ENZYMES

Enzymes are molecules that act as critical catalysts in biological systems. Catalysts are substances that increase the rate of chemical reactions without being consumed in the reaction. Without enzymes, many reactions would require higher levels of energy and higher temperatures than exist in biological systems. Enzymes are proteins that possess specific binding sites for other molecules (substrates). A series of weak binding interactions allow enzymes to accelerate reaction rates. Enzyme kinetics is the study of enzymatic reactions and mechanisms. Enzyme inhibitor studies have allowed researchers to develop therapies for the treatment of diseases, including AIDS.

French chemist Louis Pasteur (1822–1895) was an early investigator of enzyme action. Pasteur hypothesized that the conversion of sugar into alcohol by yeast was catalyzed by "ferments," which he thought could not be separated from living cells. In 1897, German biochemist Eduard Buchner (1860–1917) isolated the enzymes that catalyze the fermentation of alcohol from living yeast cells. In 1909, English physician Sir Archibald Garrod (1857–1936) first characterized enzymes genetically through the one gene-one enzyme hypothesis. Garrod studied the human disease alkaptonuria, a hereditary disease characterized by the darkening of excreted urine after exposure to air. He hypothesized that alkaptonurics lack an enzyme that breaks down alkaptans to normal excretion products, that alkaptonurics inherit this inability to produce a specific enzyme, and that they inherit a mutant form of a gene from each of their parents and have two mutant forms of the same gene. Thus, he hypothesized, some genes contain information to specify particular enzymes.

The early twentieth century saw dramatic advancement in enzyme studies. German chemist Emil Fischer (1852–1919) recognized the importance of substrate shape for binding by enzymes. German-American biochemist Leonor Michaelis (1875–1949) and Canadian biologist Maud Menten (1879–1960) introduced a mathematical approach for quantifying enzyme-catalyzed reactions. American chemists James Sumner (1887–1955) and John Northrop (1891–1987) were among the first to produce highly ordered enzyme crystals and firmly establish the proteinaceous nature of these biological catalysts. In 1937, German-born British biochemist Hans Krebs (1900–1981) postulated how a series of enzymatic reactions were coordinated in the citric acid cycle for the production of ATP from glucose metabolites. Today, enzymology is a central part of biochemical study, and the fields of industrial microbiology and genetics employ enzymes in numerous ways, from food production to gene cloning, to advanced therapeutic techniques.

Enzymes are proteins that encompass a large range of molecular size and mass. They may be composed of more than one polypeptide chain. Each polypeptide chain is called a subunit and may have a separate catalytic function. Some enzymes require non-protein groups for enzymatic activity. These components include metal ions and organic molecules called coenzymes. Coenzymes that are tightly or covalently attached to enzymes are termed prosthetic groups. Prosthetic groups contain critical chemical groups which allow the overall catalytic event to occur.

Enzymes bind their substrates at special folds and clefts in their structures called active sites. Because active sites have chemical groups precisely located and orientated for binding the substrate, they generally display a high degree of substrate specificity. The active site of an enzyme consists of two key regions, the catalytic site, which interacts with the substrate during the reaction, and the binding site, the chemical groups of the enzyme that bind the substrate, allowing the interactions at the catalytic site to occur. The crevice of the active site creates a microenvironment whose properties are critical for catalysis. Environmental factors influencing enzyme activity include pH, polarity and hydrophobicity of amino acids in the active site, and a precise arrangement of the chemical groups of the enzyme and its substrate.

Enzymes have high catalytic power, high substrate specificity, and are generally most active in aqueous solvents at mild temperature and physiological pH. Most enzymes catalyze the transfer of electrons, atoms, or groups of atoms. There are thousands of known enzymes, but most can be categorized according to their biological activities into six major classes: oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.

Enzymes generally have an optimum pH range in which they are most active. The pH of the environment will affect the ionization state of catalytic groups at the active site and the ionization of the substrate. Electrostatic interactions are therefore controlled by pH. The pH of a reaction may also control the conformation of the enzyme by influencing amino acids critical for the three-dimensional shape of the macromolecule.

Inhibitors can diminish the activity of an enzyme by altering the binding of substrates. Inhibitors may resemble the structure of the substrate, thereby binding the enzyme and competing for the correct substrate. Inhibitors may be large organic molecules, small molecules, or ions. They can be used for chemotherapeutic treatment of diseases.

Regulatory enzymes are characterized by increased or decreased activity in response to chemical signals. Metabolic pathways are regulated by controlling the activity of one or more enzymatic steps along that path. Regulatory control allows cells to meet changing demands for energy and metabolites.