Chapter 12: Enzyme Kinetics, Inhibition and Control

Matching
A) B) C) D) E) F) G) H) I) J) K) L) M) isozymes substrate binding rate constant Ping Pong bimolecular ES complex large KD mixed inhibition unimolecular [A]2 competitive inhibition phosphorylation small KD

1. The 2AB reaction is ______. Ans: E Level of Difficulty: Easy Section: 12.1.A Learning objective: Reaction Kinetics 2. The rate of the reaction 2AB is dependent on ______. Ans: J Level of Difficulty: Easy Section: 12.1.A Learning objective: Reaction Kinetics 3. A zero-order reaction's rate is dependent on the ______. Ans: C Level of Difficulty: Easy Section: 12.1.B Learning objective: Reaction Kinetics

4. A two-substrate enzymatic reaction in which one product is produced before the second substrate binds to the enzyme has a ______ mechanism. Ans: D Level of Difficulty: Easy Section: 12.1.D Learning objective: Reaction Kinetics 5. The type of enzyme inhibition in which Vmax is unaffected is ______. Ans: K Level of Difficulty: Moderate Section: 12.2.A Learning objective: Enzyme Inhibition 6. In uncompetitive inhibition, the inhibitor binds only to the ______. Ans: F Level of Difficulty: Moderate Section: 12.2.B Learning objective: Enzyme Inhibition 7. A common type of covalent modification of regulatory enzymes involves ______ of serine residues. Ans: L Level of Difficulty: Moderate Section: 12.3.B Learning objective: Control of Enzyme Activity 8. A lead compound for a new drug should bind to its target protein with a very ______. Ans: M Level of Difficulty: Moderate Section: 12.4.A Learning objective: Drug Design 9. Different enzymes that catalyze the same reaction are known as ______. Ans: A

Level of Difficulty: Easy Section: 12.3.B Learning objective: Control of Enzyme Activity 10. In ______, the inhibitor binds to a site involved in both substrate binding and catalysis. Ans: H Level of Difficulty: Easy Section: 12.2.C Learning objective: Enzyme Inhibition

Multiple Choice
11. A lead compound would be most promising if it had: A) KI = 4.7 x 105 M. B) KI = 1.5 x 108 M. C) KI = 1.5 x 10-8 M. D) KI = 4.7 x 10-5 M. E) KM = 4.7 x 105 M. Ans: C Level of Difficulty: Moderate Section: 12.4.A Learning objective: Drug Design 12. What is the velocity of a first-order reaction when the reactant concentration is 6 x 10-2 M and the rate constant is 8 x 103 sec-1? A) 1.33 x 105 M-1sec-1 B) 1.33 x 105 Msec C) 7.5 x 10-2 Msec D) 4.8 x 102 Msec-1 E) not enough data are given to make this calculation Ans: D Level of Difficulty: Moderate Section: 12.1.A Learning objective: Reaction Kinetics 13. Second-order reactions: A) occur when two reactants collide. B) are quite rare. C) have smaller rate constants than first-order reactions.

D) are termolecular. E) are always faster than first-order reactions. Ans: A Level of Difficulty: Easy Section: 12.1.A Learning objective: Reaction Kinetics 14. 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: A) sigmoidal B) pseudo-first-order C) unimolecular D) zero-order E) enzymatic Ans: B Level of Difficulty: Easy Section: 12.1.A Learning objective: Reaction Kinetics 15. KM is: A) a measure of the catalytic efficiency of the enzyme. B) the rate at which the enzyme dissociates from the substrate. C) the rate constant for the reaction ES E + P. D) the [S] that half-saturates the enzyme. E) the rate at which the enzyme binds the substrate. Ans: D Level of Difficulty: Easy Section: 12.1.B Learning objective: Reaction Kinetics 16. In order for an enzymatic reaction obeying the Michaelis-Menten equation to reach 3/4 of its maximum velocity, A) [S] would need to be 2KM B) not enough information is given to make this calculation C) [S] would need to be 50% greater than KM D) [S] would need to be 3KM E) [S] would need to be 3/4KM Ans: D Level of Difficulty: Moderate

Section: 12.1.C Learning objective: Reaction Kinetics 17. The KM can be considered to be the same as the dissociation constant KS for E + S binding if: A) this statement cannot be completed because KM can never approximate KS. B) ES E + P is fast compared to ES E + S. C) the turnover number is very large. D) k2 << k-1. E) kcat/KM is near the diffusion-controlled limit. Ans: D Level of Difficulty: Difficult Section: 12.1.C Learning objective: Reaction Kinetics 18. Find kcat for a reaction in which Vmax is 4 x 10-4 molmin-1 and the reaction mixture contains one microgram of enzyme (the molecular weight of the enzyme is 200,000 D). A) 2 x 10-11 min-1 B) 8 x 107 min-1 C) 8 x 109 min-1 D) 2 x 10-14 min-1 E) 4 x 108 min-1 Ans: B Level of Difficulty: Difficult Section: 12.1.C Learning objective: Reaction Kinetics 19. An enzyme is considered to have evolved to its most efficient form if A) kcat is a large number B) kcat/KM is near the diffusion-controlled limit C) KM is a large number D) kcat/KM is a very small number E) KM is a small number Ans: B Level of Difficulty: Easy Section: 12.1.C Learning objective: Reaction Kinetics 20. Find the initial velocity for an enzymatic reaction when Vmax = 6.5 x 105 molsec1, [S] = 3.0 x 103 M, and KM = 4.5 x 103 M.

A) B) C) D) E)

not enough information is given to make this calculation 2.6 x 105 molsec1 1.4 x 102 molsec1 8.7 x 103 molsec1 3.9 x 105 molsec1

Ans: B Level of Difficulty: Moderate Section: 12.1.C Learning objective: Reaction Kinetics 21. When [S] = KM, 0 = _____Vmax. A) 2 B) 1 C) 0.67 D) 0.5 E) 0.1 Ans: D Level of Difficulty: Easy Section: 12.1.A Learning objective: Reaction Kinetics 22. [S] = KM for a simple enzymatic reaction. When [S] is doubled, the rate becomes _____ Vmax. A) 2 B) 1 C) 0.67 D) 0.5 E) 0.1 Ans: C Level of Difficulty: Easy Section: 12.1.C Learning objective: Reaction Kinetics 23. Irreversible enzyme inhibitors are also called: A) inactivators. B) covalent substrates. C) product inhibitors. D) allosteric effectors. E) Ping Pong inhibitors. Ans: A

Level of Difficulty: Easy Section: 12.2.C Learning objective: Enzyme Inhibition 24. A Lineweaver-Burk plot is also called: A) a sigmoidal plot B) a linear plot C) a doubledisplacement plot D) a MichaelisMenten plot E) a double reciprocal plot Ans: E Level of Difficulty: Easy Section: 12.1.C Learning objective: Reaction Kinetics 25. Parallel lines on a Lineweaver-Burk plot are diagnostic of: A) competitive inhibition. B) non-competitive inhibition. C) allosteric activation. D) allosteric inhibition. E) none of the above. Ans: B Level of Difficulty: Easy Section: 12.2.B Learning objective: Enzyme Inhibition 26. Fourth-order reactions: A) have three or more sequential rate determining steps. B) require a Ping Pong mechanism. C) are best analyzed using Lineweaver-Burk plots. D) are unknown. E) none of the above. Ans: D Level of Difficulty: Moderate Section: 12.1.A Learning objective: Reaction Kinetics 27. If the half-life of a given reaction is constant (not dependant upon the initial conditions), the reaction must be:

A) B) C) D) E)

zeroth order first order second order diffusion controlled enzyme catalyzed

Ans: B Level of Difficulty: Easy Section: 12.1.A Learning objective: Reaction Kinetics 28. Pseudo-first-order reaction kinetics would be observed for the reaction A + B C: A) if [A]=[B] B) if [C]>[A] and [C]>[B] C) if [A] or [B] = 0 D) if [C] = 0 E) none of the above Ans: E Level of Difficulty: Easy Section: 12.1.A Learning objective: Reaction Kinetics The following questions refer to the overall transformation:

29. The overall transformation A) is composed of two elementary reactions. B) can be zeroth order in [S] if [S]>>[E] C) may be described by the Michaelis-Menten equation if certain assumptions are made D) all of the above E) none of the above Ans: D Level of Difficulty: Easy Section: 12.1.B Learning objective: Reaction Kinetics 30. For the reaction, the steady state assumption assumes that A) [S] = [P] B) [ES] is constant C) [P]>>[E]

D) [P] is constant E) k1>>k2 Ans: B Level of Difficulty: Easy Section: 12.1.B Learning objective: Reaction Kinetics 31. The Michaelis constant KM is defined as A) (k1 + k2)/k1 B) (k1 + k1)/k2 C) ([P] + [E])/[ES] D) [ES] E) none of the above Ans: A Level of Difficulty: Easy Section: 12.1.B Learning objective: Reaction Kinetics 32. The most efficient enzymes have kcat/KM values that approach A) k2 B) k1 C) k1 D) k1 + k2 E) 1012 Ms1 Ans: B Level of Difficulty: Easy Section: 12.1.B Learning objective: Reaction Kinetics The following questions refer to the diagram (with boxes where it has been left incomplete):

33. This diagram refers to a: A) Ping Pong reaction. B) ordered bisubstrate reaction. C) random bisubstrate reaction. D) double displacement reaction. E) not enough information is provided. Ans: C Level of Difficulty: Easy Section: 12.1.D Learning objective: Reaction Kinetics 34. Which reactant/product should be in the box labeled with a Z? A) A B) B C) P D) Q E) E Ans: D Level of Difficulty: Easy Section: 12.1.D Learning objective: Reaction Kinetics 35. A compound that reduces the concentration of enzyme available for substrate binding is called: A) a transition-state analog B) a non-competitive inhibitor C) an allosteric effector D) an enzyme inactivator E) a competitive inhibitor

Ans: E Level of Difficulty: Easy Section: 12.2.A Learning objective: Enzyme Inhibition 36. Compounds that function as mixed inhibitors A) interfere with substrate binding to the enzyme B) bind to the enzyme reversibly C) can bind to the enzyme/substrate complex D) all of the above E) none of the above Ans: D Level of Difficulty: Easy Section: 12.2.C Learning objective: Enzyme Inhibition 37. Enzyme activity in cells is controlled by processes including: A) temporary covalent modifications. B) modulation of expression levels. C) feedback inhibition. D) binding to allosteric effectors. E) all of the above. Ans: E Level of Difficulty: Easy Section: 12.3 Learning objective: Control of Enzyme Activity 38. Allosteric activators bind to enzymes A) in a way to inhibit substrate binding. B) and stabilize the T-state, which has a low substrate affinity. C) and stabilize the R-state, which has an enhanced substrate affinity. D) covalently. E) none of the above. Ans: C Level of Difficulty: Easy Section: 12.3.A Learning objective: Control of Enzyme Activity

39. 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 E) all of the above Ans: C Level of Difficulty: Easy Section: 12.3.B Learning objective: Control of Enzyme Activity 40. ________ clinical trials are focused on evaluating the safety of new drug candidates, which cost an average of _______ to bring to market. A) Phase 1; $3 million B) Phase 1; $300 million C) Phase 2; $3 million. D) Phase 2; $300 million E) Phase 3; $30 million Ans: B Level of Difficulty: Easy Section: 12.4.C Learning objective: Drug Design