Enzymes

Enzymes, are the most extraordinary and highly specialized proteins.Enzymes have extraordinary catalytic power, often far greater than that of synthetic or inorganic catalysts.They have a high degree of specificity for their substrates,they accelerate chemical reactions tremendously, and they function in aqueous solutions under very mild conditions of temperature and pH. Few nonbiological catalysts have all these properties.

Enzymes accelerate reactions by factors of as much as a million or more. Indeed, most reactions in biological systems do not take place at observable rates in the absence of enzymes. Even a reaction as simple as the hydration of carbon dioxide is catalyzed by an enzyme namely, carbonic anhydrase. The transfer of CO2 from the tissues into the blood and then to the alveolar (air sac in the lung) air would be less complete in the absence of this enzyme. In fact, carbonic anhydrase is one of the fastest enzymes known. Each enzyme molecule can hydrate 106 molecules of CO2 per second.

This catalyzed reaction is 107 times as fast as the uncatalyzed one. Enzymes are highly specific both in the reactions that they catalyze and in their choice of reactants, which are called substrates.

An enzyme usually catalyzes a single chemical reaction or a set of closely related reactions.

Side reactions leading to the wasteful formation of by-products are rare in enzyme-catalyzed reactions, in contrast with uncatalyzed ones.

Enzymes are central to every biochemical process.

Acting in organized sequences, they catalyze the hundreds of stepwise reactions that degrade nutrient molecules, conserve and transform chemical energy, and make biological macromolecules from simple precursors.

Through the action of regulatory enzymes, metabolic pathways are highly coordinated to yield a tuneful interplay among the many activities necessary to sustain life.

The study of enzymes has immense practical importance.In some diseases, especially inheritable genetic disorders, there may be a deficiency or even a total absence of one or more enzymes. For other disease conditions, excessive activity of an enzyme may be the cause. Measurements of the activities of enzymes in blood plasma, erythrocytes, or tissue samples are important in diagnosing certain illnesses.

Many drugs exert their biological effects through interactions with enzymes. And enzymes are important practical tools, not only in medicine but in the chemical industry, food processing, and agriculture.

History of Enzyme Biological catalysis was first recognized and described in the late 1700s, in studies on the digestion of meat by secretions of the stomach, and research continued in the 1800s with examinations of the conversion of starch to sugar by saliva and various plant extracts.

In the 1850s, Louis Pasteur concluded that fermentation of sugar into alcohol by yeast is catalyzed by ferments.

He postulated that these ferments were inseparable from the structure of living yeast cells Then in 1897 Eduard Buchner discovered that yeast extracts could ferment sugar to alcohol, proving that fermentation was promoted by molecules that continued to function when removed from cells Frederick W. Khne called these molecules enzymes.

The isolation and crystallization of urease by James Sumner in 1926 provided a breakthrough in early enzyme studies. Sumner found that urease crystals consisted entirely of protein, and he postulated that all enzymesare proteins.In the absence of other examples, this idea remained controversial for some time. Only in the 1930s was Sumners conclusion widely accepted, after John Northrop and Moses Kunitz crystallized pepsin, trypsin, and other digestive enzymes and found them also to be proteins

With the exception of a small group of catalytic RNA molecules , all enzymes are proteins. Their catalytic activity depends on the integrity of their native protein conformation. If an enzyme is denatured or dissociated into its subunits, catalytic activity is usually lost. If an enzyme is broken down into its component amino acids, its catalytic activity is always destroyed.Thus the primary, secondary, tertiary, and quaternary structures of protein enzymes are essential to their catalytic activity.

Enzymes, like other proteins, have molecular weights ranging from about 12,000 to more than 1 million.Some enzymes require no chemical groups for activity other than their amino acid residues. Others require an additional chemical component called a cofactoreither one or more inorganic ions, such as Fe2+, Mg2+, Mn2+, or Zn2+

A complex organic or metalloorganic molecule called a coenzyme OR Cofactors that are small organic molecules are called coenzymes.

Coenzymes are often derived from vitamins, it can be either tightly or loosely bound to the enzyme.

If tightly bound, they are called prosthetic groups.

Loosely associated coenzymes are more like cosubstrates because they bind to and are released from the enzyme just as substrates and products are.

The use of the same coenzyme by a variety of enzymes and their source in vitamins sets coenzymes apart from normal substrates,

However, enzymes that use the same coenzyme are usually mechanistically similar

Classification of enzymeEnzymes Are Classified on the Basis of the Types of Reactions That They CatalyzeTo bring some consistency to the classification of enzymes, in 1964 the International Union of Biochemistry established an Enzyme Commission to develop a nomenclature for enzymes. Reactions were divided into six major groups numbered 1 through 6

These groups were subdivided and further subdivided, so that a four-digit number preceded by the letters EC for Enzyme Commission could precisely identify all enzymes

Consider as an example nucleoside monophosphate (NMP) kinase. It catalyzes the following reaction:

NMP kinase transfers a phosphoryl group from ATP to NMP to form a nucleoside diphosphate (NDP) and ADPConsequently, it is a transferase, or member of group 2. Many groups in addition to phosphoryl groups, such as sugars and carbon units, can be transferred.

Transferases that shift a phosphoryl group are designated 2.7. Various functional groups can accept the phosphoryl group. If a phosphate is the acceptor, the transferase is designated 2.7.4.

The final number designates the acceptor more precisely. In regard to NMP kinase, a nucleoside monophosphate is the acceptor, and the enzyme's designation is EC 2.7.4.4. Although the common names are used routinely, the classification number isused when the precise identity of the enzyme might be ambiguous.

Kinetics of enzyme catalyzed reactionsThe formation of an enzyme-substrate complex is the first step in enzymatic catalysisEmil Fischer's proposed the lock and key model in 1890, in this model the active site of the unbound enzyme is complementary in shape to the substrate

Induced-Fit Model of Enzyme-Substrate Binding In this model, the enzyme changes shape on substratebinding. The active site forms a shape complementary to the substrate only after the substrate has been bound.

Evidences for the existence of an enzyme-substrate complexAt a constant concentration of enzyme, the reaction rate increases with increasing substrate concentration until a maximal velocity is reached. In contrast, uncatalyzed reactions do not show this saturation effect. The fact that an enzyme-catalyzed reaction has a maximal velocity suggests the formation of a distinct ES complex

X-ray crystallography has provided high-resolution images of substrates and substrate analogs bound to the active sites of many enzymes

Spectroscopic characteristics of many enzymes and substrates change on formation of an ES complex

Tryptophan synthetase, a bacterial enzyme that contains a pyridoxal phosphate (PLP) prosthetic group.

This enzyme catalyzes the synthesis of l-tryptophan from l-serine and indole-derivative. The addition of l-serine to the enzyme produces a marked increase in the fluorescence of the PLP group The subsequent addition of indole, the secondsubstrate, reduces this fluorescence to a level even lower than that of the enzyme alone.

Active siteThe active site of an enzyme is the region that binds the substrates (and the cofactor, if any). It also contains the residues that directly participate in the making and breaking of bonds. These residues are called the catalytic groups. Thus, the interaction of the enzyme and substrate at the active site promotes the formation of the transition state

The active site is a three-dimensional cleft formed by groups that come from different parts of the amino acidsequence indeed, residues far apart in the sequence may interact more strongly than adjacent residues in the aminoacid sequence. In lysozyme, an enzyme that degrades the cell walls of some bacteria, the important groups in the activesite are contributed by residues numbered 35, 52, 62, 63, 101, and 108 in the sequence of the 129 amino acids