Biochemistry Ch. 13: Introduction to Metabolism

Covalent bonds can be broken in two ways:

A bond between two carbon molecules can be broken through homolytic cleavage and heterolytic cleavage

Lyase

enzymes that catalyze cleavages (or additions in the reverse direction) in which electronic rearrangements occur.

Ligase

enzymes that catalyze condensation reactions in which two atoms are joined, using ATP or other energy source

Which answer choice ranks the four compounds from most reduced to most oxidized?

ethane, ethanol, acetaldehyde, acetic acid

Changes in free energy, enthalpy, and entropy are related to each other quantitatively by the equation ΔG = ΔH − TΔS. By convention, ΔS has a _____ sign when entropy increases, and ΔH has a _____ sign when heat is released by the system to its surroundings.

positive; negative

Because some mRNA transcripts undergo alternative splicing and others are noncoding, it may be more helpful to study the _____ of cancer cells to identify new biomarkers for screening tests.

proteome

Consider the chemical reaction shown, which occurs during lactic acid fermentation. Which molecule is reduced in this reaction?

pyruvate

Q = K'eq

reaction reaches equilibrium

Q < K'eq

reaction will proceed spontaneously from left to right (forward)

Q > K'eq

reaction will proceed spontaneously from right to left (reverse)

Researchers discover that the transport of substrate across intracellular membranes may be the limiting factor in an enzyme-catalyzed reaction. This is an example of:

sequestering an enzyme into a subcellular organelle.

A small change in the concentration of substrate, or of an allosteric effector, can have a large impact on reaction rate in the _____of a _____ curve.

steepest part; sigmoid

Consider the chemical reaction shown, which is part of the citric acid cycle. Which molecule is oxidized in this reaction?

succinate

Claisen condensation

the carbanion is stabilized by the carbonyl of an adjacent thioester EX: synthesis of citrate in the citric acid cycle

Proteome

the entire set of proteins expressed by a given cell or group of cells

Acetyl-CoA has a high-energy _____ bond.

thioester

ATP is thermodynamically _____ and kinetically _____.

unstable; stable

For redox reactions using NADPH or NAD+, the metabolite concentration is usually _____ the Km.

well above

Which statement is false about adenylate kinase?

It recycles AMP to ADP during periods of intense demand for ATP.

conjugate redox pair

acceptor and donor of a half of a redox reaction

The reaction catalyzed by inorganic pyrophosphatase releases energy, driving:

adenylylation reactions.

The reaction shown can BEST be classified as a(n):

aldol condensation.

Which enzyme does NOT catalyze a free-radical reaction?

aldolase

Transcriptome

all the RNA molecules transcribed from a genome

Studies suggest that the activation of dopamine β-hydroxylase is mediated by stimulation of enzyme synthesis without altering the rate of enzyme degradation. This is an example of:

altering the number of enzyme molecules.

Which is NOT a way in which electrons are transferred from one molecule to another?

as a proton

Glycosyl transfer

attachment of sugars. Substitution with O/N nucleophile, often anomeric carbon as electrophile (group transfer reaction)

Acyl transfer

biosynthesis of fatty acids. Acyl substitution with carbonyl carbon as the electrophile (group transfer reaction)

What determines which reactions take place in biological systems?

both their relevance to that particular metabolic system and their rates

Synthases

catalyze condensation reactions in which no nucleoside triphosphate is required as an energy source

Synthetase

catalyze condensation reactions that do use ATP or another nucleotide triphosphate as an energy source

nucleophilic attack

characterized by a nucleophile attacking an electrophile

Aldol condensation

common route to the formation of a C-C bond EX: the aldolase reaction, which converts a six-carbon compound to two three-carbon compounds in glycolysis is an aldol condensation in reverse

Which process involves a group transfer from ATP or GTP rather than direct hydrolysis of ATP or GTP to ADP (or GDP) and Pi?

conversion of glutamate to glutamine

Which process involves a nucleophilic attack at the γ position of ATP?

conversion of glutamate to glutamine

Nucleophilic attack by an alcohol on the γ phosphate of ATP:

displaces ADP and produces a new phosphate ester.

Nucleophilic attack at the β phosphate of ATP:

displaces AMP and transfers a pyrophosphoryl (not pyrophosphate) group to the attacking nucleophile

Nucleophilic attack at the α position of ATP:

displaces PPi and transfers adenylate (5′-AMP) as an adenylyl group; the reaction is an adenylylation

Which is NOT a process for which heterotrophic cells use ATP?

driving exergonic reactions

Consider the reaction shown. R—CH3 + ½O2 → R—CH2—OH What is the electron donor and what is the electron acceptor in this reaction?

electron donor = hydrocarbon; electron acceptor = oxygen atom

This reaction can BEST be described as a(n):

elimination.

If for a particular equilibrium reaction A ⇌ B we find that, at equilibrium, the concentration of A is twice the concentration of B, what is ΔG′° for the reaction at 25 °C?

+1.7 kJ/mol

3-Phosphoglycerate (3PG) is an intermediate in glycolysis that is formed when a phosphate group from 1,3-BPG is transferred to ADP, forming ATP.1,3-BPG + ADP → 3PG + ATPThis reaction is reversible and, under conditions of high [ATP] and high [3PG], it will go in the reverse direction, requiring the COO− group on 3PG to attack as a nucleophile at the phosphate on ATP.ΔG′° for the reaction is −18.8 kJ/mol.Assuming an equilibrium ratio for [ATP]/[ADP] of 10,000/1, what is the ratio of [3PG]/[1,3-BPG] at 37 °C at equilibrium

0.147

Identify the order of events in the conversion of glucose 6-phosphate to fructose 6-phosphate catalyzed by phosphohexose isomerase.

1. An ionizable group on the enzyme abstracts a proton, allowing the formation of a C=C bond 2. An ionizable group on the enzyme donates a proton, allowing the formation of an O—H bond. 3. An ionizable group on the enzyme abstracts a proton, allowing the formation of a C=O bond. 4. An ionizable group on the enzyme donates a proton, allowing the formation of a C—H bond.

Which answer choice correctly identifies the order of events in a phosphoryl group transfer? 1. Departure of the leaving group 2. Formation of a relatively stable pentacovalent structure 3. Nucleophilic attack of the electrophilic phosphorus atom in ATP

3, 2, 1

The conversion of phosphoenolpyruvate to pyruvate has a K′eq value of 7 × 1010, and the formation of ATP from ADP has a K′eq value of 5 × 10−6. The last step in glycolysis is the transfer of the phosphoryl group from phosphoenolpyruvate to ADP, generating pyruvate and ATP.Phosphoenolpyruvate + ADP → pyruvate + ATPWhat is the K′eq value for the overall reaction?

3.5 × 105 (Keq1)(Keq2)=K'eq

Standard free-energy changes are:

ADDITIVE

Which does NOT provide the chemical basis for the large free-energy change associated with ATP hydrolysis?

ADP dissociates to adenosine and PPi, lowering the product concentration.

Which statement about group transfer reactions is false?

Acyl group transfer generally involves the addition of an electrophile to the carbonyl carbon of an acyl group.

Which phosphate of ATP is susceptible to nucleophilic attack?

All three phosphates are susceptible to nucleophilic attack and each position of attack yields a different type of product

How do you treat ∆G values in a biochemical pathway?

Always add them together!

Nucleoside diphosphate kinase

An enzyme that catalyzes the transfer of the terminal phosphate of a nucleoside 5'-triphosphate to a nucleoside 5'-diphosphate

This reaction can BEST be described as a(n):

Claisen condensation.

Consider these two half-reactions, both of which occur in the mitochondrial electron transfer chain, and their E′° values. ½O2 + 2H+ + 2e− → H2O E′° = 0.816 V Cytochrome c (Fe3+) + e− → cytochrome c (Fe2+) E′° = 0.254 V Which statement is true if each member of the two conjugate redox pairs is at 1 M concentration, and the system is at 25 °C and pH 7?

Electrons will flow from cytochrome c (Fe2+) to O2.

Which statement is false about phosphocreatine (creatine phosphate)?

Enzymes that use ATP, such as myosin ATPase, can hydrolyze phosphocreatine when ATP levels are low.

Proton transfer

Group transfer reaction, very common acid-base reaction

Which statement is true about nucleoside diphosphate kinase?

It catalyzes a two-step process involving a phosphoenzyme intermediate.

Which statement is false regarding the control of flux in most metabolic pathways?

It does not depend on metabolic circumstances.

Which statement is true regarding ΔG?

It is always negative for any reaction proceeding spontaneously toward its equilibrium.

In the general reaction A + B → C + D, the equilibrium constant is given by the equation:

Keq = [C][D]/[A][B].

In the reaction maltose + H2O → 2 glucose, the equilibrium constant is given by the equation:

Keq = [glucose]2/[maltose].

A chemist optimizes a chemical reaction such that product concentration exceeds the concentration of the reactants. What conclusions can be drawn about K′eq and ΔG′° in this reaction?

K′eq > 1, ΔG′° < 0

Phosphoryl transfer

MOST COMMON to activate metabolites, also important signal transduction and energy currency. Substitution with P as the electrophile (group transfer reaction)

How do you treat equilibrium constants in a biochemical pathway?

Multiply them together

Which statement is true regarding cellular concentrations of NAD and NADP?

NADPH is generally present at a higher concentration than NADP+.

Transcription factors

Nuclear proteins that regulate gene transcription within a cell.

Which statement is false about oxidation-reduction reactions?

Oxidation reactions and reduction reactions can occur either together or separately.

Which statement is false regarding niacin deficiency?

People with alcoholism benefit greatly from niacin supplements.

Which statement is true about the relationship between ΔG′° and K′eq?

Relatively small changes in ΔG′° correspond to large changes in K′eq.

Why is inorganic phosphate so stable?

Resonance

General reactions of ATP are:

SN2 nucleophilic displacements, in which the nucleophile may be the oxygen of an alcohol or carbohydrate, or a nitrogen of creatine, or of the side chain of arginine or histidine

Which statement is false about this metabolic pathway?

Step 1 has the largest net forward rate.

Which statement correctly compares or contrasts synthases and synthetases?

Synthetases require a nucleoside triphosphate, whereas synthases do not.

Which statement is false about factors affecting the translation of mRNA into protein product?

The amount of protein product is always directly proportional to the amount of mRNA in the cell.

Metabolome

The complete set of metabolic intermediates and other small molecules produced in an organism

Standard reduction potential (E°)

The electromotive force exhibited at an electrode by 1 m concentrations of a reducing agent and its oxidized form at 25 °C; a measure of the relative tendency of the reducing agent to lose electrons. E′° denotes the standard transformed reduction potential at pH 7.0 and 55.5 m water used by biochemists.

Standard reduction potential E′°

The electromotive force exhibited at an electrode by 1 m concentrations of a reducing agent and its oxidized form at 25C, a measure of the relative tendency of the reducing agent to lose electrons. *standard transformed reduction potential at pH 7.0 and 55.5 m water used by biochemists.

The E′° values for the FAD/FADH2 and fumarate/succinate conjugate redox pairs are −0.219 V and 0.031 V, respectively. Which statement accurately compares these two conjugate redox pairs?

The fumarate/succinate pair has the greater tendency to accept electrons and is therefore the stronger oxidizing system.

Which statement is true about the entropy of a growing cell?

The increase in entropy outside the cell is greater than the decrease in entropy inside the cell.

Which statement about inorganic phosphate is false?

The phosphorus atom can act as a nucleophile.

Consider a chemical reaction with an equilibrium constant of 1,000 and a standard free-energy change of −10 kJ/mol. Which statement is true about this reaction?

The products contain less free energy than the reactants, and the reaction will proceed spontaneously under standard conditions.

Mass-Action Ratio

The ratio of the product of the concentrations of reaction products to that of the reactants. -Supply and demand of a cell; dictates whether a reaction will move forward or backwards irrespective of the equilibrium constant

The reaction catalyzed by phosphofructokinase-1 (PFK-1) has a K′eq of 1.0 × 103 and a mass-action ratio (Q) in the liver of 1 × 10−1. Which statement is false about this reaction?

The reaction is endergonic under cellular conditions.

Which statement is false about the hydrolysis of phosphoenolpyruvate (PEP) to pyruvate?

The reaction occurs with a net gain in entropy.

An oxygen ester has a free energy of hydrolysis of −24 kJ/mol, while that for a thioester is −31 kJ/mol. What can be said about the acyl exchange reaction involving a free thiol and an oxygen ester?

The reaction will be nonspontaneous, but may become spontaneous at high concentrations of the thiol.

Methyl transfer

Various biosynthesis substitution with methyl carbon as the electrophile (group transfer reaction)

Which statement is false regarding ΔG′°?

When it is positive, the reaction will proceed spontaneously under standard conditions.

homolytic cleavage

When the bond breaks, each atom gets one electron

heterolytic cleavage

When the bond breaks, the most electronegative atom gets both electrons *More common than homolytic cleavage

Which statement is false regarding the nucleophilic displacement reactions of ATP?

When the γ position is the target of a nucleophilic attack, ADP is displaced and a phosphate group is transferred to the nucleophile.

When ATP is hydrolyzed at a pH above 8.5 in the absence of Mg2+, the chemical reaction is represented by ATP4− + H2O → ADP3− + HPO2−4 + H+ The corresponding equilibrium constant depends on all of these EXCEPT for:

[H2O].

Consider these data in the table. Which reaction should be spontaneous under standard conditions?

glucose 3-phosphate + Pi → glucose + PPi

Which does NOT help explain the difference in the actual free energy of ATP hydrolysis in living cells compared with the standard free-energy change of ATP hydrolysis?

intracellular [H2O]

In the course of evolution, organisms have acquired a remarkable collection of regulatory mechanisms for maintaining homeostasis at the _____ level(s).

molecular, cellular, and organismal

An enzyme that displays no cooperativity has a Hill coefficient equal to:

one.

A positive E′° value means that the _____ member of a conjugate pair _____ to accept electrons.

oxidized; tends

All enzymes are sensitive to the concentration of their substrate(s). A Km value defines the concentration of substrate when an enzyme is at

½Vmax.

Which equation correctly relates changes in free energy, enthalpy, and entropy?

ΔG = ΔH − TΔS

What would happen if the reaction ATP → ADP + Pi were allowed to approach equilibrium in the cell?

ΔGp would approach zero, and ATP would lose the high phosphoryl group transfer potential that makes it valuable to the cell.