Chapter 4: Enzymes

Enzyme inhibitors are molecules that interact in some way with the enzyme to prevent it from working in the normal manner. There are a variety of types of inhibitors including: nonspecific, irreversible, reversible - competitive and noncompetitive. Poisons and drugs are examples of enzyme inhibitors. As a pharmacist you will need to understand how these enzymes function so that you can design your drugs accordingly. For example: Disulfiram (Antabuse) is a drug used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. When you drink too much alcohol after a huge party, the toxic ethanol is metabolized in the body by oxidation to acetaldehyde, which is in turn further oxidized to acetic acid by aldehyde oxidase enzymes. Normally, the second reaction is rapid so that acetaldehyde does not accumulate in the body. A drug, disulfiram (Antabuse) inhibits the aldehyde oxidase which causes the accumulation of acetaldehyde with subsequent unpleasant side-effects of nausea and vomiting. This drug is sometimes used to help people overcome the drinking habit.

Methanol poisoning occurs because methanol is oxidized to formaldehyde and formic acid which attack the optic nerve causing blindness. Ethanol is given as an antidote for methanol poisoning because ethanol competitively inhibits the oxidation of methanol. Ethanol is oxidized in preference to methanol and consequently, the oxidation of methanol is slowed down so that the toxic by-products do not have a chance to accumulate.

AZT (retrovir or zidovudine) was a major breakthrough in AIDS therapy in the 1990s that significantly altered the course of the illness and helped destroy the notion of the 1980s and early 90s that HIV/AIDS was an instant death sentence. AZT competitively inhibits reverse transcriptase, an enzyme required by HIV to replicate itself.

If you want some animations click here:
(1) Activation energy to start a reaction
(2) Enzymes undergo Conformation change
(3) Enzymes bring Substrates into closer proximty and correct orientation
(4) Enzymes catalyze rxns without being used and stabilise chemical reactions
(5) Allosteric enzymes can respond to cellular needs and demands

Now test yourself

1. Enzymes are a special type of

1. carbohydrates
2. lipids
3. proteins
4. inorganic compounds

2. A catalyst is a substance which

1. increases the rate of a chemical reaction but is itself unchanged by the reaction
2. is toxic to most cells
3. is composed mostly of lipids
4. does not usually participate in any chemical reactions

3. The molecule to which an enzyme joins is called its

1. coenzyme
2. catalyst
3. target molecule
4. substrate

4. Coenzymes are best defined as

1. organic molecules which can serve as substitutes for enzymes
2. inorganic molecules which can serve as substitutes for enzymes
3. organic molecules which help in enzyme-catalyzed reactions by bonding with electrons
4. inorganic molecules which help in enzyme-catalyzed reactions by bonding with electrons

5. State how the following will affect the rate of an enzyme reaction.

1. increasing temperature
2. decreasing temperature
3. pH
4. substrate concentration

6. State four characteristics of enzymes.

7. Briefly describe a generalized enzyme-substrate reaction, state the function of an enzyme's active site, and describe how an enzyme is able to speed up chemical reactions.

8. Correctly complete the following statements with a term that makes me happy.

8.1. _______________ is the energy needed to start a chemical reaction.

8.2. The amino acid sequence of a polypeptide chain best describes the _______________ structure of the polypeptide chain.

8.3. The substrate bonds to a specific area on the enzyme molecule known as the enzyme's _______________.

8.4. Compounds similar in shape to an enzyme's substrate, that can compete with the substrate molecules by binding with the active site of the enzyme are said to be _______________.

8.5. The optimum pH for most human metabolic enzyme catalyzed reactions is _____.

8.6. The optimum temperature for most human metabolic enzyme catalyzed reactions is ____ °C.

8.7. An inactive form of an enzyme is called a(n) __________________.

9. Multiple Choice Section: Choose the response which best completes the following statements or answers the following questions.

9.1. The disorder of a system is measured by its (1.) activation energy (2.) heat of reaction (3.) entropy (4.) energy (5.) enteron

9.2. Which is the optimum pH of most human enzymes? (1.) 1 (2.) 2 (3.) 5 (4.) 7 (5.) 10

Base your answers to questions 9.3 and 9.4 below on the reading passage that follows and your knowledge in biology. A student ground 1 gram of fresh liver in a mortar, placed the ground liver in a test tube, and added 1 ml of peroxide. The gas that was generated was collected. A glowing splint burst into flames when placed in the gas. The student then repeated the procedure, using one gram of boiled liver and one gram of liver treated with a strong acid. When peroxide was added to each sample of liver, no gas was generated.

9.3. The gas that was generated was most likely (1.) oxygen (2.) nitrogen (3.) carbon dioxide (4.) hydrogen (5.) ammonia (6.) water vapor

9.4. If the substance in the liver that acted on the peroxide was an enzyme, it could (1.) be recovered from the living tissue that had not been boiled or treated with acid after the reaction ceased (2.) not be recovered because it was consumed while engaging in its catalytic reaction activities (3.) not be recovered because there is no enzyme in liver that catalyzes the breakdown of peroxide (4.) not be recovered because grinding would break up the molecule (5.) be recovered only before the peroxide was added

9.5. The “lock and key” model of enzyme action illustrates that a particular enzyme molecule (1) forms a permanent enzyme-substrate complex (2) may be destroyed and resynthesized several times (3) interacts with a specific type of substrate molecule (4) reacts at identical rates under all conditions

9.6. An enzyme-substrate complex may result from the interaction of molecules of (1) glucose and lipase (2) fat and amylase (3) sucrose and maltase (4) protein and protease

9.7. The part of the enzyme molecule into which the substrate fits is called the (1) active site (2) coenzyme (3) polypeptide (4) protease

9.8. Which of the following variable is LEAST likely to affect an enzymes rate of reaction? (1) temperature (2) pH (3) carbon dioxide concentration (4) enzyme concentration

9.9. Which would least affect the effectiveness of an enzyme? (1.) temperature (2.) concentration of the substrate (3.) concentration of the enzyme (4.) original activation energy of the system (5.) pH

9.10. Which is most similar to the process of competitive inhibition? (1.) When you are about to park your car in your spot, a bulldozer comes along and smashes your car away from the spot. (2.) When you arrive at work in the morning, you are unable to park your car in your assigned parking spot because someone has placed a giant cement block in front of your spot. (3.) When you arrive at work in the morning, you are unable to park your car in your assigned parking spot because the car of the person next to you has taken up just enough space that you can not fit your own car in. (4) When you arrive at work in the morning, you are unable to park your car in your parking spot, because someone with a car exactly like yours has already taken your spot, leaving you nowhere to park your car.

9.11. Which of the following is characteristic of enzymes?
1) They lower the energy of activation of a reaction by binding the substrate.
2) They raise the energy of activation of a reaction by binding the substrate.
3) They lower the amount of energy present in the substrate.

9.12. An enzyme is generally named by adding ____ to the end of the name of the _____.
1) "-ose". cell in which it is found 2) "-ase". cell in which it is found
3) "-ose". substrate 4) "-ase". substrate 5) "-ase". coenzyme

9.13. Which statement describes the currently accepted theory of how an enzyme and its substrate fit together?
1) As the product is released, the enzyme breaks down.
2) The enzyme is like a key that fits into the substrate, which is like a lock.
3) The active site is permanently changed by its interaction with the substrate.
4) As the substrate binds to the enzyme, the shape of the enzyme site changes to accommodate the reaction.

9.14. Which statement is Not true about the effects of various conditions on the activity of an enzyme?
1) Higher temperatures generally increase the activity of an enzyme up to a point.
2) Above a certain range of temperatures, the protein of an enzyme is denatured.
3) A change in pH can cause an enzyme to be inactivated.
4) An enzyme's activity is generally reduced by an increase in substrate concentration.
5) When sufficient substrate is available, the active site will nearly always by occupied.

9.15. Which statement is Not true about enzyme inhibition?
1) In competitive inhibition, the inhibitor binds to the active site of the enzyme.
2) In noncompetitive inhibition, the inhibitor binds to the allosteric site of the substrate.
3) In irreversible inhibition, a poison binds to the enzyme so that it can never work again.
4) Most inhibitors act in a reversible fashion.
5) All of the above statements are true.

9.16. Consider this reaction. A + B --> C + D + energy.
1) This reaction is exergonic. 2) An enzyme could still speed the reaction.
3) ATP is not needed to make the reaction go.
4) A and B are reactants; C and D are products.
5) All of these are correct.

9.17. The active site of an enzyme
1) is similar to that of any other enzyme.
2) is the part of the enzyme where its substrate can fit.
3) can be used over and over again.
4) is not affected by environmental factors like pH and temperature.
5) Both B and C are correct.

9.18. An allosteric site on an enzyme is
1) the same as the active site. 2) nonprotein in nature.
3) where ATP attaches and gives up its energy.
4) often involved in feedback inhibition. 5) All of these are correct.

9.19. A student conducts an experiment to test the efficiency of a certain enzyme. Which would probably not result in a change in the enzyme's efficiency? 1) Bringing the temperature of the experimental setup from 20 degrees C to 50 degrees C.
2) Adding an acidic solution to the setup. 3) Adding more substrate but not enzyme.
4) Placing the substrate and enzyme in a container with double the capacity.
5) Adding enzyme but not substrate.

9.20. Which of the following statements about enzymes is Not True?
1) Competitive inhibitors act away from the active site.
2) Allosteric inhibitors act away from the active site.
3) Allosteric inhibitors can change the size of the active site.
4) Competitive inhibitors usually resemble the substrate.
5) Noncompetitive inhibitors are allosteric inhibitors.

9.21. In noncompetitive inhibition, the allosteric inhibitor
1) attaches to the active site, preventing the substrate from attaching there.
2) attaches to the substrate, preventing it from attaching to the active site.
3) changes the pH of the environment, thus preventing enzyme-substrate complex formation.
4) causes the substrates to polymerize, preventing individual enzyme-substrate attachment.
5) attaches to the enzyme at a site away from the active site, altering the shape of the enzyme.

9.22. Which of the following statements is Not True about all enzymes?
1) are proteins. 2) lower the activation energy of reactions.
3) operate at the same optimum pH.
4) can be identified because their names end in - ase.
5) require a coenzyme/cofactor to work effectively.

9.23. In an endergonic reaction, the products of a reaction contain
1) more energy than the reactants, and energy is released.
2) more energy than the reactants, and energy must be supplied.
3) less energy than the reactants, and energy is released.
4) less energy than the reactants, and energy must be supplied.
5) the same amount of energy than the reactants, but due to the presence of an enzyme, energy is released.

9.24. Physicists have defined a formal measure of disorder, called
1) randomness 2) displacement 3) entropy 4) disorganization 5) None of the above.

9.25. The minimum amount of energy needed for a process to occur is called the
1) minimal energy theory 2) process energy 3) kinetic energy 4) activation energy 5) None of the above.

9.26. An inhibitor that changes the overall shape and chemistry of an enzyme is known as a(n)
1) allosteric inhibitor 2) competitive inhibitor 3) steric inhibitor 4) noncompetitive inhibitor 5) None of the above.

10. Another Quiz on Enzyme Kinetics - Steady State
10.1. Which of the statements regarding enzymes is false?
A	Enzymes are proteins that function as catalysts.
B	Enzymes are specific.
C	Enzymes provide activation energy for reactions.
D	Enzyme activity can be regulated.
E	Enzymes may be used many times for a specific reaction.
10.2. The relationship between an enzyme and a reactant molecule can best be described as:
A	a temporary association.
B	an association stabilized by a covalent bond.
C	one in which the enzyme is changed permanently.
D	a permanent mutual alteration of structure.
E	noncomplementary binding.
10.3. When [S] = KM, the velocity of an enzyme catalyzed reaction is about:
A	0.1*Vmax.
B	0.2*Vmax.
C	0.3*Vmax.
D	0.5*Vmax.
E	0.9*Vmax.
10.4. The active site of an enzyme
A	remains rigid and does not change shape.
B	is found at the center of globular enzymes.
C	is complementary to the rest of the molecule.
D	contains amino acids without sidechains.
E	None of the above choices are correct.
10.5. The active site of an enzyme differs from an antibody-antigen binding site in that the enzyme active site
A	contains modified amino acids.
B	catalyzes a chemical reaction.
C	is complementary to a specific ligand.
D	contains amino acids without sidechains.
E	None of the above are correct.

11. A few more multiple choice questions

11.1. Chemical reactions fuel the life processes in living things.

A. True

B. False

11.2. _________ speed up chemical reactions.

A. Enzymes

B. Catalysts

C. Both A and B

D. Neither A nor B

11.3. Enzymes are composed of ________.

A. carbohydrate

B. lipid

C. nucleic acid

D. protein

11.4. Molecules that react with one another to form a new product are called ________.

A. reactants

B. active molecules

C. inactive molecules

D. products

11.5. The enzyme hexokinase binds to ________.

A. water

B. oxygen

C. glucose

D. maltose

11.6. The amount of energy needed for a specific chemical reaction to take place is known as

________.

A. reaction energy

B. chemical energy

C. energy of absorption

D. energy of activation

Assignment 2: 23 years ago Zidovudine (AZT) was the first drug approved for the treatment of HIV. Many thought that AZT would be the cure for HIV/AIDS but it has met its challenges. How does AZT work and why is it not a cure we were waiting for? (include rough sketches of how its Lineweaver-burke and Michaelis-Menten inhibition graphs would look like). Due date 15 February 2009 (Valentines Gift)