In 1833, Payen and Peroz found that they could take malt (a product of grain used in the brewing industry) and use water to extract a substance that digested and liquefied starch paste. A year later it was found that a similar extract from stomachs could digest meat products, and in 1836 a strange material called 'pepsin' was isolated which could also carry out this digestive process in a test tube ('in vitro').

Decomposition, a phenomenon that previously had been thought to be completely biological, could apparently be brought about by soluble agents extracted from tissue like stomachs or plant material like malt. Just before Mendel's work, in 1860, Berthold discovered a 'soluble ferment' he called invertase that he thought played a role in metabolism and digestion, but few other scientists got very excited.

In general, Mendel and his contemporary scientists believed that metabolism (and digestion) could only take place inside intact cells in the 'protoplasm' that was becoming popular. Even Pasteur supported this idea (as our story shows) by his work on alcoholic fermentation (and the problems caused by bacteria). But when Buchner was finally able to produce a fermentation that was completely free of all cells, and began extracting the agents responsible, it became impossible to ignore the fact that these 'in yeast' agents, enzymes, played an important role in life.

When Sumner purified the enzyme urease from jackbeans in 1926, it became possible to study the structure and chemical properties of these agents. Almost all enzymes are proteins. These polymers of amino acids are folded up into three dimensional shapes. Part of the external shape produced by this folding is the active site, and the shape of this groove or infolding exactly fits the shape of the reacting molecules, which in enzymology are called substrates.

The substrate molecules bind in the active site. Because the shape of the active site and the shape of the reacting molecules fit one another exactly, enzymes are very specific. A particular enzyme will only bind and act on its own substrate, and never bind other molecules or the substrates of other enzymes.

Once the correct substrate has bound at the active site of the enzyme, an enzyme-substrate complex is created. Sometimes the substrate is held in the complex by combinations of electrical attraction, hydrophobic repulsion, or hydrogen bonding between and from the amino acids. Sometimes a covalent bond will link the substrate even more firmly to the complex, but no matter what the mechanism, the result is the same; the reacting molecules are brought close together. This has the same effect as increasing the concentration of reacting molecules by 30,000 to 45,000 times. This alone would increase the effective rate of a chemical reaction.

For many reactions, the orientation of the reacting molecules is very important. Exactly the right parts of each molecule must 'bump' together for the atoms to rearrange themselves into products. Many times only a few bonds need to be changed during the reaction. The rest of the bonds in the reacting molecules stay exactly the same and are unaltered. In these cases, two specific parts of the molecule must interact. Within the enzyme-substrate complex, substrates are oriented in such a way that the parts of the molecules that have to change their bonds are brought into the right relationship.

Physical interaction between the substrate and the active site of the enzyme brings about subtle changes in the forces holding the molecule together. As the reacting molecule binds to the active site, the shape of the molecule can become distorted, bent or twisted. This slight shape change puts a strain on the molecule. A covalent bond that is forced out of shape in this way becomes weaker and more easily broken. It therefore takes less energy to snap the atoms apart and rearrange them. At a practical level, this lowers the amount of extra energy needed to reach the transition state, and thus the amount of extra energy needed to bring about the chemical reaction. The activation energy has been lowered

Enzymes are organic catalysts that have a range of properties.

1. Enzymes increase the rate of chemical reactions.

2. Enzymes are very specific. Cells make a different enzyme to catalyze each and every different chemical reaction taking place within it.

3. Enzymes often need 'helper' molecules called cofactors which work along with the enzyme to help the reacting molecules reach the transition state.

4. The protein part of the enzyme is sensitive to the environment. Proteins undergo shape changes as a result of changes in the environment. This is called denaturation.

   • Proteins are denatured by heat. At high temperatures the protein loses its shape, the active site is lost and the catalytic properties vanish. The enzyme becomes useless.
   • At low temperatures, despite the presence of a catalyst, the rate of the reaction will slow down because there is not enough kinetic energy - the reaction stops.
   • pH also causes proteins to change shape. These changes with changing pH, usually result in fatal denaturation and loss of catalytic function.