Ch. 6: An Introduction to Metabolism

the only way to increase the rate of product info when all enzyme molecules have occupied active sites (lots of substrate is available) is to...

+ more enzyme

You have recently isolated an HIV protease, an enzyme that is responsible for catalyzing reactions that produce functional viral proteins. You analyze the active site of the enzyme and find that the site is lined with negative (-) charges. Which kind of amino acids would you likely find comprising a portion of the substrate molecule that interacts with the active site?

amino acids w/ positively charged R group to make ionic bonds

catabolism

break down complex molecules into simpler compounds

thermodynamics

the study of energy transformations

energy coupling

using an exergonic process to drive an endergonic 1 - how cells manage energy resources

2 laws of thermodynamics

- 1 = energy of the universe is constant/conserved; it can be transferred & transformed but not created nor destroyed - 2 = every energy transfer increases entropy (disorder) of universe; No energy transfer is 100% efficient, some energy is lost as heat

ATP cycle

- ATP is renewable, regenerated addition of a phosphate group to ADP - Energy to phosphorylate ADP comes from catholic rxns in the cell - Chemical potential energy temporarily stored in ATP drives most cellular work

metabolic pathway

- Begins w/ a specific molecule & ends w/ a product - Each step is catalyzed by a specific enzyme

factors that can affect enzyme activity

- Environmental factors (temp & pH) - Chemicals

example of chemical work conversion reaction alone then coupled w/ ATP hydrolysis

- Glutamic acid + ammonia → glutamine coupled: - glutamic acid + ATP → phosphorylated intermediate + ADP - ammonia displaces the phosphate group, forming glutamine + ADP + phosphate group - alone, nonspontaneous, coupled spontaneous

Active site can lower EA & speed up rxn by...

- Orienting substrates correctly - Straining substrate bonds (stabilize transition state) - Providing favorable microenvironment - Covalently bonding to substrate (participate in rxn)

exergonic rxn

- RELEASES energy that can perform work - spontaneous - negative ΔG - catabolism

endergonic rxn

- REQUIRES energy to perform work - non spontaneous - positive ΔG - anabolism

metabolism

- Totality of an organism's chemical rxns - An emergent property of life that arises from interactions between molecules w/ in cell

3 examples of free energy change w/ explanations

- gravitational motion: objects move spontaneously from higher altitude → lower one - diffusion: molecules diffuse until they are randomly dispersed - chemical rxn: a sugar molecule is broken down → simpler molecules in a cell

categorization of enzyme inhibitors

- irreversible - reversible (2 types - competitive & noncompetitive)

how do enzymes catalyze rxns?

- lower activation energy (EA) barrier - Enzymes don't affect the change in free-energy (ΔG), instead they hasten rxns that would occur normally

Allosteric regulation

- protein's function @ 1 site is affected by the binding of a regulatory molecule at another site - May either stimulate or inhibit an enzyme's activity - Most allosterically regulated enzymes are made from 2+ polypeptide subunits

mechanical work

ATP binds noncovalently to motor proteins and then is hydrolyzed, causing a shape change that walks the motor protein forward

transport work

ATP phosphorylates transport proteins, causing a shape change that allows transport of solutes

As a result of its involvement in a reaction, an enzyme _____. a) permanently alters its shape. b) is unchanged c) loses energy d) loses a phosphate group e) is used up

B

Thermal energy (heat)

KE; random movement of atoms or molecules

Chemical energy

PE available for release in a chemical reaction

inorganic factors

Tightly bound - Iron (in heme groups), zinc, copper

In general, the hydrolysis of ATP drives cellular work by __________. a) releasing free energy that can be coupled to other reactions b) yielding free phosphate c) releasing heat d) acting as a catalyst e) lowering the free energy of the reaction

a

Most cells cannot harness heat to perform work because __________. a) temperature is usually uniform throughout a cell b) heat is not a form of energy c) cells do not have much heat; they are relatively cool d) heat can never be used to do work e) heat must remain constant during work

a

The process of stabilizing the structure of an enzyme in its active form by the binding of a molecule is an example of __________. a) allosteric regulation b) feedback inhibition c) competitive inhibition d) noncompetitive inhibition e) cooperativity

a

Which of the following best characterizes the functional role of ATP in cellular metabolism? a) The free energy released by ATP hydrolysis is coupled to endergonic processes via the formation of a phosphorylated intermediate. b) The release of free energy during the hydrolysis of ATP heats the surrounding environment. c) ATP is catabolized to carbon dioxide and water. d) The ΔG associated with ATP hydrolysis is positive. e) Hydrolysis of ATP releases a large amount of free energy because the nonpolar phosphate groups are repelled by water.

a

Which of the following is an endergonic reaction? a) Glucose + fructose → sucrose b) HCl → H+ + Cl c) C6H12O6 + 6 O2 → 6 CO2 + 6 H2O d) ATP → ADP + inorganic phosphate e) All of the listed responses are correct.

a

Which of the following metabolic processes can occur without a net influx of energy from some other process? a) C6H12O6 + 6 O2 → 6 CO2 + 6 H2O b) ADP + Pi → ATP + H2O c) 6 CO2 + 6 H2O → C6H12O6 + 6 O2 d) amino acids → protein e) glucose + fructose → sucrose

a

Which of the following statements about the active site of an enzyme is correct? a) The active site may resemble a groove or pocket in the surface of a protein into which the substrate fits. b) The active site has a fixed structure (shape). c) Coenzymes are rarely found in the active site of an enzyme. d) The structure of the active site is not affected by changes in temperature. e) The active site allows the reaction to occur under the same environmental conditions as the reaction without the enzyme.

a

cooperativity

a form of allosteric regulation that can amplify enzyme activity through binding of 1 substrate molecule to active site of 1 subunit that locks all subunits in active conformation

a) if a drug binds to an active site & does not reduce efficacy of inhibition by high substrate concentration is it likely a competitive inhibitor? b) what about if it binds to an active site & reduces efficacy of inhibition by high substrate concentration? c) what about if it doesn't bind to an active site & reduces efficacy of inhibition by high substrate concentration?

a) no, likely an irreversible inhibitor b) yes c) no, likely a noncompetitive (reversible) inhibitor

A substrate binds to an enzyme at the ____, where the reaction occurs.

active site

The competitive inhibitor competes with the substrate for the active site ___ on the enzyme

active site

An enzyme _____. a) is a source of energy for endergonic reactions b) is an organic catalyst c) is a inorganic catalyst d) increases the EA of a reaction e) can bind to nearly any molecule

b

Metabolic pathways in cells are typically far from equilibrium. Which of the following processes tend(s) to keep these pathways away from equilibrium? a) All of the listed choices are correct. b) The continuous removal of the products of a pathway to be used in other reactions and the input of free energy from outside the pathway c) The continuous removal of the products of a pathway to be used in other reactions d) An input of free energy from outside the pathway e) An input of heat from the environment

b

Organisms are described as thermodynamically open systems. Which of the following statements is consistent with this description? a) The metabolism of an organism is isolated from its surroundings. b) Organisms acquire energy from, and lose energy to, their surroundings. c) Because energy must be conserved, organisms constantly recycle energy and thus need no input of energy. d) Heat produced by the organism is conserved in the organism and not lost to the environment. e) All of the listed responses are correct.

b

What do the sign and magnitude of the ΔG of a reaction tell us about the speed of the reaction? a) The more negative the ΔG, the faster the reaction is. b) Neither the sign nor the magnitude of ΔG has anything to do with the speed of a reaction. c) The sign determines whether the reaction is spontaneous, and the magnitude determines the speed. d) The sign does not matter, but the larger the magnitude of ΔG, the faster the reaction. e) The sign does not matter, but the smaller the magnitude of ΔG, the faster the reaction.

b

Which of the following correctly states the relationship between anabolic and catabolic pathways? a) The flow of energy between catabolic and anabolic pathways is reversible. b) Anabolic pathways synthesize more complex organic molecules using the energy derived from catabolic pathways. c) Degradation of organic molecules by anabolic pathways provides the energy to drive catabolic pathways. d) Energy derived from catabolic pathways is used to drive the breakdown of organic molecules in anabolic pathways. e) Catabolic pathways produce usable cellular energy by synthesizing more complex organic molecules.

b

Which of the following determines the sign of ΔG for a reaction? a) The free energy of the reactants b) The free energy of the reactants and the free energy of the products c) The affinity of the enzyme for the reactants d) The enzyme concentration e) The free energy of the products

b

You have added an irreversible inhibitor to a sample of enzyme and substrate. At this point, the reaction has stopped completely. What can you do to regain the activity of the enzyme? a) Removing the irreversible inhibitor should get the reaction working again. b) The enzyme is inactive at this point. New enzyme must be added to regain enzyme activity. c) Adding more substrate will increase the rate of reaction. d) Adding more inhibitor should get the reaction up to speed again.

b

You have an enzymatic reaction proceeding at the optimum pH and optimum temperature. You add a competitive inhibitor to the reaction and notice that the reaction slows down. What can you do to speed the reaction up again? a) Add more inhibitor to speed up the reaction. b) Add more substrate; it will outcompete the inhibitor and increase the reaction rate. c) Increase the temperature. d) Increase the pH.

b

The energy available to do work can be measured for both reactants and products of a given reaction. For the reaction A + B yields C + D, it is found that the free energy of the reactants is G= 13 kcal/mol. The free energy of the products is G= 28 kcal/mol. If this reaction were coupled to the hydrolysis of an ATP under cellular conditions, which of the following would be true? A. The net reaction would be spontaneous B. The net reaction would be nonspontaneous C. The net reaction would be exergonic D. The net reaction would be endergonic

b & d *-ΔG = spontaneous & exergonic & +ΔG = nonspontaneous & endergonic; final 28- initial 13 = 15 -7.3 for ATP hydrolysis = 7.7

The following graph shows the change in free energy as a reaction progresses. Which of the following statements are correct? A. This reaction releases energy. B. This reaction requires energy C. This is an endergonic reaction. D. This is an exergonic reaction. E. The ΔG for this reaction is negative. F. The ΔG for this reaction is positive. G. An example of this type of reaction is creation of peptide bonds between amino acids to make a protein.

b, c, f, & g b - reactants at lower energy level than products = require E c - already determined this rxn required energy f - energy increases between reactants → products g - gains energy = anabolic reaction = building bonds

Competitive inhibitors

bind to active site of enzyme, competing w/ substrate; can be overcome by increasing concentration of substrate

Noncompetitive inhibitors

bind to another part of an enzyme, causing it to change shape & making active sites less effective

Induced fit of a substrate

brings chemical groups of active site into positions that enhance their ability to catalyze chemical rxns

anabolism

build complex molecules from simpler ones - Anabolic pathways synthesize complex molecules using energy from catabolic pathways

A chemical reaction is designated as exergonic rather than endergonic when __________. a) activation energy exceeds net energy release b) it absorbs more energy c) the potential energy of the products is less than the potential energy of the reactants d) activation energy is required e) the products are less complex than the reactants

c

Choose the pair of terms that correctly completes this sentence: Catabolism is to anabolism as __________ is to __________. a) work; energy b) entropy; enthalpy c) exergonic; endergonic d) exergonic; spontaneous e) free energy; entropy

c

Consider a situation in which the enzyme is operating at optimum temperature and pH, and has been saturated with substrate. What is your best option for increasing the rate of the reaction? a) Increase the pH. b) Increase the temperature. c) Increase the enzyme concentration. d) Increase the substrate concentration.

c

If the entropy of a living organism is decreasing, which of the following is also occurring? a) The first law of thermodynamics is being violated. b) In this situation, the second law of thermodynamics must not apply. c) Energy is being supplied to the organism. d) The entropy of the organism's environment must also be decreasing. e) Heat is being used by the organism as a source of energy.

c

Much of the suitability of ATP as an energy intermediary is related to the instability of the bonds between the phosphate groups. These bonds are unstable because __________. a) the phosphate groups are nonpolar and are repelled by water in the cell b) the bonds between the phosphate groups are unusually strong and breaking them releases free energy c) the negatively charged phosphate groups vigorously repel one another and the terminal phosphate group is more stable in water than it is in ATP d) the valence electrons in the phosphorus atom have less energy on average than those of other atoms e) they are hydrogen bonds, which are only about 10% as strong as covalent bonds

c

Which of these statements about enzyme inhibitors is true? a) When the product of an enzyme or an enzyme sequence acts as its inhibitor, this is known as positive feedback. b) Inhibition of enzyme function by compounds that are not substrates is something that only occurs under controlled conditions in the laboratory. c) The action of competitive inhibitors may be reversible or irreversible. d) A competitive inhibitor binds to the enzyme at a place that is separate from the active site. e) A noncompetitive inhibitor does not change the shape of the active site.

c

Use the graph and your knowledge of enzymes to identify the three true statements about enzymes. a) Only reactions that are controlled by enzymes require activation energy. b) Chemical reactions cannot occur without enzymes. c) Enzymes lower the overall energy input needed for a reaction to occur. d) By binding to reactant molecules, enzymes make it easier for the bonds in the molecules to break apart. e) Reactants cannot convert to products without an initial input of energy to start the reaction.

c-e

energy

capacity to cause change - Exists in various forms, some of which can perform work - Can be converted from 1 form to another

An enzyme is considered a ___ because it speeds up chemical reactions without being used up.

catalyst

enzyme

catalytic protein

catalyst

chemical agent that speeds up a rxn w/o being consumed by rxn

3 types of work that a cell does

chemical, transport, mechanical

a ___ such as a vitamin, binds to an enzyme and plays a role in catalysis.

cofactor

a(n) ___ inhibitor has a structure that is so similar to the substrate that it can bond to the enzyme just like the substrate.

competitive

When properly aligned, the enzyme and substrate form an enzyme-substrate (ES) ____

complex

Enzyme activity is affected by pH because __________. a) most substrates don't function well at high or low pH b) low pH will denature all enzymes c) changes in pH cause loss of all cofactors from enzymes d) high or low pH may disrupt hydrogen bonding or ionic interactions and thus change the shape of the enzyme's active site may not be enough energy to overcome the activation energy barrier e) the binding of hydrogen ions to the enzyme absorbs energy and thus there

d

The formation of glucose-6-phosphate from glucose is an endergonic reaction and would, therefore, be coupled to which of the following reactions or pathways? a) The contraction of a muscle cell b) The active transport of a phosphate ion into the cell c) The formation of ATP from ADP and inorganic phosphate d) The hydrolysis of ATP e) The conversion of glucose + fructose to sucrose

d

Which of the following environments or actions would not affect the rate of an enzyme reaction? a) Cooling the enzyme b) Substrate concentration c) pH d) None of the listed responses is correct. e) Heating the enzyme

d

Which of the following statements about enzyme function is correct? a) Enzymes can change the equilibrium point of reactions, but they cannot speed up reactions because they cannot change the net energy output. b) Enzymes can greatly speed up reactions, but they cannot change the activation energy because they cannot change the net energy output. c) None of the listed responses is correct. d) Enzymes can lower the activation energy of reactions, but they cannot change the equilibrium point because they cannot change the net energy output. e) Enzymes can greatly speed up reactions, but they cannot change the net energy output because they cannot change the activation energy.

d

Some bacteria are metabolically active in hot springs because __________. a) they are able to maintain a lower internal temperature b) high temperatures make catalysis unnecessary c) their enzymes are completely insensitive to temperature d) they use molecules other than proteins or RNAs as their main catalysts e) their enzymes have high optimal temperatures

e

The binding of an allosteric inhibitor to an enzyme causes the rate of product formation by the enzyme to decrease. Which of the following best explains why this decrease occurs? a) The allosteric inhibitor binds to the active site, preventing the substrate from binding. b) The allosteric inhibitor causes free energy change of the reaction to increase. c) The allosteric inhibitor lowers the temperature of the active site. d) The allosteric inhibitor binds to the substrate and prevents it from binding at the active site. e) The allosteric inhibitor causes a structural change in the enzyme that prevents the substrate from binding at the active site.

e

What is meant by the "induced fit" of an enzyme? a) The substrate can be altered so that it is induced to fit into the enzyme's active site. b) The enzyme structure is altered so that it can be induced to fit many different types of substrate. c) The presence of the substrate in solution induces the enzyme to slightly change its structure. d) The shape of the active site is nearly perfect for specifically binding the enzyme's substrate(s). e) The enzyme changes its shape slightly as it binds the substrate.

e

Which of the following is changed in a reaction by the action of an enzyme? a) The magnitude of ΔG b) G of the reactants c) The sign of ΔG d) G of the products e) The activation energy

e

feedback inhibition

end product of a metabolic pathway shuts down pathway, preventing cell from wasting chemical resources by synthesizing more product than is needed

Kinetic energy (KE)

energy associated w/ motion or action

Potential energy (PE)

energy that matter possesses bc of its location or structure (stored energy)

When the noncompetitive inhibitor is bonded to the enzyme, the shape of the ____ is distorted

enzyme

an enzyme is ___ when it loses its native conformation and its biological activity.

enzyme

Mechanisms such as ____ enable precise control over a cell's ____ -- all of its chemical reactions.

feedback inhibition; metabolism

overview of cellular respiration

glucose is broken down in a series of exergonic rxns that power the work of the cell

Irreversible inhibitors

inhibitor usually attaches to enzyme by covalent bonds (ex: some toxins & poisons, penicillin)

Free energy of activation/activation energy (EA)

initial energy needs to start a chem rxn; often supplied in form of heat from surroundings

usually, a(n) ___ inhibitor forms a covalent bond with an amino acid side group within the active site, which prevents the substrate from entering the active site or prevents catalytic activity

irreversible

Are living cells at equilibrium?

no - there is a constant flow of materials in and out of the cell - a cell that has reached metabolic equilibrium is dead

a(n) ___ inhibitor binds to a site on the enzyme that is not the active site.

noncompetive

cofactors

nonprotein enzyme helpers

spontaneous rxn

occurs on its own, quickly or slowly (non spontaneous won't occur on its own)

coenzyme

organic cofactors - Vitamins = loosely bound, released as a normal part of the catalytic cycle

In general, enzymes are what kinds of molecules?

proteins

Adenosine triphosphate (ATP)

provides energy for cellular functions

active site

region on the enzyme where the substrate binds

An enzyme is considered ___ because of its ability to recognize the shape of a particular molecule.

specific

ΔG - what does it stand for - formula

stands for free energy change ΔG = G_final state - G_inital state

Enzyme inhibitors disrupt normal interactions between an enzyme and its _____.

substrate

In a catalyzed reaction a reactant is often called a ____

substrate

enzymes bind to ___, forming an ___

substrates (reactant), forming an enzyme-substrate complex