- Related Topics:
- enzyme
- transcription factor
- interferon
- prion
- protein phosphorylation
- Notable Honorees:
- Rodney Robert Porter
Some enzymes help to break down large nutrient molecules, such as proteins, fats, and carbohydrates, into smaller molecules. This process occurs during the digestion of foodstuffs in the stomach and intestines of animals. Other enzymes guide the smaller, broken-down molecules through the intestinal wall into the bloodstream. Still other enzymes promote the formation of large, complex molecules from the small, simple ones to produce cellular constituents. Enzymes are also responsible for numerous other functions, which include the storage and release of energy, the course of reproduction, the processes of respiration, and vision. They are indispensable to life.
Each enzyme is able to promote only one type of chemical reaction. The compounds on which the enzyme acts are called substrates. Enzymes operate in tightly organized metabolic systems called pathways. A seemingly simple biological phenomenon—the contraction of a muscle, for example, or the transmission of a nerve impulse—actually involves a large number of chemical steps in which one or more chemical compounds (substrates) are converted to substances called products; the product of one step in a metabolic pathway serves as the substrate for the succeeding step in the pathway.
The role of enzymes in metabolic pathways can be illustrated diagrammatically. The chemical compound represented by A (see diagram below) is converted to product E in a series of enzyme-catalyzed steps, in which intermediate compounds represented by B, C, and D are formed in succession. They act as substrates for enzymes represented by 2, 3, and 4. Compound A may also be converted by another series of steps, some of which are the same as those in the pathway for the formation of E, to products represented by G and H.
The letters represent chemical compounds; numbers represent enzymes that catalyze individual reactions. The relative heights represent the thermodynamic energy of the compounds (e.g., compound A is more energy-rich than B, B more energy-rich than C). Compounds A, B, etc., change very slowly in the absence of a catalyst but do so rapidly in the presence of catalysts 1, 2, 3, etc.
The regulatory role of enzymes in metabolic pathways can be clarified by using a simple analogy: that between the compounds, represented by letters in the diagram, and a series of connected water reservoirs on a slope. Similarly, the enzymes represented by the numbers are analogous to the valves of the reservoir system. The valves control the flow of water in the reservoir; that is, if only valves 1, 2, 3, and 4 are open, the water in A flows only to E, but, if valves 1, 2, 5, and 6 are open, the water in A flows to G. In a similar manner, if enzymes 1, 2, 3, and 4 in the metabolic pathway are active, product E is formed, and, if enzymes 1, 2, 5, and 6 are active, product G is formed. The activity or lack of activity of the enzymes in the pathway therefore determines the fate of compound A; i.e., it either remains unchanged or is converted to one or more products. In addition, if products are formed, the activity of enzymes 3 and 4 relative to that of enzymes 5 and 6 determines the quantity of product E formed compared with product G.
Both the flow of water and the activity of enzymes obey the laws of thermodynamics; hence, water in reservoir F cannot flow freely to H by opening valve 7, because water cannot flow uphill. If, however, valves 1, 2, 5, and 7 are open, water flows from F to H, because the energy conserved during the downhill flow of water through valves 1, 2, and 5 is sufficient to allow it to force the water up through valve 7. In a similar way, enzymes in the metabolic pathway cannot convert compound F directly to H unless energy is available; enzymes are able to utilize energy from energy-conserving reactions in order to catalyze reactions that require energy. During the enzyme-catalyzed oxidation of carbohydrates to carbon dioxide and water, energy is conserved in the form of an energy-rich compound, adenosine triphosphate (ATP). The energy in ATP is utilized during an energy-consuming process such as the enzyme-catalyzed contraction of muscle.
Because the needs of cells and organisms vary, not only the activity but also the synthesis of enzymes must be regulated; e.g., the enzymes responsible for muscular activity in a leg muscle must be activated and inhibited at appropriate times. Some cells do not need certain enzymes; a liver cell, for example, does not need a muscle enzyme. A bacterium does not need enzymes to metabolize substances that are not present in its growth medium. Some enzymes, therefore, are not formed in certain cells, others are synthesized only when required, and still others are found in all cells. The formation and activity of enzymes are regulated not only by genetic mechanisms but also by organic secretions (hormones) from endocrine glands and by nerve impulses. Small molecules also play an important role (see below Enzyme flexibility and allosteric control).
If an enzyme is defective in some respect, disease may occur. The enzymes represented by the numbers 1 to 4 in the diagram must function during the conversion of the starting substance A to the product E. If one step is blocked because an enzyme is unable to function, product E may not be formed; if E is necessary for some vital function, disease results. Many inherited diseases and conditions of humans result from a deficiency of one enzyme. Some of these are listed in the table. Albinism, for example, results from an inherited lack of ability to synthesize the enzyme tyrosinase, which catalyzes one step in the pathway by which the pigment for hair and eye color is formed.
| Enzymes identified with hereditary diseases | |
| disease name | defective enzyme |
| albinism | tyrosinase |
| phenylketonuria | phenylalanine hydroxylase |
| fructosuria | fructokinase |
| methemoglobinemia | methemoglobin reductase |
| galactosemia | galactose-1-phosphate uridyl transferase |
Other functions
Enzymes play an increasingly important role in medicine. The enzyme thrombin is used to promote the healing of wounds. Other enzymes are used to diagnose certain kinds of disease, to cause the remission of some forms of leukemia—a disease of the blood-forming organs—and to counteract unfavorable reactions in people who are allergic to penicillin. The enzyme lysozyme, which destroys cell walls, is used to kill bacteria. Enzymes have also been investigated for their potential to prevent tooth decay and to serve as anticoagulants in the treatment of thrombosis, a disease characterized by the formation of a clot, or plug, in a blood vessel. Enzymes may eventually be used to control enzyme deficiencies and abnormalities resulting from diseases.
It might also be noted in passing that enzymes are used in industrial processes involving the preparation of certain chemical compounds and the tanning of leather. They also are valuable in analytical procedures involving the detection of very small quantities of specific substances. Enzymes are necessary in various food-related industries, including cheese making, the brewing of beer, the aging of wine, and the baking of bread. Enzymes also may be used to clean clothes. For some industrial uses of enzymes, see baking.
General properties
Classification and nomenclature
The first enzyme name, proposed in 1833, was diastase. Sixty-five years later, French microbiologist and chemist Émile Duclaux suggested that all enzymes be named by adding -ase to a root indicative of the nature of the substrate of the enzyme. Although enzymes are no longer named in such a simple manner, with the exception of a few—e.g., pepsin, trypsin, chymotrypsin, papain—most enzyme names do end in -ase.
Any systematic classification of enzymes should be based on a common property or quality that varies sufficiently to be useful as a distinguishing feature. In this regard, three properties of enzymes could serve as a basis for enzyme classification—the exact chemical nature of the enzyme, the chemical nature of the substrate, and the nature of the reaction catalyzed. In addition, although, as indicated above, early attempts at enzyme classification were based on the nature of broad groups of substrates (e.g., enzymes called carbohydrases act on carbohydrates), close functional similarities among enzymes in different groups were often obscured. By general agreement, enzymes now are classified according to their substrates and the nature of the reaction they catalyze.
In an attempt to devise a rational system of enzyme nomenclature, two names are given to an enzyme. One, known as the systematic name, is based on logical principles but is often long and awkward; the other, “trivial” name is short and generally used but not usually exact or systematic. In the scheme of systematic nomenclature, six main groups of enzymatic reactions are recognized; each catalyzes one reaction type and is subdivided on the basis of detailed definitions of the reaction catalyzed and of the substrate involved in the reaction. Enzymes that catalyze reactions in which hydrogen is transferred belong to the group known as oxidoreductases; those that catalyze the introduction of the elements of water at a specific site in a molecule are called hydrolases. The other four groups of reactions are the transferases—which catalyze reactions in which substances other than hydrogen are transferred—the lyases, the isomerases, and the ligases. Oxidoreductases and transferases account for about 50 percent of the approximately 1,000 enzymes recognized thus far. The table lists a few enzymes, their trivial names, their systematic names, and their biological roles.
| Classification of some enzymes | ||||
|---|---|---|---|---|
|
*Based on recommendations (1964) of the International Union of Biochemistry. **The numbering system is as follows: the first number places the enzyme in one of six general groups—1, oxidoreductases; 2, transferases; 3, hydrolases; 4, lyases; 5, iomerases; and 6, ligases. The second number places the enzyme in a subclass based on substrate type or reaction type; e.g., the enzyme may act on molecules with −CHOH groups. The third number places the enzyme in a subsubclass, which specifies the reaction type more fully; e.g., NAD coenzyme required. The fourth number is the serial number of the enzyme in its subsubclass. ***NAD and NADH represent the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD), respectively; ATP and ADP represent adenosine triphosphate and adenosine diphosphate, respectively. | ||||
| systematic name* | trivial name | reaction catalyzed | biological role | |
| code number** | name*** | |||
| 1.1.1.1 | alcohol: NAD oxidoreductase | alcohol dehydrogenase | alcohol + NAD → acetaldehyde NADH | alcoholic fermentation |
| 1.1.1.27 | L-lactate: NAD oxidoreductase | lactic dehydrogenase | lactate + NAD → pyruvate + NADH | carbohydrate metabolism |
| 2.7.1.40 | ATP: pyruvate phosphotransferase | pyruvate kinase | pyruvic acid + ATP → phosphoenolpyruvic acid + ADP | carbohydrate metabolism |
| 3.1.1.7 | acetylcholine: acetylhydrolase | acetylcholinesterase | acetylcholine + H2O → acetate + choline | nerve-impulse conduction |
Chemical nature
Little was known about the chemical nature of enzymes until the beginning of the 20th century, although scientists were almost convinced that they were proteins. In 1926 the enzyme urease was the first to be crystallized and clearly identified as a protein. Within the next few years the digestive enzymes pepsin, trypsin, and chymotrypsin were shown to be proteins. Since that time hundreds of enzymes, all of them proteins, have been prepared and characterized by chemical methods. Much of the knowledge of protein chemistry has, in fact, resulted from studies involving enzymes and from attempts to understand their nature and mode of action.
Although some enzymes consist of a single chain of the amino acids (i.e., simple organic molecules containing nitrogen), most enzymes are composed of more than one chain. Each chain is called a subunit. Many enzymes have two, four, or six subunits, and some consist of as many as 12 to 60 subunits. In many cases the subunits have identical structures; in others, however, several different types of subunit chains are involved.
With the exception of proteins that act as structural elements, most of the proteins in physiologically active tissues such as kidney and liver are enzymes. Regardless of the exact amount of enzymatic protein in an organism, it is clear that hundreds of different enzymes must be present in each tissue to account for the myriad reactions composing metabolism.
