Explain Why Enzymes Are Specific Explain Why Enzymes Can Be Reused Over and Over Again

A central task of proteins is to human activity equally enzymes—catalysts that increase the charge per unit of virtually all the chemical reactions within cells. Although RNAs are capable of catalyzing some reactions, most biological reactions are catalyzed past proteins. In the absence of enzymatic catalysis, near biochemical reactions are and then deadening that they would not occur under the mild conditions of temperature and pressure that are compatible with life. Enzymes accelerate the rates of such reactions by well over a million-fold, so reactions that would take years in the absence of catalysis can occur in fractions of seconds if catalyzed by the appropriate enzyme. Cells incorporate thousands of different enzymes, and their activities determine which of the many possible chemical reactions actually accept place within the prison cell.

The Catalytic Activity of Enzymes

Like all other catalysts, enzymes are characterized by 2 cardinal properties. Outset, they increase the rate of chemic reactions without themselves existence consumed or permanently altered past the reaction. Second, they increase reaction rates without altering the chemic equilibrium between reactants and products.

These principles of enzymatic catalysis are illustrated in the following instance, in which a molecule acted upon past an enzyme (referred to as a substrate [S]) is converted to a product (P) equally the result of the reaction. In the absenteeism of the enzyme, the reaction tin be written as follows:

The chemical equilibrium between S and P is determined by the laws of thermodynamics (every bit discussed further in the next section of this chapter) and is represented past the ratio of the forrad and opposite reaction rates (South→P and P→Due south, respectively). In the presence of the appropriate enzyme, the conversion of S to P is accelerated, simply the equilibrium between S and P is unaltered. Therefore, the enzyme must accelerate both the forward and reverse reactions equally. The reaction tin exist written as follows:

Note that the enzyme (E) is not altered by the reaction, then the chemical equilibrium remains unchanged, determined solely by the thermodynamic properties of S and P.

The effect of the enzyme on such a reaction is all-time illustrated by the free energy changes that must occur during the conversion of Due south to P (Figure two.22). The equilibrium of the reaction is determined by the last free energy states of Due south and P, which are unaffected past enzymatic catalysis. In order for the reaction to go along, however, the substrate must first be converted to a higher energy state, called the transition land. The energy required to reach the transition state (the activation free energy) constitutes a bulwark to the progress of the reaction, limiting the rate of the reaction. Enzymes (and other catalysts) act by reducing the activation energy, thereby increasing the rate of reaction. The increased rate is the aforementioned in both the forrard and reverse directions, since both must pass through the same transition land.

Effigy 2.22

Energy diagrams for catalyzed and uncatalyzed reactions. The reaction illustrated is the uncomplicated conversion of a substrate South to a product P. Because the final energy land of P is lower than that of S, the reaction proceeds from left to right. For the (more...)

The catalytic action of enzymes involves the bounden of their substrates to course an enzyme-substrate complex (ES). The substrate binds to a specific region of the enzyme, chosen the active site. While jump to the active site, the substrate is converted into the product of the reaction, which is then released from the enzyme. The enzyme-catalyzed reaction can thus be written as follows:

Note that E appears unaltered on both sides of the equation, then the equilibrium is unaffected. However, the enzyme provides a surface upon which the reactions converting S to P can occur more than readily. This is a result of interactions between the enzyme and substrate that lower the energy of activation and favor germination of the transition state.

Mechanisms of Enzymatic Catalysis

The bounden of a substrate to the active site of an enzyme is a very specific interaction. Active sites are clefts or grooves on the surface of an enzyme, usually composed of amino acids from different parts of the polypeptide chain that are brought together in the tertiary structure of the folded protein. Substrates initially demark to the active site by noncovalent interactions, including hydrogen bonds, ionic bonds, and hydrophobic interactions. Once a substrate is bound to the active site of an enzyme, multiple mechanisms can accelerate its conversion to the product of the reaction.

Although the simple example discussed in the previous section involved only a single substrate molecule, well-nigh biochemical reactions involve interactions betwixt two or more different substrates. For case, the formation of a peptide bond involves the joining of ii amino acids. For such reactions, the binding of two or more substrates to the active site in the proper position and orientation accelerates the reaction (Effigy ii.23). The enzyme provides a template upon which the reactants are brought together and properly oriented to favor the formation of the transition state in which they interact.

Effigy 2.23

Enzymatic catalysis of a reaction between two substrates. The enzyme provides a template upon which the two substrates are brought together in the proper position and orientation to react with each other.

Enzymes accelerate reactions besides past altering the conformation of their substrates to approach that of the transition state. The simplest model of enzyme-substrate interaction is the lock-and-key model, in which the substrate fits precisely into the agile site (Effigy two.24). In many cases, however, the configurations of both the enzyme and substrate are modified by substrate binding—a process chosen induced fit. In such cases the conformation of the substrate is contradistinct so that information technology more than closely resembles that of the transition state. The stress produced past such distortion of the substrate can further facilitate its conversion to the transition state by weakening disquisitional bonds. Moreover, the transition land is stabilized past its tight binding to the enzyme, thereby lowering the required energy of activation.

Figure ii.24

Models of enzyme-substrate interaction. (A) In the lock-and-key model, the substrate fits precisely into the active site of the enzyme. (B) In the induced-fit model, substrate binding distorts the conformations of both substrate and enzyme. This distortion (more than...)

In addition to bringing multiple substrates together and distorting the conformation of substrates to arroyo the transition country, many enzymes participate direct in the catalytic procedure. In such cases, specific amino acid side chains in the active site may react with the substrate and class bonds with reaction intermediates. The acidic and basic amino acids are often involved in these catalytic mechanisms, every bit illustrated in the following discussion of chymotrypsin every bit an instance of enzymatic catalysis.

Chymotrypsin is a member of a family of enzymes (serine proteases) that digest proteins past catalyzing the hydrolysis of peptide bonds. The reaction can be written as follows:

The different members of the serine protease family (including chymotrypsin, trypsin, elastase, and thrombin) have singled-out substrate specificities; they preferentially cleave peptide bonds adjacent to different amino acids. For case, whereas chymotrypsin digests bonds adjacent to hydrophobic amino acids, such as tryptophan and phenylalanine, trypsin digests bonds next to basic amino acids, such every bit lysine and arginine. All the serine proteases, however, are like in construction and use the same mechanism of catalysis. The active sites of these enzymes contain 3 critical amino acids—serine, histidine, and aspartate—that bulldoze hydrolysis of the peptide bail. Indeed, these enzymes are chosen serine proteases because of the central role of the serine remainder.

Substrates demark to the serine proteases by insertion of the amino acid adjacent to the cleavage site into a pocket at the active site of the enzyme (Figure 2.25). The nature of this pocket determines the substrate specificity of the different members of the serine protease family unit. For example, the binding pocket of chymotrypsin contains hydrophobic amino acids that interact with the hydrophobic side bondage of its preferred substrates. In contrast, the binding pocket of trypsin contains a negatively charged acidic amino acid (aspartate), which is able to class an ionic bail with the lysine or arginine residues of its substrates.

Figure ii.25

Substrate bounden by serine proteases. The amino acid adjacent to the peptide bail to be cleaved is inserted into a pocket at the agile site of the enzyme. In chymotrypsin, the pocket binds hydrophobic amino acids; the binding pocket of trypsin contains (more than...)

Substrate binding positions the peptide bond to be cleaved adjacent to the active site serine (Figure 2.26). The proton of this serine is so transferred to the active site histidine. The conformation of the active site favors this proton transfer because the histidine interacts with the negatively charged aspartate residue. The serine reacts with the substrate, forming a tetrahedral transition country. The peptide bond is then broken, and the C-terminal portion of the substrate is released from the enzyme. However, the N-terminal peptide remains bound to serine. This situation is resolved when a water molecule (the second substrate) enters the active site and reverses the preceding reactions. The proton of the water molecule is transferred to histidine, and its hydroxyl group is transferred to the peptide, forming a second tetrahedral transition state. The proton is then transferred from histidine back to serine, and the peptide is released from the enzyme, completing the reaction.

Figure 2.26

Catalytic mechanism of chymotrypsin. Three amino acids at the active site (Ser-195, His-57, and Asp-102) play critical roles in catalysis.

This instance illustrates several features of enzymatic catalysis; the specificity of enzyme-substrate interactions, the positioning of unlike substrate molecules in the agile site, and the involvement of active-site residues in the formation and stabilization of the transition state. Although the thousands of enzymes in cells catalyze many dissimilar types of chemical reactions, the same bones principles apply to their operation.

Coenzymes

In improver to binding their substrates, the agile sites of many enzymes demark other small molecules that participate in catalysis. Prosthetic groups are small molecules bound to proteins in which they play critical functional roles. For example, the oxygen carried by myoglobin and hemoglobin is bound to heme, a prosthetic group of these proteins. In many cases metal ions (such as zinc or iron) are bound to enzymes and play fundamental roles in the catalytic procedure. In addition, various low-molecular-weight organic molecules participate in specific types of enzymatic reactions. These molecules are called coenzymes because they work together with enzymes to enhance reaction rates. In contrast to substrates, coenzymes are not irreversibly altered by the reactions in which they are involved. Rather, they are recycled and can participate in multiple enzymatic reactions.

Coenzymes serve as carriers of several types of chemic groups. A prominent case of a coenzyme is nicotinamide adenine dinucleotide (NAD ⁺), which functions as a carrier of electrons in oxidation-reduction reactions (Figure 2.27). NAD⁺ can accept a hydrogen ion (H⁺) and ii electrons (e^-) from i substrate, forming NADH. NADH can and so donate these electrons to a 2d substrate, re-forming NAD⁺. Thus, NAD⁺ transfers electrons from the starting time substrate (which becomes oxidized) to the second (which becomes reduced).

Figure 2.27

Role of NAD⁺ in oxidation-reduction reactions. (A) Nicotinamide adenine dinucleotide (NAD⁺) acts as a carrier of electrons in oxidation-reduction reactions by accepting electrons (due east^-) to form NADH. (B) For instance, NAD⁺ can accept electrons from one substrate (more...)

Several other coenzymes also human activity every bit electron carriers, and still others are involved in the transfer of a variety of additional chemical groups (eastward.thou., carboxyl groups and acyl groups; Tabular array 2.1). The same coenzymes function together with a variety of different enzymes to catalyze the transfer of specific chemical groups between a wide range of substrates. Many coenzymes are closely related to vitamins, which contribute part or all of the structure of the coenzyme. Vitamins are not required by leaner such as Eastward. coli but are necessary components of the diets of human being and other higher animals, which take lost the ability to synthesize these compounds.

Regulation of Enzyme Action

An of import characteristic of about enzymes is that their activities are not constant simply instead tin can exist modulated. That is, the activities of enzymes can be regulated so that they function appropriately to encounter the varied physiological needs that may ascend during the life of the jail cell.

One common type of enzyme regulation is feedback inhibition, in which the product of a metabolic pathway inhibits the activity of an enzyme involved in its synthesis. For example, the amino acrid isoleucine is synthesized past a series of reactions starting from the amino acid threonine (Effigy 2.28). The first step in the pathway is catalyzed by the enzyme threonine deaminase, which is inhibited past isoleucine, the finish product of the pathway. Thus, an adequate amount of isoleucine in the prison cell inhibits threonine deaminase, blocking farther synthesis of isoleucine. If the concentration of isoleucine decreases, feedback inhibition is relieved, threonine deaminase is no longer inhibited, and additional isoleucine is synthesized. By then regulating the action of threonine deaminase, the prison cell synthesizes the necessary amount of isoleucine but avoids wasting energy on the synthesis of more than isoleucine than is needed.

Figure 2.28

Feedback inhibition. The first step in the conversion of threonine to iso-leucine is catalyzed by the enzyme threonine deaminase. The activeness of this enzyme is inhibited past isoleucine, the end product of the pathway.

Feedback inhibition is one example of allosteric regulation, in which enzyme activity is controlled past the binding of small molecules to regulatory sites on the enzyme (Effigy 2.29). The term "allosteric regulation" derives from the fact that the regulatory molecules demark not to the catalytic site, merely to a distinct site on the poly peptide (allo= "other" and steric= "site"). Binding of the regulatory molecule changes the conformation of the protein, which in plow alters the shape of the agile site and the catalytic activeness of the enzyme. In the case of threonine deaminase, binding of the regulatory molecule (isoleucine) inhibits enzymatic activity. In other cases regulatory molecules serve every bit activators, stimulating rather than inhibiting their target enzymes.

Effigy two.29

Allosteric regulation. In this example, enzyme activeness is inhibited by the bounden of a regulatory molecule to an allosteric site. In the absence of inhibitor, the substrate binds to the active site of the enzyme and the reaction proceeds. The bounden (more...)

The activities of enzymes can also be regulated by their interactions with other proteins and past covalent modifications, such every bit the addition of phosphate groups to serine, threonine, or tyrosine residues. Phosphorylation is a specially common mechanism for regulating enzyme action; the add-on of phosphate groups either stimulates or inhibits the activities of many different enzymes (Figure two.30). For example, muscle cells respond to epinephrine (adrenaline) by breaking down glycogen into glucose, thereby providing a source of energy for increased muscular action. The breakdown of glycogen is catalyzed past the enzyme glycogen phosphorylase, which is activated by phosphorylation in response to the bounden of epinephrine to a receptor on the surface of the muscle cell. Protein phosphorylation plays a fundamental role in controlling not but metabolic reactions merely likewise many other cellular functions, including cell growth and differentiation.

Figure 2.30

Protein phosphorylation. Some enzymes are regulated by the improver of phosphate groups to the side-chain OH groups of serine (as shown here), threonine, or tyrosine residues. For example, the enzyme glycogen phosphorylase, which catalyzes the conversion (more...)

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Source: https://www.ncbi.nlm.nih.gov/books/NBK9921/

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