Which Three Things Can Alter the Function or Job of an Enzyme?

A cardinal chore of proteins is to act as enzymes—catalysts that increase the rate of virtually all the chemical reactions within cells. Although RNAs are capable of catalyzing some reactions, almost biological reactions are catalyzed by proteins. In the absenteeism of enzymatic catalysis, most biochemical reactions are so slow that they would not occur under the mild conditions of temperature and pressure that are uniform with life. Enzymes accelerate the rates of such reactions by well over a million-fold, so reactions that would accept years in the absenteeism of catalysis can occur in fractions of seconds if catalyzed past the appropriate enzyme. Cells contain thousands of different enzymes, and their activities determine which of the many possible chemical reactions actually take place inside the cell.

The Catalytic Activity of Enzymes

Similar all other catalysts, enzymes are characterized by two fundamental backdrop. Starting time, they increase the rate of chemical reactions without themselves being consumed or permanently altered by the reaction. Second, they increase 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 by 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 between S and P is determined by the laws of thermodynamics (as discussed further in the next section of this chapter) and is represented past the ratio of the forward and opposite reaction rates (S→P and P→S, respectively). In the presence of the appropriate enzyme, the conversion of S to P is accelerated, only the equilibrium between S and P is unaltered. Therefore, the enzyme must accelerate both the forward and reverse reactions equally. The reaction can exist written as follows:

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

The outcome of the enzyme on such a reaction is best illustrated by the free energy changes that must occur during the conversion of Due south to P (Figure 2.22). The equilibrium of the reaction is adamant by the last energy states of S and P, which are unaffected by enzymatic catalysis. In social club for the reaction to keep, however, the substrate must offset be converted to a higher free energy state, called the transition country. The energy required to achieve the transition state (the activation energy) constitutes a barrier to the progress of the reaction, limiting the rate of the reaction. Enzymes (and other catalysts) human activity by reducing the activation energy, thereby increasing the rate of reaction. The increased charge per unit is the same in both the forward and reverse directions, since both must pass through the same transition country.

Figure 2.22

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

The catalytic activeness 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, called the agile site. While bound to the active site, the substrate is converted into the product of the reaction, which is and 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, so the equilibrium is unaffected. Nonetheless, the enzyme provides a surface upon which the reactions converting S to P tin can occur more than readily. This is a result 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 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 unlike parts of the polypeptide chain that are brought together in the third structure of the folded poly peptide. Substrates initially bind to the agile site past noncovalent interactions, including hydrogen bonds, ionic bonds, and hydrophobic interactions. Once a substrate is bound to the agile site of an enzyme, multiple mechanisms tin can advance its conversion to the product of the reaction.

Although the simple example discussed in the previous section involved only a single substrate molecule, most biochemical reactions involve interactions between ii or more different substrates. For example, the germination of a peptide bond involves the joining of 2 amino acids. For such reactions, the bounden of 2 or more substrates to the active site in the proper position and orientation accelerates the reaction (Figure 2.23). The enzyme provides a template upon which the reactants are brought together and properly oriented to favor the germination of the transition state in which they interact.

Effigy ii.23

Enzymatic catalysis of a reaction betwixt 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 advance reactions also 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-cardinal model, in which the substrate fits precisely into the active site (Figure 2.24). 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 altered so that information technology more closely resembles that of the transition state. The stress produced by such baloney of the substrate tin further facilitate its conversion to the transition state by weakening disquisitional bonds. Moreover, the transition state 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 agile site of the enzyme. (B) In the induced-fit model, substrate binding distorts the conformations of both substrate and enzyme. This distortion (more...)

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 procedure. In such cases, specific amino acid side chains in the agile site may react with the substrate and course bonds with reaction intermediates. The acidic and basic amino acids are often involved in these catalytic mechanisms, as illustrated in the post-obit discussion of chymotrypsin as an example of enzymatic catalysis.

Chymotrypsin is a fellow 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 cleave peptide bonds side by side to unlike amino acids. For example, whereas chymotrypsin digests bonds adjacent to hydrophobic amino acids, such as tryptophan and phenylalanine, trypsin digests bonds adjacent to basic amino acids, such every bit lysine and arginine. All the serine proteases, however, are similar in construction and use the same mechanism of catalysis. The agile sites of these enzymes contain three critical amino acids—serine, histidine, and aspartate—that drive hydrolysis of the peptide bond. Indeed, these enzymes are called serine proteases because of the central role of the serine residual.

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. For example, the binding pocket of chymotrypsin contains hydrophobic amino acids that interact with the hydrophobic side chains of its preferred substrates. In contrast, the binding pocket of trypsin contains a negatively charged acidic amino acid (aspartate), which is able to course an ionic bond with the lysine or arginine residues of its substrates.

Figure 2.25

Substrate binding by serine proteases. The amino acid adjacent 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 bounden pocket of trypsin contains (more...)

Substrate binding positions the peptide bail to exist cleaved side by side to the agile site serine (Figure 2.26). The proton of this serine is and 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 remainder. The serine reacts with the substrate, forming a tetrahedral transition state. The peptide bond is and then broken, and the C-concluding portion of the substrate is released from the enzyme. However, the North-concluding peptide remains bound to serine. This state of affairs is resolved when a water molecule (the second substrate) enters the active site and reverses the preceding reactions. The proton of the h2o molecule is transferred to histidine, and its hydroxyl group is transferred to the peptide, forming a second tetrahedral transition land. The proton is and then transferred from histidine back to serine, and the peptide is released from the enzyme, completing the reaction.

Figure ii.26

Catalytic mechanism of chymotrypsin. 3 amino acids at the active site (Ser-195, His-57, and Asp-102) play critical roles in catalysis.

This case 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 state. Although the thousands of enzymes in cells catalyze many dissimilar types of chemical reactions, the same basic principles apply to their functioning.

Coenzymes

In improver to binding their substrates, the agile sites of many enzymes bind other small molecules that participate in catalysis. Prosthetic groups are minor molecules leap to proteins in which they play disquisitional functional roles. For example, the oxygen carried by myoglobin and hemoglobin is spring to heme, a prosthetic group of these proteins. In many cases metallic ions (such every bit zinc or atomic number 26) are bound to enzymes and play central roles in the catalytic procedure. In addition, various depression-molecular-weight organic molecules participate in specific types of enzymatic reactions. These molecules are called coenzymes considering they work together with enzymes to enhance reaction rates. In contrast to substrates, coenzymes are non irreversibly contradistinct past the reactions in which they are involved. Rather, they are recycled and can participate in multiple enzymatic reactions.

Coenzymes serve every bit 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 (due east^-) from ane substrate, forming NADH. NADH can then donate these electrons to a second substrate, re-forming NAD⁺. Thus, NAD⁺ transfers electrons from the first substrate (which becomes oxidized) to the second (which becomes reduced).

Effigy ii.27

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

Several other coenzymes also act as electron carriers, and still others are involved in the transfer of a diversity of additional chemical groups (eastward.chiliad., carboxyl groups and acyl groups; Table 2.1). The same coenzymes role together with a variety of different enzymes to catalyze the transfer of specific chemic 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 non required by bacteria such equally Due east. coli but 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 of import feature of most enzymes is that their activities are not constant just instead can be modulated. That is, the activities of enzymes can be regulated and then that they function appropriately to see the varied physiological needs that may arise during the life of the 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 instance, the amino acid isoleucine is synthesized by a serial of reactions starting from the amino acid threonine (Figure 2.28). The get-go step in the pathway is catalyzed by the enzyme threonine deaminase, which is inhibited by isoleucine, the cease product of the pathway. Thus, an acceptable corporeality of isoleucine in the 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 so regulating the action of threonine deaminase, the 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 get-go stride in the conversion of threonine to iso-leucine is catalyzed by the enzyme threonine deaminase. The activity of this enzyme is inhibited by isoleucine, the end product of the pathway.

Feedback inhibition is one example of allosteric regulation, in which enzyme activity is controlled by the binding of minor molecules to regulatory sites on the enzyme (Effigy 2.29). The term "allosteric regulation" derives from the fact that the regulatory molecules bind non to the catalytic site, simply to a distinct site on the protein (allo= "other" and steric= "site"). Binding of the regulatory molecule changes the conformation of the poly peptide, which in plough alters the shape of the active site and the catalytic activity of the enzyme. In the case of threonine deaminase, bounden of the regulatory molecule (isoleucine) inhibits enzymatic activity. In other cases regulatory molecules serve as activators, stimulating rather than inhibiting their target enzymes.

Figure 2.29

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

The activities of enzymes can also exist regulated by their interactions with other proteins and by covalent modifications, such as the add-on of phosphate groups to serine, threonine, or tyrosine residues. Phosphorylation is a particularly common mechanism for regulating enzyme activity; the addition of phosphate groups either stimulates or inhibits the activities of many dissimilar enzymes (Figure 2.thirty). For example, muscle cells reply to epinephrine (adrenaline) by 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 role in controlling not only metabolic reactions merely also many other cellular functions, including cell growth and differentiation.

Effigy two.thirty

Protein phosphorylation. Some enzymes are regulated by 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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