Enzymes Can Be Used Over and Over Again

A fundamental task of proteins is to human action as enzymes—catalysts that increase the rate of virtually all the chemical reactions within cells. Although RNAs are capable of catalyzing some reactions, most biological reactions are catalyzed by proteins. In the absence of enzymatic catalysis, most biochemical reactions are and then wearisome that they would non occur under the balmy conditions of temperature and pressure that are compatible with life. Enzymes accelerate the rates of such reactions by well over a meg-fold, and then reactions that would take years in the absence of catalysis can occur in fractions of seconds if catalyzed by the advisable enzyme. Cells comprise thousands of different enzymes, and their activities make up one's mind which of the many possible chemical reactions really take place within the cell.

The Catalytic Action of Enzymes

Similar all other catalysts, enzymes are characterized by 2 fundamental backdrop. Kickoff, they increase the charge per unit of chemic reactions without themselves being consumed or permanently altered by the reaction. Second, they increment reaction rates without altering the chemical equilibrium between reactants and products.

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

The chemical equilibrium betwixt S and P is adamant by the laws of thermodynamics (as discussed farther in the next section of this chapter) and is represented by the ratio of the forward and reverse reaction rates (Southward→P and P→Southward, respectively). In the presence of the appropriate enzyme, the conversion of Southward to P is accelerated, but the equilibrium between South 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 contradistinct by the reaction, so the chemical equilibrium remains unchanged, determined solely past the thermodynamic backdrop of Due south and P.

The effect of the enzyme on such a reaction is best illustrated by the energy changes that must occur during the conversion of South to P (Figure 2.22). The equilibrium of the reaction is determined past the final energy states of S and P, which are unaffected past enzymatic catalysis. In order for the reaction to continue, however, the substrate must first be converted to a higher energy country, called the transition country. The free energy required to achieve the transition country (the activation free energy) constitutes a barrier 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 frontwards and contrary directions, since both must pass through the same transition state.

Figure 2.22

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

The catalytic activity of enzymes involves the binding of their substrates to form an enzyme-substrate complex (ES). The substrate binds to a specific region of the enzyme, chosen the active site. While bound to the agile site, the substrate is converted into the product of the reaction, which is so 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, so the equilibrium is unaffected. However, the enzyme provides a surface upon which the reactions converting S to P can occur more readily. This is a effect of interactions between the enzyme and substrate that lower the energy of activation and favor formation of the transition state.

Mechanisms of Enzymatic Catalysis

The binding of a substrate to the agile site of an enzyme is a very specific interaction. Agile sites are clefts or grooves on the surface of an enzyme, unremarkably composed of amino acids from different parts of the polypeptide chain that are brought together in the tertiary construction of the folded protein. Substrates initially bind 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 advance its conversion to the product of the reaction.

Although the simple example discussed in the previous department involved just a single substrate molecule, most biochemical reactions involve interactions betwixt two or more different substrates. For example, the germination of a peptide bail involves the joining of two amino acids. For such reactions, the binding of 2 or more substrates to the agile site in the proper position and orientation accelerates the reaction (Effigy two.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 2 substrates are brought together in the proper position and orientation to react with each other.

Enzymes accelerate reactions also by 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 active site (Figure two.24). In many cases, however, the configurations of both the enzyme and substrate are modified by substrate binding—a procedure chosen induced fit. In such cases the conformation of the substrate is altered so that information technology more closely resembles that of the transition state. The stress produced by such distortion of the substrate can further facilitate its conversion to the transition state by weakening critical bonds. Moreover, the transition state is stabilized by its tight binding to the enzyme, thereby lowering the required energy of activation.

Figure two.24

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

In addition to bringing multiple substrates together and distorting the conformation of substrates to approach the transition land, many enzymes participate directly in the catalytic process. In such cases, specific amino acid side bondage 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, as illustrated in the following discussion of chymotrypsin equally an example of enzymatic catalysis.

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

The unlike members of the serine protease family (including chymotrypsin, trypsin, elastase, and thrombin) have distinct substrate specificities; they preferentially carve peptide bonds next to different amino acids. For example, whereas chymotrypsin digests bonds adjacent to hydrophobic amino acids, such equally tryptophan and phenylalanine, trypsin digests bonds next to basic amino acids, such every bit lysine and arginine. All the serine proteases, even so, are like in construction and use the same mechanism of catalysis. The agile sites of these enzymes contain three disquisitional amino acids—serine, histidine, and aspartate—that drive hydrolysis of the peptide bond. Indeed, these enzymes are called serine proteases because of the primal function of the serine rest.

Substrates bind 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 (Effigy two.25). The nature of this pocket determines the substrate specificity of the different members of the serine protease family. For case, the binding pocket of chymotrypsin contains hydrophobic amino acids that interact with the hydrophobic side chains of its preferred substrates. In dissimilarity, the binding pocket of trypsin contains a negatively charged acidic amino acrid (aspartate), which is able to form an ionic bond with the lysine or arginine residues of its substrates.

Figure 2.25

Substrate bounden past serine proteases. The amino acid next to the peptide bond to be cleaved is inserted into a pocket at the active site of the enzyme. In chymotrypsin, the pocket binds hydrophobic amino acids; the binding pocket of trypsin contains (more...)

Substrate binding positions the peptide bail to be cleaved side by side to the active site serine (Figure 2.26). The proton of this serine is then transferred to the active site histidine. The conformation of the active site favors this proton transfer considering the histidine interacts with the negatively charged aspartate residue. The serine reacts with the substrate, forming a tetrahedral transition land. The peptide bond is so cleaved, 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 grouping is transferred to the peptide, forming a 2d tetrahedral transition state. The proton is then transferred from histidine dorsum 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 agile site (Ser-195, His-57, and Asp-102) play critical roles in catalysis.

This example illustrates several features of enzymatic catalysis; the specificity of enzyme-substrate interactions, the positioning of different substrate molecules in the active site, and the involvement of agile-site residues in the formation and stabilization of the transition land. Although the thousands of enzymes in cells catalyze many different types of chemical reactions, the same basic principles apply to their performance.

Coenzymes

In add-on to bounden their substrates, the active sites of many enzymes bind other pocket-size molecules that participate in catalysis. Prosthetic groups are small molecules spring to proteins in which they play critical functional roles. For example, the oxygen carried past myoglobin and hemoglobin is bound to heme, a prosthetic group of these proteins. In many cases metal ions (such as zinc or fe) are bound to enzymes and play central roles in the catalytic process. In add-on, 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 chemical groups. A prominent example of a coenzyme is nicotinamide adenine dinucleotide (NAD ⁺), which functions as a carrier of electrons in oxidation-reduction reactions (Effigy 2.27). NAD⁺ tin can accept a hydrogen ion (H⁺) and 2 electrons (east^-) from one substrate, forming NADH. NADH can then donate these electrons to a 2nd substrate, re-forming NAD⁺. Thus, NAD⁺ transfers electrons from the first 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 every bit a carrier of electrons in oxidation-reduction reactions by accepting electrons (e^-) to grade NADH. (B) For example, NAD⁺ can accept electrons from one substrate (more...)

Several other coenzymes also human action equally electron carriers, and still others are involved in the transfer of a variety of additional chemical groups (e.g., carboxyl groups and acyl groups; Tabular array two.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 role or all of the construction of the coenzyme. Vitamins are not required by bacteria such as East. coli just are necessary components of the diets of human and other higher animals, which have lost the ability to synthesize these compounds.

Regulation of Enzyme Activity

An important feature of most enzymes is that their activities are not abiding but instead can be modulated. That is, the activities of enzymes can be regulated so that they function appropriately to meet the varied physiological needs that may ascend during the life of the cell.

One mutual 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 acid isoleucine is synthesized by a series of reactions starting from the amino acrid threonine (Figure 2.28). The commencement step in the pathway is catalyzed past the enzyme threonine deaminase, which is inhibited past isoleucine, the cease product of the pathway. Thus, an adequate amount of isoleucine in the cell inhibits threonine deaminase, blocking further synthesis of isoleucine. If the concentration of isoleucine decreases, feedback inhibition is relieved, threonine deaminase is no longer inhibited, and additional isoleucine is synthesized. Past so regulating the activeness of threonine deaminase, the prison cell synthesizes the necessary amount of isoleucine but avoids wasting energy on the synthesis of more isoleucine than is needed.

Figure 2.28

Feedback inhibition. The start stride 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 by the bounden of pocket-sized molecules to regulatory sites on the enzyme (Effigy 2.29). The term "allosteric regulation" derives from the fact that the regulatory molecules bind not to the catalytic site, merely to a distinct site on the protein (allo= "other" and steric= "site"). Binding of the regulatory molecule changes the conformation of the protein, which in turn alters the shape of the agile site and the catalytic activity of the enzyme. In the example of threonine deaminase, binding of the regulatory molecule (isoleucine) inhibits enzymatic activity. In other cases regulatory molecules serve equally activators, stimulating rather than inhibiting their target enzymes.

Figure two.29

Allosteric regulation. In this instance, enzyme activity is inhibited by the bounden of a regulatory molecule to an allosteric site. In the absenteeism of inhibitor, the substrate binds to the active site of the enzyme and the reaction gain. The bounden (more...)

The activities of enzymes tin also exist regulated past their interactions with other proteins and by covalent modifications, such as the improver of phosphate groups to serine, threonine, or tyrosine residues. Phosphorylation is a especially common mechanism for regulating enzyme activeness; the addition of phosphate groups either stimulates or inhibits the activities of many different enzymes (Effigy ii.xxx). For example, muscle cells respond to epinephrine (adrenaline) past breaking down glycogen into glucose, thereby providing a source of energy for increased muscular activity. The breakdown of glycogen is catalyzed by the enzyme glycogen phosphorylase, which is activated past phosphorylation in response to the binding of epinephrine to a receptor on the surface of the muscle jail cell. Protein phosphorylation plays a central function in decision-making non only metabolic reactions simply too many other cellular functions, including cell growth and differentiation.

Figure two.thirty

Protein phosphorylation. Some enzymes are regulated past the addition 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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