What enzymes are and how they bind substrates

Enzymes are biological catalysts: they speed up chemical reactions in living things. They are very specific (each works on particular substances), very powerful, and come out of the reaction unchanged, ready to work again. Almost all are proteins; a few are catalytic RNAs, called ribozymes.

Many enzymes need a non-protein helper, a cofactor:

• A coenzyme, an organic molecule often made from a vitamin: NAD from niacin, FAD from riboflavin.
• A metal ion: Zn²⁺ in carbonic anhydrase, Mg²⁺ in DNA polymerase.

The protein part alone is the apoenzyme; the enzyme together with its cofactor is the holoenzyme. A cofactor that is bound tightly is a prosthetic group.

In 1964 the IUB sorted enzymes into six classes by the kind of reaction they carry out: oxidoreductases (oxidation-reduction), transferases (move a group), hydrolases (split using water), lyases (remove groups, making double bonds), isomerases (rearrange a molecule) and ligases (join two molecules, using ATP). A seventh class, translocases, was added later. Different forms of an enzyme that catalyse the same reaction but have different structures are isozymes: hexokinase has four, and lactate dehydrogenase (LDH) five.

The substrate binds in a small pocket on the enzyme, the active site, held by weak bonds. Two models explain the fit:

• Lock and key (Fischer, 1894): the active site is already exactly shaped for its substrate, as only the right key opens a lock.
• Induced fit (Koshland, 1958): the substrate makes the active site change shape around it, like a hand going into a glove.

Enzymes differ in how specific they are: group specificity (a family of related substrates), absolute specificity (only one substrate), stereo-specificity (only one mirror-image form, as D-amino acid oxidase acts only on D-amino acids) and geometrical specificity (only the cis or the trans form, as fumarase).