Another coenzyme, simply called Coenzyme A, which is also derived from a B

vitamin, is critical in cellular reactions that generate ATP.