chapter8

Question 1

A nucleophile

Answer 1

A nucleophile is a chemical that is attracted to regions of positive charge in another molecule. A nucleophile participates in a chemical reaction by donating electrons to another chemical, called the electrophile

Question 2

covalent catalysis

Answer 2

the active site contains a reactive group, usually a powerful nucleophile that becomes temporarily covalently modified in the course of catalysis.
Covalent catalysis relies on the formation of a covalent bond between the catalyst and substrate to lower the activation energy of the reaction. This type of catalysis involves a direct chemical modification of the substrate by the catalyst.

Question 3

General Acid–Base Catalysis

Answer 3

In general acid–base catalysis, a molecule other than water plays the role of a proton donor or acceptor.

Question 4

Metal Ion Catalysis (3)

Answer 4

Metal ions can function catalytically in several ways. For instance, a metal ion may serve as an electrophilic catalyst, stabilizing a negative charge on a reaction intermediate. Alternatively, a metal ion may generate a nucleophile by increasing the acidity of a nearby
molecule such as water. Finally, a metal ion may bind to the substrate, increasing the number of interactions with the enzyme and thus the binding energy. Metal ions are
required cofactors for many of the enzymes we will encounter in our study of biochemistry.

Question 5

Catalysis by Approximation and Orientation

Answer 5

Many reactions include two distinct substrates. In such cases, the reaction rate may be considerably enhanced by bringing the two substrates into proximity and in the proper orientation on a single binding surface of an enzyme.
Catalysis by approximation and orientation involves bringing reactant molecules into close proximity and correct orientation to enhance the likelihood of a reaction occurring. This type of catalysis is particularly relevant in enzyme-catalyzed reactions, where enzymes position substrates favorably for reaction.

Question 6

The full complement of binding interactions between an enzyme and a substrate is formed only when ——

Answer 6

the substrate is in the transition state

Question 7

The pH dependence of enzymes is due to the presence of —–

Answer 7

ionizable R groups

Question 8

reversible inhibition is characterized by …..

Answer 8

rapid dissociation of the enzyme–inhibitor complex

Question 9

There are three common types of reversible inhibition:

Answer 9

competitive inhibition, uncompetitive inhibition, and noncompetitive inhibition

Question 10

competitive inhibition (4)

inhibitor description+ what happens+ how to relieve+diminishes

Answer 10

• the inhibitor resembles the substrate and binds to the active site of the enzyme
• The substrate is thereby prevented from binding to the same active site.
• diminishing the proportion of enzyme molecules that are bound to substrate
• At any given inhibitor concentration, competitive inhibition can be relieved by increasing the substrate concentration. Under these conditions, the substrate “outcompetes” the inhibitor for the active site.

Question 11

Uncompetitive inhibition (2)

What it is+cannot be…

Answer 11

• The uncompetitive inhibitor’s binding site is created
  only when the enzyme binds the substrate (the inhibitor binds only to the enzyme–substrate complex)
• cannot be overcome by the addition of more substrate

Question 12

noncompetitive inhibition (2)

binding site+acts by…

Answer 12

• the inhibitor and substrate can bind simultaneously to an enzyme molecule at different binding sites
• A noncompetitive inhibitor acts by decreasing the overall number of active enzyme molecules

Question 13

Noncompetitive inhibition, in contrast with competitive inhibition, cannot be overcome by ….

Answer 13

increasing the substrate concentration

Question 14

In the presence of a competitive inhibitor, an enzyme will have the same —— as in the absence of an inhibitor. The effect of a competitive inhibitor is to increase the apparent value of —— meaning that more substrate is needed to obtain the same reaction rate.

Answer 14

• Vmax
• Km

Question 15

uncompetitive inhibition Vmax, [s] and Km

Answer 15

• In uncompetitive inhibition, the inhibitor binds only to the ES complex. This enzyme–substrate–inhibitor complex, ESI, does not proceed to form any product. Because some unproductive ESI complex will always be present, Vmax will be lower in the presence of an inhibitor than in its absence
• The uncompetitive inhibitor also lowers the apparent value of Km, because the inhibitor binds to ES to form ESI, depleting ES. A lower concentration of S is required to form half of the maximal concentration of ES, resulting in a reduction of the apparent value of Km

Question 16

In noncompetitive inhibition Vmax and Km

Answer 16

• a substrate can bind to the enzyme–inhibitor complex as well as to the enzyme alone. In either case, the enzyme inhibitor–substrate complex does not proceed to form product. The value of Vmax is decreased.
• the value of Km is unchanged

Question 17

Competitive inhibition illustrated on a double-reciprocal plot

Answer 17

Question 18

Uncompetitive inhibition illustrated on a double-reciprocal plot.

Answer 18

Question 19

Noncompetitive inhibition illustrated on a double-reciprocal plot

Answer 19

Question 20

irreversible inhibitor dissociates very —- from its target enzyme because it has become ——

Answer 20

• slowly
• tightly bound to the enzyme, either covalently or non-covalently

Question 21

least specific

Group-specific reagents (2)

+specific for…

Answer 21

• modify specific R groups of amino acids
• specific for a particular reactive R group, not specific for a particular enzyme

Question 22

Affinity labels, also called substrate analogs

Answer 22

• molecules that covalently modify active-site residues and are structurally similar to an enzyme’s substrate
• covalently bind to their target causing its inactivation
• Affinity labels are small molecules or compounds that possess structural similarities to a substrate of an enzyme or receptor. They are designed to bind tightly and specifically to the active site of the enzyme or receptor. The key characteristic of affinity labels is their ability to covalently modify the active site or nearby residues upon binding. This modification can disrupt the enzyme’s function or signaling activity, essentially “labeling” or altering the active site irreversibly. Affinity labels are often used in biochemical studies to probe enzyme-substrate interactions and mechanisms.

Question 23

most specific

Suicide inhibitors, or mechanism-based inhibitors

Answer 23

The inhibitor binds to the enzyme as a substrate and is initially processed by the normal catalytic mechanism. The mechanism of catalysis then generates a chemically reactive intermediate that inactivates the enzyme through covalent modification.

Question 24

transition state analog

Answer 24

A transition state analog, one exhibiting the same properties such as shape and charge of the original transition molecule, may come in and bind. Although the analog displays similar properties as the original transition molecule, but it has higher affinity for the enzyme than the natural substrate and will ultimately deactivate and inhibit the enzyme and prevent it from binding to a substrate.

Question 25

suicide vs affinity

Answer 25

Affinity influences the binding strength between molecules, affecting enzymatic activity or signaling. Suicide inhibition irreversibly modifies the enzyme's active site, disrupting its function permanently.

Question 26

Oxidoreductases

Answer 26

These enzymes transfer electrons between molecules. In other words, these enzymes catalyze oxidation–reduction reactions

Question 27

Transferases

Answer 27

These enzymes transfer functional groups between molecules

Question 28

Hydrolyases

Answer 28

A hydrolyase cleaves molecules by the addition of water.

Question 29

Lyases

Answer 29

A lyase adds atoms or functional groups to a double bond or removes them to form double bonds.

Question 30

Isomerases

Answer 30

These enzymes move functional groups within a molecule.

Question 31

Ligases

Answer 31

join two molecules in a reaction powered by ATP hydrolysi

Question 32

Translocases

Answer 32

Catalyze movement of ions or molecules across membranes or their seperation within membranes

Question 33

Protein breakdown is catalyzed by a large class of enzymes called ----- and they -----

Answer 33

- proteolytic enzymes or proteases. - cleave proteins by a hydrolysis reaction—the addition of a molecule of water to a peptide bond

Question 34

chymotrypsin, which is secreted by the pancreas in response to a ----

Answer 34

meal

Question 35

Chymotrypsin cleaves peptide bonds selectively on .....

Answer 35

the carboxyl-terminal side of the large hydrophobic amino acids such as tryptophan, tyrosine, phenylalanine, methionine, and isoleucine

Question 36

How does chymotrypsin use covalent modification?

Answer 36

The enzyme employs a powerful nucleophile to attack the unreactive carbonyl group of the substrate. This nucleophile becomes covalently attached to the substrate briefly in the course of catalysis.

Question 37

catalytic triad

Answer 37

The side chain of serine 195 is hydrogenbonded to the imidazole ring of histidine 57. The NH group of this imidazole ring is, in turn, hydrogen-bonded to the carboxylate group of aspartate 102

Question 38

The catalytic triad, shown on the below, converts serine 195 into a potent ----

Answer 38

nucleophile

Question 39

What is the purpose of the oxyanion hole in chymotrypsin?

Answer 39

to stabilise the tetrahedral intermediate anion formed during proteolysis and protects substrate's negatively charged oxygen from water molecules.