Classification of Enzymes

For many years it was the custom to classify enzymes solely by the reactions which they catalyzed. As already noted there is within living systems an amazing variety of chemical reactions and these many diverse reactions are specifically catalyzed by individual enzymes. However, as the chemical composition of enzymes becomes better understood, there is an increasing tendency to classify enzymes not merely in terms of what they do but also in terms of their true chemical composition.

In the first place it is possible to characterize a large group of enzymes as hydrolyzing enzymes or hydrolases. The hydrolases are concerned primarily with the breaking down and the building up of proteins, carbohydrates and lipids. It is a characteristic of these essential organic materials that their large molecules are built up by a progressive subtraction of water molecules. When amino acids unite, the acid group of one amino acid combines with the basic amino group of a second, and as in typical acid-base reactions, water is split off. In this way protein molecules are built up, and if they are to be broken down to amino acids again, water molecules must be added. Similarly, when an alcohol unites with an organic acid to form an ester, water is split off; and in the reverse process by the addition of water an ester may be converted into an acid and an alcohol. Thus by the addition of water, a fat may be hydrolyzed to fatty acid and the trivalent alcohol glycerol. When two molecules of a simple sugar such as dextrose unite to form a disaccharide, then also water is split off, and with the addition of water the double sugar may be broken into simple sugars again. Similarly starch is formed from sugar by a series of reactions in which water is removed. All of these reactions in which water is removed or added are catalyzed by the hydrolases. Proteolytic enzymes break down proteins to polypeptids and amino acids (or build up proteins from such compounds), lipases split fats into fatty acids and glycerol (or synthesize the fats from the fatty acids and glycerol), amylase acts on starch, sucrase (often called invertase) acts on sucrose, and there are other specific enzymes which act on the various isomers of sucrose. The hydrolases also include the lecithinases which split off fatty acids from the rest of the lecithin molecule, and the phosphatases. The latter split off phosphate from organic combination. Thus one phosphatase breaks glycerol phosphate into glycerol and phosphate; another group of phosphatase enzymes, the nucleotidases, break nucleotides into nucleosides and phosphoric acid. Most hydrolases are concerned primarily with the breakdown of large molecules as it occurs in digestion and with the synthesis of the breakdown products to form large molecules again in the cells. Such reactions are of primary importance in nutrition, but they yield little energy.

In addition to the hydrolases concerned primarily with nutrition, there are some hydrolases which play a part in other vital phenomena. Thus the enzyme cholinesterase, which hydrolyzes acetylcholine into choline and acetic acid, is believed to have great importance for nervous function. Another hydrolase enzyme which has excited great interest is hyaluronidase. This breaks down hyaluronic acid, a polysaccharide that tends to hold cells together. The enzyme is found in various bacteria; also in testis extracts. When skin is treated with hyaluronidase, the cells separate sufficiently to permit the spreading between them of substances like India ink. Heparin, like hyaluronic acid, is a mucopolysaccharide. There is apparently a heparinase which breaks up heparin or at least destroys its activity. Mention has already been made of the enzymes which specifically attack ribonucleic acid and desoxyribonucleic acid. These likewise are hydrolases.

The enzymes which cause coagulation or clotting, thrombin and rennin, may also be hydrolases. Thrombin causes clotting of vertebrate blood and rennin clots milk. They may both produce this effect as a result of proteolytic action.

Similar to the hydrolases are the phosphorylases. These enzymes, which should not be confused with the phosphatases, add phosphoric acid instead of water. They are very important in carbohydrate metabolism and will be discussed later in this connection.

Enzymes which act on inorganic pyrophosphates and hydrolyze them to orthophosphates are called pyrophosphatases. (This is a reaction which occurs even without the aid of enzymes.) Pyrophosphatases are found in many different types of living material.

In addition to the hydrolases there are various other categories of enzymes. There are enzymes which transfer a radical or group from one substance, the donor, to another, the acceptor. These have been called transferases, and they include the transaminases, which transfer amino groups; and the phosphokinases, which transfer phosphate groups.

An interesting enzyme found especially in the red blood cells of higher animals, is carbonic anhydrase. This catalyzes the reaction in which carbonic acid is split into carbon dioxide and water. Actually, the reaction is speeded in both directions, so that carbonic acid can be formed more rapidly as well as broken down. The reaction needs to be speeded in order to hasten the gain or loss of carbon dioxide from the blood.