Chapter 12 Flashcards
a reaction of overall stoichiometry A –> P where A represents reactants and P represents products, may actually occur through a sequence …. (simple molecular processes)
elementary rxns
descriptions of each elementary reaction collectively constitute the … description of the overall rxn process
mechanistic
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
come together; rate constant
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]
velocity
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
reaction order; molecularity
a first order elementary rxn is a … rxn
unimolecular
… rxn is a second order rxn with an instaneous velocity v = k[A]^2
bimolecular
… rxns are unusual bc of the simultaneous collision of three molecules is a rare event
termolecular
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
half-time; half-life
the half time for a second order rxn is expressed … and therefore, in contrast to a first order rxn, depends on the …
t1/2 = 1/k[A]0; initial reactant []
… 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
pseudo-first-order rxn
all enzymes can be analyzed such that their rxn rates as well as their overall efficiency can be …
quantified
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 …
rate limiting; substrate []
the michaelis-menten equation describes the rate of the enzymatic rxn as a function of …
substrate []
(michaelis-menten assumptions) …–> menten and michaelist assumed that k-1»_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
assumption of equilibrium assumption of steady state
a reaction that achieves a steady state is not … –> [S] and [P[ are rapidly changing throughout the interval that [ES] is essentially constant
at equilibrium
the michaelis constant, Km, is defined as:
(k-1 + k2)/k1
expression for the initial velocity of the rxn (velocity at t = 0)
v0 =
(Vmax * [S])/ (KM + [S])
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
saturated
Vmax =
k2 * [E]T
KM is the substrate concentration at which the rxn velocity is …
half-maximal
if an enzyme has a small value of Km, it achieves maximal catalytic efficiency at … substrate concentrations
low
Since Ks is the dissociation constant of the Michaelis complex, as Ks decreases, the enzyme’s affinity for substrate …
increases
we can define the catalytic constant, kcat, of an enzyme as:
Kcat = …
Vmax/[E]t
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.
turnover number
the quantity … is a measure of an enzyme’s catalytic efficiency
kcat/Km
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
k1; diffusion-controlled limit
a better method for determining the values of Vmax and Km uses the reciprocal of the Michaelis-Menten equation –> … or … plot
Lineweaver-Burk; double-reciprocal plot
slope of Lineweaver burk is …, the 1/v0 intercept is …, and the extrapolated 1/[S] intercept is ..
Km/Vmax; 1/Vmax; -1/Km
the steady state kinetic analysis of a rxn cannot unambiguously establish its
mechanism
If kinetic data are not compatible with a given mechanism, then that mechanism must be …
rejected
Reactions in which all substrates must combine with the enzyme before a reaction can occur and products be released are known as …
sequential reactions
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
ordered; random
Group-transfer reactions in which one or more products are released before all substrates have been added are known as …
Ping Pong reactions.
note that in ping pong rxns, the substrates A and B do not … one another on the … of the enzyme
encounter; surface
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 …
inhibitors
irreversible enzyme inhibitors, or …, bind to the enzyme so tightly that they permanently block the enzyme’s activity
inactivators
reversible enzyme inhibitors diminish an enzyme’s activity by interacting .. with it
reversibly
a substance that competes directly with a normal substrate for an enzyme’s substrate-binding site is known as a …
competitive inhibitor
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.
substrate
…: 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
product inhibition
…: Ki, the dissociation constant for enzyme-inhibitor binding)
inhibition constant
… are particularly effective inhibitors.
transition state analogs
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
HIV protease
a competitive inhibitor reduces the concentration of … available for substrate binding
free enzyme
michaelis-menten for when an inhibitor is present:
v0 =
(Vmax[S])/(aKm + [S])
a in michaelis-menten is:
a = 1 + [I]/Ki
… = 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
app
Km
a is the factor by which … in order to overcome the effect of the presence of inhibitor
[S] must be increased
as [S] approaches infinity, v0 approaches … for any concentration of inhibitor. the inhibitor does not affect the enzyme’s turnover number
Vmax
competitive inhibition is the principle behind the use of … to treat methanol poisoning
ethanol
in …, the inhibitor bind directly to the enzyme substrate complex but not to the free enzyme
uncompetitive inhibition
the binding of uncompetitive inhibitor, which need not resemble substrate, presumably …, thereby rendering the enzyme catalytically inactive
distorts the active site
uncompetitive inhibition requires that the inhibitor affect the … function of the enzyme but not its …
catalytic; substrate binding
uncompetitive inhibition is significant only for … enzymes
multisubstrate
…: many reversible inhibitors interact with the enzyme in a way that affects substrate binding as well as catalytic activity
mixed inhibition/noncompetitive inhibition
a mixed inhibitor binds to enzyme sites that participate in both .. and ..
substrate binding; catalysis
as in uncompetitive inhibition, the apparent values of … and … are modulated by the presence of inhibitor
Km and Vmax
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 …
pure noncompetitive inhibition
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
pure noncompetitive inhibitor
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).
αKM/Vmax; α′/Vmax; −α′/αKM
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.
1/νo; −1/KM
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).
availability; rate of synthesis; rate of degradation;
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
activity; allosteric effectors
the activities of many enzymes are controlled by …, usually phosphorylation and dephosphorylation of specific Ser, Thr, or Tyr residues
covalent modification
aspartate transcarbamoylase from E. coli catalyzes the formation of … from … and ..
N-carbamoyl aspartate; carbamoyl phosphate; aspartate
…: inhibits an earlier step in its own biosynthesis
feedback inhibitor
for ATcase, the regulatory subunits allosterically reduce the activity of the … in in the intact enzyme
catalytic subunits
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
substrate-binding affinity; catalytic activity
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
ATP; CTP
the enzymatic activity of glycogen phosphorylase is controlled by its ../… as well as by the influence of …
phosphorylation; dephosphorylation; allosteric effectors
phosphorylation/dephosphorylation modification/demodification processes are catalyzed by enzymes known as … and …
protein kinases; protein phosphatases
glycogen phosphorylase catalyzes the … (bond cleavage by the substitution of a phosphate group) of glycogen to yield glucose-1-phosphate (G1P)
phosphorolysis
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
isozymes; isoforms
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
R; T
the phosphorylation of … promotes phosphorylase’s T –> R conformational change
Ser 14
… 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
ATP; glucose-6-phosphate (G6P); AMP
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
allosteric effector; R
the enzymes that catalyze the phosphorylation and dephosphorylation of glycogen phosphorylase are … and …
phosphorylase kinase; phosphoprotein phosphatase
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
lead compound
a lead compound is used as a point of … to design more efficacious compounds
departure
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
high concentration
the most effective drugs are usually a compromise; they are neither too … nor too ..
lipophilic; hydrophilic
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
genetic differences; disease states
drug-drug interactions are often mediated by …
cytochromes P450
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
enzyme inhibitor
