RX312 Exam 3

What is the body's energy currency?

ATP

What has the lowest level of energy release of hydrolysis?

PEP (phosphoenolpyruvate)

What cofactor is prevalent in catabolic reaction?

NADPH

What cofactor is prevalent in anabolic reaction?

NADP

What is the fate of glucose?

1. Polymerization - mechanism of Storage (Glycogen, starch, sucrose) 2. Oxidation via glycolysis (pyruvate) 3. Oxidation via pentose phosphate pathway (Ribose 5-phosphate)

What is used in biosynthetic reactions?

NADPH

What is linked to the homeostasis of glucose?

The Liver

Muscles lake what?

phosphatase

What happens to glucose in the muscle?

It stays in the muscle because there are no phosphatases

Transketolase is part of what mechanism?

What happens to pyruvate in the presence of oxygen?

pyruvate is transformed into an acetyl group attached to a carrier molecule of coenzyme A. The acetyl group is delivered to the citric acid cycle for further catabolism.

What is TAG?

What is the reverse pathway of glycolysis?

Gluconeogenesis

Lactate

Lactic acid

What happens to pyruvate in the absence of oxygen?

NADH + H+ from glycolysis will be recycled back to NAD+ so that glycolysis can continue

Lactate can be exported into the blood, which can cause what?

decrease pH in the blood. Bicarbonate will try to counteract this.

What are the two phases of glycolysis?

1. Investment phase 2. Energy payoff phase

Phosphorylation is involved in metabolite formation and signaling, but what is different?

Different enzymes

What is the enzyme that causes phsphorylation in metabolism?

Hexokinase

Phosphofructokinase is found where?

Step 3 in glycolysis

F26BP

allosteric regulator of glycolysis and gluconeogenesis

F26BP affects glycolysis by...

activating it

F26BP affects gluconeogenesis by...

inhibiting it

Catabolic pathways relate to a(n) ____of free energy and anabolic pathways to a(n) ______ of free energy.

A. input; input B. input; release C. release; input D. release; release

C. release; input

What is pyruvate?

A. The end product of glycolysis B. The precursor of alanine C. Can be converted to acetyl-CoA D. Can be carboxylated to form the precursor for other amino acids E. All of the above

E. All of the above

Which of the compounds below is in the highest oxidation state?

A. Carbon monoxide B. Methane C. Methanol D. Carbon dioxide E. Acetic acid

D. Carbon dioxide

What cofactor would be needed to carry out the first reaction of the first step in the anabolic pentose phosphate pathway?

A. NADP+ B. NADH C. NADPH D. FADH2

A. NADP+

What molecule has the highest change in free energy in the process of dephosphorylation?

A. Phosphoenolpyruvate B. CTP C. ATP D. Glucose-6-phosphate

A. Phosphoenolpyruvate

Consider the following metabolic retain in the tricarboxylic acid cycle: Succinyl-CoA + Acetoacetate ==> Acetoacetyl-CoA + Succinate DeltaG°' = -1.25 kJ/mol What statement is true:

A. Favorable in the direction indicated under metabolic conditions B. Unfavorable in the direction indicated under standard conditions C. At equilibrium

A. Favorable in the direction indicated under metabolic conditions

What is a characteristic of regulatory steps of a metabolic pathway?

A. A step that functions near equilibrium and has a large positive free energy change B. A step that functions near equilibrium and has a large negative free energy change C. A step that functions far from equilibrium and has a large positive free energy change D. A step that functions far from equilibrium and has a large negative free energy change

D. A step that functions far from equilibrium and has a large negative free energy change

What is NOT a fate for glucose?

A. Ribose-5-phosphate B. Pyruvate C. Glycogen D. NADPH

D. NADPH

What strategy is used to generate ATP in glycolysis?

A. Phosphorylation B. Isomerization C. Glycosylation D. Hydrolysis

A. Phosphorylation

Which of the mechanisms described below can be used to drive the reaction A + B -> C + D > ΔG = +13kJ/mol A. Deplete the concentration of substrate B B. Reduce the enthalpy of the substrate A C. Deplete the concentration of the product D D. Reduce the enthalpy of the product C

C. Deplete the concentration of the product D

Catabolic pathways for biomolecules such as proteins, and fatty acids converge on which fundamental metabolite?

A. NADH B. Acetyl-CoA C. ATP D. Glucose

B. Acetyl-CoA

How do electrostatic interactions contribute to the free energy of hydrolysis of ATP?

A. Electrostatic attraction destabilizes ATP, and therefore makes hydrolysis favorable B. Electrostatic repulsion destabilizes ATP, and therefore makes hydrolysis favorable C. Electrostatic interactions have little effect since ATP, ADP and Pi are all negatively charged D. Electrostatic repulsion stabilizes ATP, and therefore makes hydrolysis less favorable

B. Electrostatic repulsion destabilizes ATP, and therefore makes hydrolysis favorable

What is the difference between Catabolism and Anabolism?

A. Anabolism consumes ATP while catabolism generates ATP B. Catabolism involves breakdown of complex biomolecules into smaller metabolites for the purpose of energy generation and biosynthesis and

Anabolism is the biosynthesis of complex biopolymers from smaller metabolites C. Catabolism is an enzymatic process while Anabolism is not D. Catabolism is the biosynthesis of complex polymers and Anabolism is the breakdown of polymers into small metabolites

B. Catabolism involves breakdown of complex biomolecules into smaller metabolites for the purpose of energy generation and biosynthesis and Anabolism is the biosynthesis of complex biopolymers from smaller metabolites

What molecule is considered an electron carrier during anabolism?

A. NADH B. ATP C. NADPH D. Glucose

C. NADPH

Which of the following is always involved in biological oxidation-reduction reactions?

A. Oxygen B. Transfer of phosphate C. Transfer of electron(s) D. Formation of water

C. Transfer of electron(s)

What are the potential control points in glycolysis? The numbers refer to the glycolysis reaction steps.

A. Possible 1, 4, 9: Actual: 1 B. Potential 1, 3, 10; Actual: 3 C. Possible: 1, 3, 10; Actual : 1 D. Possible: 2, 3, 9; Actual 2

B. Potential 1, 3, 10; Actual: 3

In a metabolic pathway, the reactions that control flux through the pathway

A. have large positive free energy changes. B. can operate in the forward or reverse direction. C. are close to equilibrium. D. catalyze irreversible reactions.

D. catalyze irreversible reactions.

Glucose-6-phosphate is a substrate or product for which of the following metabolic processes?

A. All process or pathways listed B. Glycolysis C. Pentose Phosphate pathway D. Glycogenolysis

A. All process or pathways listed

What is a major allosteric regulator of glycolysis at the rate-limiting step?

A. fructose-1,6-bisphosphate B. 2,3-bisphosphoglycerate C. fructose-2,6-bisphosphate D. 1,3-bisphosphoglycerate

C. fructose-2,6-bisphosphate

A key strategy in glycogen synthesis is the generation of what intermediate between glucose-1-phosphate and glycogen?

A. glucose-1,6-bisphosphate B. Glucose-6-phosphate C. Glucose D. UDP-glucose

D. UDP-glucose

What metabolites does glycogen synthesis and glycogen breakdown share?

A. ADP-Glucose B. Glucose-6-phosphatase C. UDP-Glucose D. Glucose-1-phosphate

D. Glucose-1-phosphate

What key cofactor is generated in the oxidative reactions of the pentose phosphate pathway?

A. NADH B. FADH2 C. NAD+ D. NADPH E. NADP+

D. NADPH

Which step is key to the regulation of gluconeogenesis?

A. pyruvate kinase B. fructose bisphosphatase C. pyruvate carboxylase D. hexokinase

B. fructose bisphosphatase

What is the consequence of the inhibition of pyruvate kinase to gluconeogenesis?

A. Accumulation of phosphoenolpyruvate and glyceraldehyde B. Increase in levels of AMP C. No effect D. Depletion of pyruvate

C. No effect

A liver biopsy of a four-year-old boy indicated that the fructose-1,6-bisphosphatase enzyme activity was 20% of normal. The patient's blood glucose levels were normal at the beginning of a fast but then decreased suddenly. Why is the blood glucose level normal at the beginning of the fasting period?

A. blood glucose levels is being maintained by lactate B. blood glucose levels is being maintained by pyruvate C. blood glucose level is being maintained by the glycogen store D. blood glucose levels is being maintained by glyceraldehyde-3phosphate

C. blood glucose level is being maintained by the glycogen store

Which of the following metabolites can serve as a source of carbon for gluconeogenesis?

A. proteins B. lactate C. glycerol D. all of the options listed

D. all of the options listed

Which pathway(s) provides the precursor to the ribose component of nucleotides?

A. Glycolysis B. Pentose phosphate pathway (PPP) C. Glycogenolysis D. TCA

B. Pentose phosphate pathway (PPP)

Except during starvation, the brain burns glucose as its sole metabolic fuel, yet stores very little glucose as glycogen. Based on this information, what is the major control point in glycolysis as it operates in brain cells?

A. phosphofructosekinase B. aldolase C. pyruvate kinase D. hexokinase

D. hexokinase

A reaction that results in the loss of electrons from a molecule is a(n) _____.

A. oxidation B. reduction C. hydrolysis D. ligation E. phosphorolysis

A. oxidation

What pathway is used to make glucose from other metabolites such as oxaloacetate?

A. pentose phosphate pathway B. glycogen synthesis C. glycolysis D. gluconeogenesis

D. gluconeogenesis

One enzyme of the glycolytic pathway is regulated by feed forward activation. Which of the following pairs listed below gives the correct enzyme and the regulatory intermediate?

A. pyruvate kinase (enzymes); fructose 1,6-bisphosphate (metabolite) B. glyceraldehyde 3-phosphate dehydrogenase (enzyme); fructose 6-phosphate (metabolite) C. hexokinase(enzymes); 2-phosphoglycerate(metabolite) D. phosphofructokinase (enzyme); glucose 6-phosphate (metabolite) E. phosphoglycerate kinase(enzyme); fructose 2,6-bisphosphate (metabolite)

A. pyruvate kinase (enzymes); fructose 1,6-bisphosphate (metabolite)

The process of _____ converts glucose into _____.

A. glycolysis; pyruvate B. glycogen synthesis; pyruvate C. gluconeogenesis; glycogen D. glycogenolysis; glycogen

B. glycogen synthesis; pyruvate

What is the net equation of glycolysis as it occurs in aerobic cells such as brain cells?

A. Glucose + 2 ADP + 2 Pi + 2 NAD+ → 2 lactate + 2 ATP + 2 NADH + 4 H+ B. Glucose + 2 ADP + 2 Pi → 2 CH3CH2OH + 2 CO2 + 2 ATP C. Glucose + 2 ADP + 2 Pi + 2 NAD+ → 2 pyruvate + 2 ATP + 2 NADH + 4 H+ D. Glucose + 2 ATP → 2 lactate + 2 ADP + 2 Pi

C. Glucose + 2 ADP + 2 Pi + 2 NAD+ → 2 pyruvate + 2 ATP + 2 NADH + 4 H+

Which of the following is more oxidized than acetaldehyde?

A. ethanol B. ethane C. ethylene glycol D. acetic acid

D. acetic acid

What are the coenzyme forms that correspond to X and Y in the following reaction? 1,3-bisphosphoglycerate + X → glyceraldehyde-3-phosphate + Pi + Y

A. X = NADPH + H+, Y = NADP+ B. X = NAD+, Y = NADH + H+ C. X = NADH + H+, Y = NAD+ D. X = FAD, Y = FADH2

C. X = NADH + H+, Y = NAD+

Brazilin, a compound found in aqueous extracts of sappan wood, has been used to treat diabetics in Korea. Brazilin increases the activity of the kinase enzyme that produces F26BP and the compound also stimulates the activity of pyruvate kinase. What is the effect of adding brazilin to hepatocytes (liver cells) in culture?

A. stimulate gluconeogenesis B. stimulates glycolysis C. Stimulates glucose biosynthesis D. stimulates glycogenolysis

B. stimulates glycolysis

Gluconeogenesis is most active in what organ?

A. brain B. kidneys C. heart D. muscles E. liver

E. liver

The pyruvate → acetyl-CoA reaction can proceed only in the direction indicated (irreversdibly). Given this limitation, consult Figure 12.9 and tell which of the following transformations are possible: a. acetyl-CoA → glucose, b. acetyl-CoA → fatty acids, c. acetyl-CoA → alanine.

b. acetyl-CoA → fatty acids

For the reaction E ⇌ F, Keq = 1. a. Without doing any calculations, what can you conclude about the ∆G°′ value for the reaction? b. You place 1 mM F in a tube and allow the reaction to reach equilibrium. Determine the final concentrations of E and F.

DeltaG = -RT ln(ratio == (Keq) A +B

One can envisage two mechanisms for coupling ATP hydrolysis to the phosphorylation of fructose-6-phosphate (F6P) to fructose-1,6-bisphosphate (F16BP) (see Problem 81), yielding the same overall reaction: I: ATP is hydrolyzed as F6P is transformed to F16BP:(F6P + Pi ⇌ F16BP + H2O)(ATP + H2O ⇌ ADP + Pi) II: ATP transfers its γ phosphate directly to F6P in one step, producing F16B (F6P + ATP ⇌ F16BP + ADP) Choose one of the above mechanisms as the more biochemically feasible and provide a rationale for your choice.

Coupling helps to select the more biochemically feasible. Therefore, Mechanism I is more favorable. The direct process is not favorable in Mechanism II. Breaking down the steps, the more favorable it is. More steps means that it is more favorable.

Glyceraldehyde-3-phosphate (GAP) is converted to 3-phosphoglycerate (3PG) in one of the steps in the glycolytic pathway. Consider these two scenarios: I. GAP is oxidized to 1,3-BPG (∆G°′ = 6.7 kJ · mol−1), which is subsequently hydrolyzed to yield 3PG (∆G°′ = −49.3 kJ · mol−1). II. GAP is oxidized to 1,3-BPG, which subsequently transfers its phosphate to ADP, yielding ATP (∆G°′ = −18.8 kJ · mol−1). Which is more likely to occur in the cell, and why?

Scenario II is more likely to occur in the cell because deltaG is smaller which allows for a reversible reaction.

Researchers isolated a yeast phosphofructokinase mutant in which a serine at the fructose-2,6-bisphosphate (F26BP) binding site was replaced with an aspartate residue. The amino acid substitution completely abolished the binding of F26BP to PFK. There was a dramatic decline in glucose consumption and ethanol production in the mutant compared to control yeast. a. Propose a hypothesis that explains why the mutant PFK cannot bind F26BP. b. What does the decline of glucose consumption and ethanol production in the yeast reveal about the role of F26BP in glycolysis?

a. I would expect F26BP to bind allosterically to PFK, possibly with a phosphate group H-bonding to the serine. If the serine is replaced with the negatively charged aspartate, the negative charges on F26BP are repelled by it, and F26BP cannot bind to the enzyme. The stimulation is gone and there is a decline in consumption and production of ethanol. b. It is an essential role.

Vanadate, inhibits GAPDH, not by acting as a phosphate analog, but by interacting with essential —SH groups on the enzyme. What happens to cellular levels of phosphate, ATP, and 2,3-bisphosphoglycerate (see pathway below) when red blood cells are incubated with vanadate?

Cellular levels of phosphate will increase, ATP will decrease, and 2,3-biphosphoglycerate will decrease

The concentration of fructose-2,6-bisphosphate (F26BP) is regulated in the cell by a homodimeric enzyme with two catalytic activities: a kinase that phosphorylates fructose-6-phosphate to form F26BP and a phosphatase that catalyzes the hydrolysis of the C2 phosphate group.

a. Which enzyme activity, the kinase or the phosphatase, would you expect to be active under fasting conditions? Explain. b. Which hormone is likely to be responsible for inducing this activity? c. Consult Section 10.2 and propose a mechanism for this induction. a. The phosphatase activity is active under fasting conditions. The phosphatase removes the phosphate group from F26BP, forming fructose-6-phosphate. Thus F26BP is not present to stimulate glycolysis (or to inhibit glucogenesis). Therefore, gluconeogenesis is active. The body is trying to maintain glucose levels, and synthesis is stimulated. b. The hormone of the fasted state is glucagon c. When glucagon binds to its receptors, cellular cAMP levels rise. This activates protein kinase A, which phosphorylates the bifunctional enzyme, resulting in the activation of the phosphatase activity and the inhibition of the kinase activity

In addition to phosphorylating glycogen phosphorylase, glucagon signaling results in the phosphorylation of glycogen synthase. Is the phosphorylated form of the enzyme active or inactive? Propose a signaling mechanism through G-protein coupled receptors

Glycogen synthase is inactive when it is phosphorylated. When bound to cAMP, protein kinase A (PKA) phosphorylates and inactivates the glycogen synthase enzyme. The activity of protein phosphorylase 1 (PP1) is required to dephosphorylate GS and restore its activity.

What drives reactions?

the cleavage of ATP

Type of reaction fundamental to metabolism

oxidation and reduction reactions

anabolic

catabolic

oxidation

reduction

Anabolic =

making

Catabolic =

destroying

NADP+ or NADPH: Anabolic

NADPH

NADP+ or NADPH: Catabolic

NADP+

Anabolic electrons

passing up electrons

Catabolic electrons

passing down electrons

NADPH

NADP+

NADH

NAD+

What is the reductant in anabolic (synthetic) reactions?

NAD(P)H

What as in example of where NAD(P)H used?

Fatty acid synthesis

What is an example of an electron acceptor?

NAD(P)+

WHat reaction is NAD(P)+ used in?

catabolic

What are some examples of most reduced forms of carbons?

Metabolic fuel (reduced) loses an electron and becomes what?

metabolic fuel (oxidized)

Cofactor (oxidized) gains an electron and becomes what?

cofactor (reduced)

Synthesis of ATP is driven by what?

chemical gradient

Catabolic reactions are...

• passing electrons down - carbs, fats, proteins into CO2, H2O, NH3 - ADP+ to ATP

NADP+ to NADPH

What is the currency of energy in the body?

ATP

Chemical reaction types

• Oxidoreductase - transferase - hydrolase

Oxidoreductase

• NADP is used: Catabolism - NADPH is used: Anabolism

Transferase

phosphate transfer