Chapter 12 Wiley
Define terms: 1. Aspartate transcarbamoylase (ATCase) 2. Carbamoylphosphate + Aspartate 3. N-carbamoyl aspartate + H2PO4- 4. ATP 5. Cytidine triphosphate CTP
1. Aspartate transcarbamoylase (ATCase): ALLOSTERIC ACTIVATOR 2. Carbamoylphosphate + Aspartate: REACTANTS 3. N-carbamoyl aspartate + H2PO4-: PRODUCTS 4. ATP: ALLOSTERIC ACTIVATOR 5. Cytidine triphosphate CTP: CYTIDINE TRIPHOSPHATE CTP
Terminology definition: 1. Michaelis complex 2. Michaelis constant, Km 3. Initial velocity 4. Maximal velocity 5. Catalytic constant
1. Michaelis complex: the enzyme-substrate complex, ES 2. Michaelis constant, Km: the concentration of substrate at which the velocity is half-maximal 3. Initial velocity: the velocity at t=0 4. Maximal velocity: the velocity when the enzyme is saturated with substrate 5. Catalytic constant: also known as the turnover number
Match terminology: 1. competitive inhibitor 2. uncompetitive inhibitor 3. mixed inhibitor 4. inactivator
1. competitive inhibitor: Increases K_M 2. uncompetitive inhibitor: Decreases K_M and V_max 3. mixed inhibitor: Decreases V_max, while K_M may increase or decrease 4. inactivator: Decreases [E]_T
A ... inhibitor binds only to the free enzyme, not to the enzyme-substrate complex.
A COMPETITVE inhibitor binds only to the free enzyme, not to the enzyme-substrate complex.
A common type of covalent modification of regulatory enzymes involves ______ of serine residues.
A common type of covalent modification of regulatory enzymes involves PHOSPHORYLATION of serine residues.
A compound that distorts the active site, rendering the enzyme catalytically inactive is called ...
A compound that distorts the active site, rendering the enzyme catalytically inactive is called A UNCOMPETITIVE INHIBITOR.
A lead compound for a new drug should bind to its target protein with a very ______.
A lead compound for a new drug should bind to its target protein with a very SMALL Ks .
A rate ... describes the progress of a reaction as a function of time.
A rate EQUATION describes the progress of a reaction as a function of time.
A two-substrate enzymatic reaction in which one product is produced before the second substrate binds to the enzyme has a ______ mechanism.
A two-substrate enzymatic reaction in which one product is produced before the second substrate binds to the enzyme has a PING PONG mechanism.
Parallel lines on a Lineweaver-Burk plot indicate... A. uncompetitive inhibition. B. decrease in Vmax. C. an increase in KM. D. decrease in KM.
A, B, AND D A. uncompetitive inhibition. B. decrease in Vmax. D. decrease in KM.
Enzyme activity in cells is controlled by which of the following? A. covalent modifications B. allosteric effectors C. modulation of expression levels D. feedback inhibition
A, B, C, & D A. covalent modifications B. allosteric effectors C. modulation of expression levels D. feedback inhibition
KM A. is the concentration of substrate where the enzyme achieves ½Vmax. B. is equal to Ks. C. measures the stability of the product D. is high if the enzyme has high affinity for the substrate. E. All of the above are correct.
A. is the concentration of substrate where the enzyme achieves ½Vmax.
Irreversible enzyme inhibitors ... A. inactivate the enzyme. B. inhibit competitively. C. maximize product by minimizing ES E+S. D. behave allosterically. E. function via Ping Pong mechanism.
A. inactivate the enzyme.
An enzyme's substrate-binding affinity may vary with the binding of small molecules called ...
An enzyme's substrate-binding affinity may vary with the binding of small molecules called ALLOSTERIC EFFECTORS.
Assume a first order reaction, the rate of the reaction 2A ---> B is dependent on ______.
Assume a first order reaction, the rate of the reaction 2A ---> B is dependent on [A].
Which of the following groups of isotopes includes only radioactive isotopes that are commonly used in biochemical experiments? A. 3H, 12C, 32P, 35S B. 3H, 14C, 32P, 35S C. 2H, 14C, 32P, 35S D. 3H, 14C, 31P, 35S
B. 3H, 14C, 32P, 35S
I propose to design a new drug which will act as an inhibitor for an enzyme. If I have used all current information about the mechanism of this enzyme to design this inhibitor and I carefully engineer it with similar chemical properties of the transition state, what type of inhibitor am I attempting to engineer and how will I know if I have succeeded? A. A competitive inhibitor, collect kinetic data both in the presence and absence of inhibitor and watch for a change in Vmax. B. A competitive inhibitor, collect kinetic data both in the presence and absence of inhibitor and watch for a change in KM. C. A uncompetitive inhibitor, collect kinetic data both in the presence and absence of inhibitor and watch for a change in KM. D. A uncompetitive inhibitor, collect kinetic data both in the presence and absence of inhibitor and watch for a change in Vmax.
B. A competitive inhibitor, collect kinetic data both in the presence and absence of inhibitor and watch for a change in KM.
Which expression containing the free energy of activation (∆G‡) is proportional to the rate of a reaction? A. ln(∆G‡ /RT) B. e(-∆G‡ /RT) C. -∆G‡ /RT D. +∆G‡ /RT
B. e^(-∆G‡ /RT)
At substrate concentrations much lower than the enzyme concentration, the rate of reaction is expected to be inversely proportional to substrate concentration. A. the rate of reaction is expected to be directly proportional to substrate concentration. B. first order enzyme kinetics are not observed. C. the KM is lower. D. the rate of reaction is independent of substrate concentration.
B. first order enzyme kinetics are not observed.
... reactions are enzyme reactions with two substrates.
BISUBSTRATE reactions are enzyme reactions with two substrates.
A Lineweaver-Burk plot is also referred to as ... A. a sigmoidal plot. B. a Michaelis-Menten plot. C. a linear plot. D. a double reciprocal plot.
C AND D C. a linear plot. D. a double reciprocal plot.
Allosteric activators ... A. bind via covalent attachment. B. stabilize conformations with higher Ks. C. stabilize conformations with higher substrate affinity. D. All of the above.
C. stabilize conformations with higher substrate affinity.
Protein kinases are involved in ... A. the digestion of drugs to potentially toxic byproducts. B. the degradation of enzymes to the component amino acids. C. the phosphorylation of a wide variety of proteins. D. the metabolism of drugs to water soluble, excretable compounds.
C. the phosphorylation of a wide variety of proteins.
If ATP is a substrate for an enzyme, and ADP was found to be a more potent competitive inhibitor than adenosine for the reaction, which of the following would be a plausible explanation? A. The ribose ring must be important for binding. B. Adenosine is too large to bind at the active site. C. Adenosine must be binding outside of the active site. D. The phosphate groups of ADP must be important for binding.
D. The phosphate groups of ADP must be important for binding.
The KM can be considered to be the same as the dissociation constant KS for E + S binding if... A. the concentration of [ES] is unchanged. B. ES E + P is fast compared to ES E + S. C. k1 >> k2. D. k2 << k-1. E. this statement cannot be completed because KM can never approximate KS.
D. k2 << k-1.
KM is ... A. a measure of the catalytic efficiency of the enzyme. B. equal to half of Vmax. C. the rate constant for the reaction ES E + P. D. the [S] that half-saturates the enzyme. E. a ratio of substrate concentration relative to catalytic power.
D. the [S] that half-saturates the enzyme.
Different enzymes that catalyze the same reaction, although may be found in different tissues, are known as ______.
Different enzymes that catalyze the same reaction, although may be found in different tissues, are known as ISOZYMES.
An extremely efficient enzyme called "efficase" catalyzes the conversion of "A" to "B." A researcher decides to mutate the enzyme in order to try to improve its performance. Following active site mutations, a significant reduction in the value of KM and Vmax was observed. Which of the following may have occurred? A. The affinity of the enzyme for the substrate was increased to a point which did not favor propagation (continuation) of the reaction. B. The decrease in Vmax was not related to the decrease in KM. C. If the reaction was first-order, the change in KM cannot have affected Vmax. D. The stability of E+S (E+A as written above) was increased, thereby increasing the KM. E. The reverse reaction (breakdown of EA to E+A) was favored, slowing the Vmax.
E. The reverse reaction (breakdown of EA to E+A) was favored, slowing the Vmax.
E. coli aspartate transcarbamoylase has 6 catalytic subunits and ... regulatory subunits.
E. coli aspartate transcarbamoylase has 6 catalytic subunits and 6 regulatory subunits.
Noncovalent modifications of an enzyme cannot significantly influence its activity. T/F
FALSE Noncovalent allosteric effectors typically influence the activity of enzymes significantly.
All inhibitors must resemble the substrate in some way. T/F
FALSE Only competitive inhibitors must resemble the substrate.
Steady state kinetic analysis is commonly used to establish reaction mechanisms. T/F
FALSE Steady state kinetic analysis cannot establish reaction mechanisms.
The reaction order of an elementary reaction corresponds to the number of different types of molecules that must simultaneously collide to generate a product. T/F
FALSE The reaction order of an elementary reaction corresponds to the actual number of molecules of any type that must simultaneously collide to generate a product.
Structural differences between the T-state and the R-state of ATCase are hard to discern. T/F
FALSE The structural differences are easy to see.
The double-reciprocal plots for irreversible inhibition resemble those for competitive inhibition.
FALSE They resemble those for mixed inhibition, where K_I = K'_I.
For a reaction A + B ----> C, if the concentration of B is much larger than A so that [B] remains constant during the reaction while [A] is varied, the kinetics will be ....
For a reaction A + B ----> C, if the concentration of B is much larger than A so that [B] remains constant during the reaction while [A] is varied, the kinetics will be PSEUDO-FIRST-ORDER.
If A ---> B is a zero-order reaction, the rate is dependent on ______.
If A ---> B is a zero-order reaction, the rate is dependent on THE RATE CONSTANT.
In ______, the inhibitor binds to a site involved in both substrate binding and catalysis.
In COMPETITIVE INHIBITION, the inhibitor binds to a site involved in both substrate binding and catalysis.
In ... inhibition, the inhibitor binds only to the enzyme-substrate complex, not to the free enzyme.
In UNCOMPETITIVE inhibition, the inhibitor binds only to the enzyme-substrate complex, not to the free enzyme.
In uncompetitive inhibition, the inhibitor binds only to the ______.
In uncompetitive inhibition, the inhibitor binds only to the ES COMPLEX.
It .... necessary to know [E]T in order to determine Km. The variables required to determine KM are ... and ....
It IS NOT necessary to know [E]T in order to determine Km. The variables required to determine KM are [S] and Vo.
It .... necessary to know [E]T in order to determine Vmax. The variables required to determine Vmax are .... and ....
It IS NOT necessary to know [E]T in order to determine Vmax. The variables required to determine Vmax are [S] and Vo.
It ... necessary to know [E]T in order to determine kcat because kcat = ...
It IS necessary to know [E]T in order to determine kcat because kcat = V max/ [E] total.
It is usually easier to calculate an enzyme's reaction velocity from the rate of appearance of ... rather than the rate of disappearance of a .... Enzyme activity is measured as an ... reaction velocity, the velocity before much ... has been depleted and before much ... has been generated. It is easier to measure the appearance of a small amount of ... from a baseline of zero ... than to measure the disappearance of small amount of ... against a background of high concentration of ....
It is usually easier to calculate an enzyme's reaction velocity from the rate of appearance of PRODUCT rather than the rate of disappearance of a SUBSTRATE. Enzyme activity is measured as an INITIAL reaction velocity, the velocity before much SUBSTRATE has been depleted and before much PRODUCT has been generated. It is easier to measure the appearance of a small amount of PRODUCT from a baseline of zero PRODUCT than to measure the disappearance of small amount of SUBSTRATE against a background of high concentration of SUBSTRATE.
________ clinical trials are focused on evaluating the efficacy of new drug candidates, and usually use _____ test.
PHASE 2 clinical trials are focused on evaluating the efficacy of new drug candidates, and usually use SINGLE BLIND test.
Pyrimidine synthesis is regulated by feedback ... of aspartate transcarbamoylase.
Pyrimidine synthesis is regulated by feedback INHIBITION of aspartate transcarbamoylase.
Substances that reduce an enzyme's activity by reversibly combining with the enzyme are called ...
Substances that reduce an enzyme's activity by reversibly combining with the enzyme are called INHIBITORS.
A large part of the modern pharmaceutical arsenal consists of enzyme inhibitors. T/F
TRUE
All enzymes can be analyzed such that their reaction rates and their overall efficiencies can be quantitated. T/F
TRUE
Mixed inhibition is characterized by two dissociation constants for inhibitor binding. T/F
TRUE
The Michaelis-Menten equation describes a rectangular hyperbola. T/F
TRUE
The catalytic activity of an enzyme can be regulated by controlling the amount of the enzyme available and by structural alterations of the enzyme that influence substrate binding. T/F
TRUE
The rate of an elementary reaction is proportional to the frequency with which the reacting molecules come together. T/F
TRUE
The E+S ---> E+P reaction is ______.
The E+S ----> E+P reaction is bimolecular.
The Lineweaver-Burk plot is also known as the double-... plot.
The Lineweaver-Burk plot is also known as the double- RECIPROCAL plot.
The study of enzymatic reaction rates is called enzyme ...
The study of enzymatic reaction rates is called enzyme KINETICS.
The type of enzyme inhibition in which Vmax is unaffected is ______.
The type of enzyme inhibition in which Vmax is unaffected is COMPETITIVE INHIBITION.
When [S] = KM, ν0 = (_____)× (Vmax).
When [S] = KM, ν0 = (0.5)× (Vmax).
