Chapter 12

Question 1

a reaction of overall stoichiometry A –> P where A represents reactants and P represents products, may actually occur through a sequence …. (simple molecular processes)

Answer 1

elementary rxns

Question 2

descriptions of each elementary reaction collectively constitute the … description of the overall rxn process

Answer 2

mechanistic

Question 3

at constant temp, the rate of an elementary rxn is proportional to the frequency with which the reacting molecules. the proportionality constant is known as a … and is symbolized k

Answer 3

come together; rate constant

Question 4

for the elementary rxn A –> P the instantaneous rate of appearance/disappearance of reactant, which is called the … of the rxn, is v = k[A]

Answer 4

velocity

Question 5

the … of an elementary rxn corresponds to the … of the rxn, which is the number of molecules that must simultaneously collide to generate a product

Answer 5

reaction order; molecularity

Question 6

a first order elementary rxn is a … rxn

Answer 6

unimolecular

Question 7

… rxn is a second order rxn with an instaneous velocity v = k[A]^2

Answer 7

bimolecular

Question 8

… rxns are unusual bc of the simultaneous collision of three molecules is a rare event

Answer 8

termolecular

Question 9

the time for half of the reactant initially present to decompose, its … or …, t1/2, is a constant and hence independent of the initial concentration of the reactant

Answer 9

half-time; half-life

Question 10

the half time for a second order rxn is expressed … and therefore, in contrast to a first order rxn, depends on the …

Answer 10

t1/2 = 1/k[A]0; initial reactant []

Question 11

… rxn: when the concentration of one reactant relative to another in a bimolecular rxn is so large that the concentration of the other is not substantial

Answer 11

pseudo-first-order rxn

Question 12

all enzymes can be analyzed such that their rxn rates as well as their overall efficiency can be …

Answer 12

quantified

Question 13

E + S –> ES –> P + E
according to this model, when the substrate concentration becomes high enough to entirely convert the enzyme to the ES form, the second step of the rxn becomes the … and the overall reaction rate becomes insensitive to further increases in …

Answer 13

rate limiting; substrate []

Question 14

the michaelis-menten equation describes the rate of the enzymatic rxn as a function of …

Answer 14

substrate []

Question 15

(michaelis-menten assumptions) …–> menten and michaelist assumed that k-1&raquo_space; k2, so that the first step of the rxn reaches equilibrium

….: with the exception of the initial stage of the rxn [ES] remains approximately constant until the substrate is nearly exhausted. in other words, it maintains a … and can be treated as having a constant value

Answer 15

assumption of equilibrium assumption of steady state

Question 16

a reaction that achieves a steady state is not … –> [S] and [P[ are rapidly changing throughout the interval that [ES] is essentially constant

Answer 16

at equilibrium

Question 17

the michaelis constant, Km, is defined as:

Answer 17

(k-1 + k2)/k1

Question 18

expression for the initial velocity of the rxn (velocity at t = 0)
v0 =

Answer 18

(Vmax * [S])/ (KM + [S])

Question 19

the maximal velocity of a rxn, Vmax, occurs at high substrate concentrations, when the enzyme is …, that is, when it is entirely in the ES form

Answer 19

saturated

Question 20

Vmax =

Answer 20

k2 * [E]T

Question 21

KM is the substrate concentration at which the rxn velocity is …

Answer 21

half-maximal

Question 22

if an enzyme has a small value of Km, it achieves maximal catalytic efficiency at … substrate concentrations

Answer 22

low

Question 23

Since Ks is the dissociation constant of the Michaelis complex, as Ks decreases, the enzyme’s affinity for substrate …

Answer 23

increases

Question 24

we can define the catalytic constant, kcat, of an enzyme as:
Kcat = …

Answer 24

Vmax/[E]t

Question 25

kcat is known as the ... of an enzyme because it is the number of reaction processes (turnovers) that each active site catalyzes per unit time.

Answer 25

turnover number

Question 26

the quantity ... is a measure of an enzyme's catalytic efficiency

Answer 26

kcat/Km

Question 27

there is an upper limit to the value of kcat/Km; it can be no greater than ...; that is the decomposition of ES to E + P can occur no more frequently than E and S come together to form ES. The most efficient enzymes have kcat/Km values near the ... of 10^8 to 10^9 M^-1*s^-1

Answer 27

k1; diffusion-controlled limit

Question 28

a better method for determining the values of Vmax and Km uses the reciprocal of the Michaelis-Menten equation --> ... or ... plot

Answer 28

Lineweaver-Burk; double-reciprocal plot

Question 29

slope of Lineweaver burk is ..., the 1/v0 intercept is ..., and the extrapolated 1/[S] intercept is ..

Answer 29

Km/Vmax; 1/Vmax; -1/Km

Question 30

the steady state kinetic analysis of a rxn cannot unambiguously establish its

Answer 30

mechanism

Question 31

If kinetic data are not compatible with a given mechanism, then that mechanism must be ...

Answer 31

rejected

Question 32

Reactions in which all substrates must combine with the enzyme before a reaction can occur and products be released are known as ...

Answer 32

sequential reactions

Question 33

sequential reactions can be subclassified into those with a compulsory order of substrate addition to the enzyme, which are said to have an ... mechanism, and those with no preference for the order of substrate addition, which are described as having a ... mechanism

Answer 33

ordered; random

Question 34

Group-transfer reactions in which one or more products are released before all substrates have been added are known as ...

Answer 34

Ping Pong reactions.

Question 35

note that in ping pong rxns, the substrates A and B do not ... one another on the ... of the enzyme

Answer 35

encounter; surface

Question 36

substances that reduce an enzyme's activity by combining with it in a way that influences the binding of substrate and/or its turnover number are ...

Answer 36

inhibitors

Question 37

irreversible enzyme inhibitors, or ..., bind to the enzyme so tightly that they permanently block the enzyme's activity

Answer 37

inactivators

Question 38

reversible enzyme inhibitors diminish an enzyme's activity by interacting .. with it

Answer 38

reversibly

Question 39

a substance that competes directly with a normal substrate for an enzyme's substrate-binding site is known as a ...

Answer 39

competitive inhibitor

Question 40

competitive inhibitors usually resemble the ... so that it specifically binds to the active site but differs from the substrate so that it cannot react as the substrate does.

Answer 40

substrate

Question 41

...: in this phenomenon, a product of the rxn, which necessarily is able to bind to the enzyme's active site, may accumulate and compete with substrate for binding to the enzyme in subsequent catalytic cycles. this is one way in which the cell controls the activities of its enzymes

Answer 41

product inhibition

Question 42

...: Ki, the dissociation constant for enzyme-inhibitor binding)

Answer 42

inhibition constant

Question 43

... are particularly effective inhibitors.

Answer 43

transition state analogs

Question 44

several of the drugs used to block ..., an essential enzyme for production of the human immunodeficiency virus, are compounds that were designed to mimic the enzyme's transition state and bind to the enzyme with high affinity

Answer 44

HIV protease

Question 45

a competitive inhibitor reduces the concentration of ... available for substrate binding

Answer 45

free enzyme

Question 46

michaelis-menten for when an inhibitor is present: | v0 =

Answer 46

(Vmax*[S])/(a*Km + [S])

Question 47

a in michaelis-menten is:

Answer 47

a = 1 + [I]/Ki

Question 48

... = a*Km, which is the apparent Km, that is, the Km value that would be measured in the absence of the knowledge that inhibitor is present

Answer 48

app | Km

Question 49

a is the factor by which ... in order to overcome the effect of the presence of inhibitor

Answer 49

[S] must be increased

Question 50

as [S] approaches infinity, v0 approaches ... for any concentration of inhibitor. the inhibitor does not affect the enzyme's turnover number

Answer 50

Vmax

Question 51

competitive inhibition is the principle behind the use of ... to treat methanol poisoning

Answer 51

ethanol

Question 52

in ..., the inhibitor bind directly to the enzyme substrate complex but not to the free enzyme

Answer 52

uncompetitive inhibition

Question 53

the binding of uncompetitive inhibitor, which need not resemble substrate, presumably ..., thereby rendering the enzyme catalytically inactive

Answer 53

distorts the active site

Question 54

uncompetitive inhibition requires that the inhibitor affect the ... function of the enzyme but not its ...

Answer 54

catalytic; substrate binding

Question 55

uncompetitive inhibition is significant only for ... enzymes

Answer 55

multisubstrate

Question 56

...: many reversible inhibitors interact with the enzyme in a way that affects substrate binding as well as catalytic activity

Answer 56

mixed inhibition/noncompetitive inhibition

Question 57

a mixed inhibitor binds to enzyme sites that participate in both .. and ..

Answer 57

substrate binding; catalysis

Question 58

as in uncompetitive inhibition, the apparent values of ... and ... are modulated by the presence of inhibitor

Answer 58

Km and Vmax

Question 59

if the enzyme and enzyme substrate complex bind the inhibitor with equal affinity, then Km apparent is unchanged from the Km for the rxn in the absence of inhibitor. in this case, only Vmax is affected, a phenomenon that is named ...

Answer 59

pure noncompetitive inhibition

Question 60

the kinetics of an enzyme inactivator (an irreversible inhibitor) resembles that of a ... bc the inactivator reduces the concentration of functional enzyme at all substrate concentrations

Answer 60

pure noncompetitive inhibitor

Question 61

Double-reciprocal plots for mixed inhibition consist of lines that have the slope ..., a 1/νo intercept of ..., and a 1/[S] intercept of... (Fig. 12-10).

Answer 61

αKM/Vmax; α′/Vmax; −α′/αKM

Question 62

The lines for increasing values of [I] (representing increasing saturation of E and ES with I) intersect to the left of the ... axis. For pure noncompetitive inhibition, the lines intersect on the 1/[S] axis at .... As with uncompetitive inhibition, substrate binding does not reverse the effects of mixed inhibition.

Answer 62

1/νo; −1/KM

Question 63

two ways control of catalytic activities may occur: control of enzyme ...: the amount of a given enzyme in a cell depends on both its ... and its... each of these rates is directly controlled by the cell and is subject to dramatic changes over time spans of minutes (in bacteria) to hours (in higher organisms).

Answer 63

availability; rate of synthesis; rate of degradation;

Question 64

two ways control of catalytic activities may occur: control of enzyme ...; can be inhibited/modulated an enzyme's substrate-binding affinity may vary with the binding of small molecules, called ... these mechanisms can cause large changes in enzymatic activity

Answer 64

activity; allosteric effectors

Question 65

the activities of many enzymes are controlled by ..., usually phosphorylation and dephosphorylation of specific Ser, Thr, or Tyr residues

Answer 65

covalent modification

Question 66

aspartate transcarbamoylase from E. coli catalyzes the formation of ... from ... and ..

Answer 66

N-carbamoyl aspartate; carbamoyl phosphate; aspartate

Question 67

...: inhibits an earlier step in its own biosynthesis

Answer 67

feedback inhibitor

Question 68

for ATcase, the regulatory subunits allosterically reduce the activity of the ... in in the intact enzyme

Answer 68

catalytic subunits

Question 69

for ATCase, the binding of substrate to one catalytic subunit increases the ... and ... of the other five catalytic subunits and accounts for the enzyme's cooperative substrate binding

Answer 69

substrate-binding affinity; catalytic activity

Question 70

the activity of ATCase is increased by ... and decreased by ..., which alter the conformation of the catalytic sites by stabilizing the R and the T states of the enzyme, respectively

Answer 70

ATP; CTP

Question 71

the enzymatic activity of glycogen phosphorylase is controlled by its ../... as well as by the influence of ...

Answer 71

phosphorylation; dephosphorylation; allosteric effectors

Question 72

phosphorylation/dephosphorylation modification/demodification processes are catalyzed by enzymes known as ... and ...

Answer 72

protein kinases; protein phosphatases

Question 73

glycogen phosphorylase catalyzes the ... (bond cleavage by the substitution of a phosphate group) of glycogen to yield glucose-1-phosphate (G1P)

Answer 73

phosphorolysis

Question 74

mammals express three ... (catalytically and structurally similar but genetically distinct enzymes from the same organism; also called ...) of glycogen phosphorylase, those from muscle, brain and liver

Answer 74

isozymes; isoforms

Question 75

glycogen phosphorylase has two conformational states, the enzymatically active ... state and the enzymatically inactive .. state. the inactive state is so bc of the fact that it has a malformed active site and a surface loop that blocks substrate access to its binding site

Answer 75

R; T

Question 76

the phosphorylation of ... promotes phosphorylase's T --> R conformational change

Answer 76

Ser 14

Question 77

... and ... (to which the G1P product of the glycogen phosphorylase rxn is converted preferentially bind to the T state of phophorylase b and inactivate the enzyme whereas ...preferentially binds to the r state of phosphorylase b and activates it

Answer 77

ATP; glucose-6-phosphate (G6P); AMP

Question 78

the Ser 14 phosphate group of glycogen phosphorylase functions as a sort of internal ... that shifts the enzymes T R equilibrium in favor of the ...state

Answer 78

allosteric effector; R

Question 79

the enzymes that catalyze the phosphorylation and dephosphorylation of glycogen phosphorylase are ... and ...

Answer 79

phosphorylase kinase; phosphoprotein phosphatase

Question 80

a drug candidate that exhibits a desired effect is called a ... a good one binds to its target protein with a dissociation constant of less than 1 micromolar

Answer 80

lead compound

Question 81

a lead compound is used as a point of ... to design more efficacious compounds

Answer 81

departure

Question 82

besides causing the desired response in its isolated target protein, a useful drug must be delivered in sufficiently ... to this protein where it resides in the human body

Answer 82

high concentration

Question 83

the most effective drugs are usually a compromise; they are neither too ... nor too ..

Answer 83

lipophilic; hydrophilic

Question 84

differences in rxns to drugs arise from ... among individuals as well as differences in their ..., other drugs they are taking, age, sex, and environmental factors

Answer 84

genetic differences; disease states

Question 85

drug-drug interactions are often mediated by ...

Answer 85

cytochromes P450

Question 86

an ... can be developed for use as a drug through structure-based and/or combinatorial methods. it must then be tested for safety and efficacy in clinical trials

Answer 86

enzyme inhibitor