Chapter 7
The Behavior of Proteins: Enzymes, Mechanisms, and
Control
SUMMARY
Section 7.1
Section 7.2
The two principal models for allosteric enzyme behavior are called the concerted
model and the sequential model.
In the concerted model, the enzyme is thought of as being in a taut form, T, or a
relaxed form, R. All subunits are found in one or the other, and there is an
equilibrium between the T and R forms.
Section 7.3
Many enzymes are controlled by phosphorylation.
Enzymes called kinases use high-energy molecules, such as ATP, to transfer a
phosphate to a specific residue in an enzyme.
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Section 7.4
Zymogens are inactive precursors of an enzyme
A zymogen is converted to the active form by the irreversible cleavage of specific
Section 7.5
The unique orientation of the amino acids in the active site promotes the
catalysis of a chemical reaction.
To understand the catalytic mechanism, the critical amino acids in the active site
Section 7.6
Enzymes are known to catalyze familiar organic chemical reactions.
Other common reactions are general acid-base catalysis and metal-ion catalysis.
Section 7.7
The transition state of an enzyme-catalyzed reaction represents a structure
between the substrates and the products
Transition state analogs are molecules that are shaped to mimic the transition
made, called abzymes. Some abzymes have been made for use in medicine.
Section 7.8
Coenzymes are nonprotein substances that take part in enzymatic reactions and
are regenerated for further reaction.
The Behavior of Proteins: Enzymes, Mechanisms, and
Control 3
LECTURE NOTES
There are two major topics covered in this chapter, and they each deserve a
lecture, at least. The first lecture should be devoted to enzyme control mechanisms,
especially allosteric enzymes. Covalent control of enzymes fits well here, as many
enzymes utilize both control systems. Other mechanistic concepts, such as zymogens
LECTURE OUTLINE
I. Behavior of allosteric enzymes
A. Variance from the Michaelis-Menten model
B. Control mechanisms
1. Feedback inhibition
2. Allosteric effectors (K vs. V systems, homo & heterotropic)
II. Behavioral models
III. Control of enzymes by phosphorylation
IV. Zymogens
V. Nature of active sites
A. Essential residues
VI. Chemical reactions involved in enzyme mechanisms
A. Nucleophilic substitutions
ANSWERS TO PROBLEMS
7.1 The Behavior of Allosteric Enzymes
1. Allosteric enzymes display sigmoidal kinetics when rates are plotted versus
substrate concentration. Michaelis–Menten enzymes exhibit hyperbolic kinetics.
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3. ATP acts as a positive effector of ATCase, and CTP acts as an inhibitor.
4. The term KM should be used for enzymes that display Michaelis–Menten kinetics.
Thus, it is not used with allosteric enzymes. Technically, competitive and
noncompetitive inhibition are also terms that are restricted to Michaelis–Menten
5. A K system is an allosteric enzyme in which the binding of inhibitor alters the
apparent substrate concentration needed to reach one-half Vmax, S0.5.
6. A V system is an allosteric enzyme in which the binding of inhibitor changes the
Vmax of the enzyme but not the S0.5.
7. Homotropic effects are allosteric interactions that occur when several identical
molecules are bound to a protein. The binding of substrate molecules to different
8. ATCase is made up of two different types of subunits. One of them is the
9. Enzymes that exhibit cooperativity do not show hyperbolic curves of rate versus
substrate concentration. Their curves are sigmoidal. The level of cooperativity
can be seen by the shape of the sigmoidal curve.
10. Inhibitors make the shape of the curve more sigmoidal.
7.2 The Concerted and Sequential Models for Allosteric Enzymes
14. In the concerted model, all the subunits in an allosteric enzyme are found in the
same form, either the T form or the R form. They are in equilibrium, with each
The Behavior of Proteins: Enzymes, Mechanisms, and
Control 5
16. Greater cooperativity is favored by having a higher ratio of the T/R form. It is also
favored by having a higher dissociation constant for the substrate binding to the
T form.
19. Scientists looked for drugs that would mimic the behavior of signaling molecules,
such as hormones and neurotransmitters.
20. Side effects occur because the drug that is meant to effect one type of receptor
will likely affect several others unintentionally.
21. First, allosteric effectors modulate the response in a more subtle way than
GABA. When Valium is bound, the response to GABA goes up many fold.
23. Taking too much Valium is not as deadly as taking too much Phenobarbital as it
is not Valium that causes a direct effect, rather it modulates the effect of the
Pfizer called Maraviroc. It interferes with HIV entry into the cells.
7.3 Control of Enzyme Activity by Phosphorylation
25. A kinase is an enzyme that phosphorylates a protein using a high-energy
phosphate, such as ATP, as the phosphate donor.
26. Serine, threonine, and tyrosine are the three most often phosphorylated amino
27. The allosteric effect can be faster because it is based on simple binding
equilibrium. For example, if AMP is an allosteric activator of glycogen
phosphorylase, the immediate increase in AMP when muscles contract can
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28. As part of the mechanism, the sodium–potassium ATPase has an aspartate
residue that becomes phosphorylated. This phosphorylation alters the
conformation of the enzyme and causes it to close on one side of the membrane
and open on the other, moving ions in the process.
29. Glycogen phosphorylase is controlled allosterically by several molecules. In the
7.4 Zymogens
32. The digestive enzymes trypsin and chymotrypsin are classic examples of
regulation by zymogens. The blood-clotting protein thrombin is another.
33. Trypsin, chymotrypsin, and thrombin are all proteases. Trypsin cleaves peptide
34. Caspases are a family of homodimer cysteine proteases responsible for many
35. Chymotrypsinogen is an inactive zymogen. It is acted upon by trypsin, which
cleaves peptides at basic residues, like arginine. When trypsin cleaves between
36. Zymogens are often seen with digestive enzymes that are produced in one tissue
and used in another. If the enzyme were active immediately upon production, it
37. This allows for a more rapid response when the hormone is needed. The
38. Apoptosis is a natural phenomenon of programmed cell death.
39. Disruption of apoptosis can lead to forms of cancer and unwanted cell death,
such as cells surrounding neurons that have died from a stroke.
The Behavior of Proteins: Enzymes, Mechanisms, and
Control 7
7.5 The Nature of the Active Site
40. Serine and histidine are the two most critical amino acids in the active site of
chymotrypsin.
41. The initial phase releases the first product and involves an acylenzyme
42. In the first step of the reaction, the serine hydroxyl is the nucleophile that attacks
43. Histidine 57 performs a series of steps involving general base catalysis followed
by general acid catalysis. In the first phase, it takes a hydrogen from serine 195,
44. The first phase is faster for several reasons. The serine at position 195 is a
strong nucleophile for the initial nucleophilic attack. It then forms an acyl–enzyme
45. Histidine 57 exists in both the protonated and unprotonated form during the
chymotrypsin reaction. Its pKa of 6.0 makes this possible in the physiological pH
range.
46. Instead of a phenylalanine moiety (similar to the usual substrates of
7.6 Chemical Reactions Involved in Enzyme Mechanisms
47. They act as Lewis acids (electron-pair acceptors) and can take part in enzyme
catalysis mechanisms of enzymes.
50. SN1 stands for unimolecular nucleophilic substitution. The unimolecular part
means that it obeys first-order kinetics. If the reaction is R:X + Z: R:Z + X:, with
51. The SN1 reaction leads to loss of stereospecificity as the X group leaves before
the entering nucleophile. This means that the nucleophile can enter from different
angles, leading to different isomers.
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52. The results do not prove that the mechanism is correct, because results from
7.7 The Active Site and Transition States
53. A good transition-state analogue would have to have a tetrahedral carbon atom
54. The induced-fit model assumes that the enzyme and substrate must both move
and change to conform to each other perfectly. Thus, the true fit is not between
55. An abzyme is created by injecting a host animal with a transition-state analogue
of a reaction of interest. The host animal makes antibodies to the foreign
56. Cocaine blocks the reuptake of the neurotransmitter dopamine at synapses.
Thus, dopamine stays in the system longer, overstimulating the neuron and
57. Cocaine can be degraded by a specific enzyme that hydrolyzes an ester bond
that is part of cocaine’s structure. In the process of this hydrolysis, the cocaine
7.8 Coenzymes
58. Nicotinamide adenine dinucleotide, oxidation–reduction; flavin adenine
59. Most coenzymes are derivatives of compounds we call vitamins. For example,
nicotinamide adenine dinucleotide is produced from the B vitamin niacin. Flavin
adenine dinucleotide comes from riboflavin.
61. Coenzymes can accomplish the same mechanisms that the amino acids do in a
reaction. For example, a metal ion may act as a general acid or base. Parts of a
The Behavior of Proteins: Enzymes, Mechanisms, and
Control 9
62. Yes, there would be a preference. Because the coenzyme and the other
63. Green chemistry refers to the modern techniques that replace large quantities of
toxic chemicals previously used with smaller quantities of less toxic chemicals