enzyme

Introduction

enzyme, biological catalyst. The term enzyme comes from zymosis, the Greek word for fermentation, a process accomplished by yeast cells and long known to the brewing industry, which occupied the attention of many 19th-century chemists.

Louis Pasteur recognized in 1860 that enzymes were essential to fermentation but assumed that their catalytic action was inextricably linked with the structure and life of the yeast cell. Not until 1897 was it shown by German chemist Edward Büchner that cell-free extracts of yeast could ferment sugars to alcohol and carbon dioxide; Büchner denoted his preparation zymase. This important achievement was the first indication that enzymes could function independently of the cell.

The first enzyme molecule to be isolated in pure crystalline form was urease, prepared from the jack bean in 1926 by American biochemist J. B. Sumner, who suggested, contrary to prevailing opinion, that the molecule was a protein. In the period from 1930 to 1936, pepsin, chymotrypsin, and trypsin were successfully crystallized; it was confirmed that the crystals were protein, and the protein nature of enzymes was thereby firmly established.

Enzyme Deficiency

A variety of metabolic diseases are now known to be caused by deficiencies or malfunctions of enzymes. Albinism, for example, is often caused by the absence of tyrosinase, an enzyme essential for the production of cellular pigments. The hereditary lack of phenylalanine hydroxylase results in the disease phenylketonuria (PKU) which, if untreated, leads to severe mental retardation in children.

Identification and Classification

More than 1,500 different enzymes have now been identified, and many have been isolated in pure form. Hundreds have been crystallized, and the amino acid sequences and three-dimensional structure of a significant number have been fully determined through the technique of X-ray crystallography. The knowledge gained has led to great progress in understanding the mechanisms of enzyme chemistry. Biochemists categorize enzymes into six main classes and a number of subclasses, depending upon the type of reaction involved. The 124-amino acid structure of ribonuclease was determined in 1967, and two years later the enzyme was synthesized independently at two laboratories in the United States.

Enzymatic Action

Like all catalysts, enzymes accelerate the rates of reactions while experiencing no permanent chemical modification as a result of their participation. Enzymes can accelerate, often by several orders of magnitude, reactions that under the mild conditions of cellular concentrations, temperature, pH, and pressure would proceed imperceptibly (or not at all) in the absence of the enzyme. The efficiency of an enzyme's activity is often measured by the turnover rate, which measures the number of molecules of compound upon which the enzyme works per molecule of enzyme per second. Carbonic anhydrase, which removes carbon dioxide from the blood by binding it to water, has a turnover rate of 10⁶. That means that one molecule of the enzyme can cause a million molecules of carbon dioxide to react in one second.

Most enzymatic reactions occur within a relatively narrow temperature range (usually from about 30℃ to 40℃), a feature that reflects their complexity as biological molecules. Each enzyme has an optimal range of pH for activity; for example, pepsin in the stomach has maximal reactivity under the extremely acid conditions of pH 1–3. Effective catalysis also depends crucially upon maintenance of the molecule's elaborate three-dimensional structure. Loss of structural integrity, which may result from such factors as changes in pH or high temperatures, almost always leads to a loss of enzymatic activity. An enzyme that has been so altered is said to be denatured (see denaturation).

Consonant with their role as biological catalysts, enzymes show considerable selectivity for the molecules upon which they act (called substrates). Most enzymes will react with only a small group of closely related chemical compounds; many demonstrate absolute specificity, having only one substrate molecule which is appropriate for reaction.

Numerous enzymes require for efficient catalytic function the presence of additional atoms of small nonprotein molecules. These include coenzyme molecules, many of which only transiently associate with the enzyme. Nonprotein components tightly bound to the protein are called prosthetic groups. The region on the enzyme molecule in close proximity to where the catalytic event takes place is known as the active site. Prosthetic groups necessary for catalysis are usually located there, and it is the place where the substrate (and coenzymes, if any) bind just before reaction takes place.

The side-chain groups of amino acid residues making up the enzyme molecule at or near the active site participate in the catalytic event. For example, in the enzyme trysin, its complex tertiary structure brings together a histidine residue from one section of the molecule with glycine and serine residues from another. The side chains of the residues in this particular geometry produce the active site that accounts for the enzyme's reactivity.

Bibliography

See J. E. and E. T. Bell, Proteins and Enzymes (1988).

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