3: Carbohydrate Metabolism

Explain the steps by which adrenaline injection determines a rise in blood glucose

1. Activation of the adrenaline β-receptor in liver

2. Activation of adenylate cyclase through G-protein

3. Formation of cAMP

4. Activation of PKA (by dissociation of catalytic subunits)

5. Phosphorylation and activation of phosphorylase b kinase

6. Phosphorylation and activation of phosphorylase b to phosphorylase a

7. Glycogenolysis with formation of glucose-1-P

8. Isomerization of G1P to glucose-6-P

9. Hydrolysis by glucose-6-phosphatase of Glucose-6-P to free glucose

10. Export of glucose to blood by GLUT2

Cortisone treatment may induce diabetes because

• a) Cortisone activates glycogenolysis in muscle

• b) Cortisone activates gluconeogenesis

• c) Cortisone inhibits muscle hexokinase

• d) Cortisone inhibits glucose-6-phosphatase

b) Cortisone activates gluconeogenesis

Cortisone (like the physiological hormone cortisol) stimulates gluconeogenesis through induction in liver of glucogenetic enzymes. The newly synthesized glucose is mostly released in the blood stream with consequent hyperglycaemia.

a) Glycogenolysis in muscle cannot affect blood glucose because glucose-6-phosphatase is absent in muscle.

Which of the following you expect if you observe an increase of fructose-2,6-bisphosphate?

• a) An increase of cyclic AMP

• b) Increased glycemia

• c) Enhanced formation of ATP by glycolysis

• d) Enhanced gluconeogenesis

c) Enhanced formation of ATP by glycolysis

a) False. It is synthesized through the action of insulin, so cAMP must be low.

b) False. Enhanced glycolysis consumes glucose, therefore glycemia decreases

c) True. Fructose-2,6-bisphosphate is an allosteric activator of phosphofructokinase-1 and therefore activates glycolysis.

d) False. Fructose-2,6-bisphosphate inhibits gluconeogenesis (fructose 1,6 bisP phosphatase), preventing the reaction F-1,6-BP → F6P

ΔG’° of the aldolase reaction in glycolysis = +23.8 kJ/mol

fructose-1,6-bisP → glyceraldehyde-3-P + dihydroxyacetone-P

Nevertheless, the reaction takes place without difficulty. The reason is:

• a) The reaction is coupled to ATP hydrolysis

• b) The concentrations of reactants and products at steady state determine a favourable negative ΔG

• c) Glyceraldehyde-3-P and dihydroxyacetone P can be isomerized into one another

• d) Fructose-1,6-bisP is a high-energy compound

b) The concentrations of reactants and products at steady state determine a favourable negative ΔG

In glycolysis, the concentration of fructose-1,6-bisphosphate (reactant) is kept high. Concentrations of glyceraldehyde-3-P and dihydroxyacetone-P (products) are kept low because they’re rapidly used up in downstream steps.

This shifts the reaction equilibrium toward the products → making ΔG negative in vivo.

Calculate the ΔG of the aldolase reaction (ΔG’° = + 23.8 kJ/mol) at the following concentrations of FBP, GAP and DOP, respectively:

1. 0.01 M, 0.01 M, 0.01 M

2. 1 mM , 1 mM, 1 mM

3. 0.1 mM, 0.1 mM, 0.1 mM

4. 10 µM, 10 µM, 10 µM

FBP → GAP + DOP

ΔG = ΔG’° + 6 log [DOP][GAP]/[FBP]. (For calculation, express all data in M units)

1. ΔG = 23.8 + 6 (-2) = + 11.8

2. ΔG = 23.8 + 6 (-3) = + 5.8

3. ΔG = 23.8 + 6 (-4) = - 0.2

4. ΔG = 23.8 + 6 (-5) = - 6.2

During its lifetime one molecule of cAMP is able to activate 100 molecules of PKA. If each of the further steps has the same yield, calculate how many molecules of glucose-1-P are formed. Explain the individual steps.

1 cAMP → 100 molecules PKA

1 PKA → 100 molecules phosphorylase b kinase

1 phosphorylase b kinase → 100 molecules of phosphorylase b to phosphorylase a

1 active phosphorylase a → 100 molecules of glucose-1-P

Thus 100×100×100×100= 10⁸ molecules of glucose-1-P

Which of the following you expect may contribute to elevate glycaemia?

• a) Glycolysis

• b) Glycogenolysis

• c) Glucokinase reaction

• d) Pentose phosphate shunt

Only b) Glycogenolysis is correct. The other pathways or reactions consume glucose and therefore remove it from the blood.

Explain the rationale of the allosteric regulation of pyruvate kinase: activation by fructose-1,6-bisphosphate and inhibition by acetyl CoA and ATP

• Pyruvate kinase is the last reaction of glycolysis, yielding pyruvate and ATP from phosphoenolpyruvate and ADP

• The activation by fructose-1,6-bisP represents a kind of feed-forward activation: accumulation of a glycolytic intermediate stimulates its removal by activating glycolysis downhill.

• The inhibition by ATP is logical, since ATP is a product of the reaction: high energy availability would slow down energy production by glycolysis.

• Finally, acetyl CoA is the product of further oxidation of pyruvate, thus its accumulation indicates that oxidative metabolism must be slowed down.

The following statements refer to ATP. Only one is true.

• a) Is needed for glycogen synthesis

• b) Activates glycogenolysis

• c) Activates glycolysis

• d) Is synthesized during glycogenolysis

a) True. The direct energy donor for glycogen synthesis is UTP with formation of UDPG and then UDP. However UTP must be regenerated from UDP by means of nucleoside diphosphate kinase (UDP + ATP → UTP + ADP)

b) False. ATP inhibits glycogenolysis in muscle

c) False. ATP is an allosteric inhibitor of phosphofructokinase and therefore inhibits glycolysis

d) False

There are many cases of genetic disease in which one or another enzyme activity is lacking due to genetic mutation. However, cases in which individuals lack one of the enzyme activities of the citric acid cycle are very rare. Why?

The TCA cycle is so vital for aerobic cells that any mutation would be lethal and will not allow formation and life of the embryo.

In the citric acid cycle oxidations, O₂ does not participate directly in any reaction.

1. Where does the oxygen added to substrates in the cycle come from?

2. Where do electrons from substrates oxidized go?

3. Why is O₂ required for the citric acid cycle to proceed at reasonable rate in aerobic organisms?

In the TCA cycle there are 4 oxidation steps (3 reduce NAD+ to NADH, one reduces CoQ via enzyme-bound FAD).

1. It comes from H₂O (1 molecule in citrate synthase reaction, 1 molecule in fumarase reaction and 1 molecule from condensation of GDP and P_i in substrate-level phosphorylation)

GDP-H + P-OH + succinyl CoA → GTP + succinate  + CoASH

2. Electrons go to reduce coenzymes feeding the respiratory chain

3. In absence of oxygen, the respiratory chain remains in the reduced state and NADH accumulates; 3 Krebs cycle oxidations require NAD⁺ in oxidized form. If NADH cannot be reoxidised, the Krebs cycle oxidations cannot take place and the whole cycle stops

Is the malate/aspartate shuttle a cyclic pathway? If so, name a molecular support and a product (e.g. in the urea cycle the support is ornithine and the product is urea)

Yes.

Support = oxaloacetate reduced by glycolytic NADH and regenerated at the end of the cycle

Net product = mitochondrial hydrogen atoms in the form of mitochondrial NADH that is oxidized in the respiratory chain

Construct a scheme containing the following terms:

• 1,3-bisphosphoglycerate

• Coenzyme Q

• dihyroxyacetone phosphate

• glyceraldehyde-3-P

• glyceraldehyde-3-P dehydrogenase

• glycerol-3-P

• glycerol-3-P dehydrogenase

• inner mitochondrial membrane

• NAD+

• NADH

• outer mitochondrial membrane

Some terms may be repeated more than once.

The scheme refers to the glycerol phosphate shuttle

C₂ of glucose will be found

• a) In CO₂

• b) In the thioester C of acetyl CoA

• c) In methyl C of acetyl CoA

• d) In all of them

• e) In none of them

b) In the thioester C of acetyl CoA

C₂ corresponds to the keto group of pyruvic acid

C₃ of glucose will be found

• a) In CO₂

• b) In the thioester C of acetyl CoA

• c) In methyl C of acetyl CoA

• d) In all of them

• e) In none of them

a) In CO₂

C₃ will correspond to the carboxyl group of pyruvic acid and will be found as CO₂

Would oxidation of pyruvate or of ethanol release more energy?

Pyruvate → acetyl CoA reduces 1 NAD⁺ to NADH that is re-oxidized in the respiratory chain (2.5 ATP). Acetyl CoA in TCA cycle gives 10 ATP. Total = 12.5 ATP

Ethanol → acetaldehyde reduces 1 NAD⁺ to NADH. Acetaldehyde → acetate reduces another NAD⁺ to NADH. Total: 2 NADH re-oxidized in the respiratory chain (5 ATP).

• Acetate is activated to acetyl CoA using ATP (2 high energy bonds since it is a pyrophosphoric cleavage). Acetyl CoA in the TCA cycle gives 10 more ATP. Total = 5-2+10 = 13 ATP.

In theory, ethanol should yield more energy since it is more reduced than pyruvate, however energy is wasted to activate acetate.

______ in muscle may be regulated in several ways. First, ______ is an ______ enzyme that is activated by ______ and inhibited by ______. Second, ______ may be activated by ______ that is released by ______ during muscle contraction. Finally the whole activation pathway may be operative after stimulation of ______ and formation of ______

Fill in the blanks using the following:

• adrenaline β receptor

• allosteric

• AMP

• ATP

• Ca²⁺

• cAMP

• glycogenolysis

• glycogen phosphorylase

• phosphorylase b kinase

• sarcoplasmic reticulum

Glycogenolysis in muscle may be regulated in several ways. First, glycogen phosphorylase is an allosteric enzyme that is activated by AMP and is inhibited by ATP. Second, phosphorylase b kinase may be activated by Ca²⁺ that is released by sarcoplasmic reticulum during muscle contraction. Finally the whole activation pathway may be operative after stimulation of adrenaline β receptor and formation of cAMP.

Only one answer is wrong. Pyruvate carboxylase

    a. is present in both mitochondria and cytosol

    b. has covalently bound biotin as prosthetic group

    c. is activated by acetyl CoA

    d. requires ATP

    e. catalyzes an anaplerotic reaction

(a) is incorrect: pyruvate carboxylase is a mitochondrial enzyme.

(b) Like other carboxylases, it has enzyme-bound biotin as prosthetic group (biocytin).

(c) It is an allosteric enzyme activated by acetyl CoA: accumulation of acetyl CoA activates the enzyme, thus supporting the TCA cycle (anaplerotic reaction, (e)).

(d) ATP is required for biotin carboxylation.

Thiamine pyrophosphate is the prosthetic group of E1 in oxidative decarboxylation of pyruvate and of transketolase. What is common in the mechanism of these reactions?

Thiamine PP catalyses the nucleophilic attack of keto groups with cleavage of the adjacent bond.

• In pyruvate dehydrogenase, TPP bound to E₁ attacks the keto group of pyruvate and releases CO₂

• In transketolase, it attacks the keto group of xylulose-5-P with transfer of the group CO-CH₂OH to ribose-5-P and release of glyceraldehyde-3-P

Lipoic acid

• a) is a water-soluble Vitamin of the B group

• b) is covalently bound to the enzyme E₃ of pyruvate dehydrogenase complex

• c) is a fatty acid having 16 carbon atoms

• d) has two sulfhydryl groups

d) has two sulfhydryl groups

a) False. It is not a vitamin

b) False. It is bound to E₂

c) False. It is a fatty acid derivative with 8 carbon atoms.

d) True. At C₁ and C₃

Concerning pyruvate dehydrogenase

• a) it is a multienzyme complex

• b) it is located in the inner mitochondrial membrane

• c) it is inhibited by CoA

• d) FAD reduced in E₃ donates electrons to CoQ bypassing Complex I

a) it is a multienzyme complex

a) True

b) False. It is in the matrix

c) False. It is inhibited by product acetyl CoA

d) False. FAD reduced in E₃ donates electrons to NAD and the resulting NADH is oxidized by Complex I.

Only one answer is incorrect. Coenzyme A

• a) is a substrate of the pyruvate dehydrogenase reaction

• b) derives from a water-soluble Vitamin

• c) has two SH groups

• d) forms a thioester bond with organic acids

c) has two SH groups

a) True

b) True. From pantothenic acid

c) False. It has one SH group

d) True. It forms thioesters with organic acids

A 20-year old boy refers pain to the legs and cramps during exercise. He has always suffered of muscle weakness, but symptoms worsened when the boy decided to do sport training. By ceasing physical activity the pain disappears in 15-30 min. It was found that glycaemia decreased during activity, but unexpectedly also blood lactate decreased even during cramps. Can you localize the enzymatic damage?

The disease is presumably due to lack of muscle glycogen phosphorylase (McArdle disease). Skeletal muscle cannot use endogenous glycogen and use glucose supply from blood; the slow rate of glycolysis does not allow formation of lactate.

In which of the following diseases you would expect hypoglycaemia at rest? More than one answer may be correct

• a) Von Gierke (lack of liver glucose-6-phosphatase)

• b) McArdle (lack of muscle glycogen phosphorylase)

• c) Hers (lack of liver glycogen phosphorylase)

• d) Tarui (lack of muscle phosphofructokinase)

In a) and c) since the supply of glucose from liver to blood is exhausted

Which of these treatments may induce hyperglycaemia?

• a) Activation of cAMP phosphodiesterase

• b) Inhibition of adrenaline β-receptors

• c) phosphorylation of glycogen phosphorylase

• d) de-phosphorylation of phosphorylase b kinase

• e) phosphorylation of GSK3

c) phosphorylation of glycogen phosphorylase

a) False. Increased cAMP degradation would decrease the breakdown of glycogen

b) False. Inhibition of adrenaline β-receptors would slow down liver glycogenolysis

c) True. Phosphorylated glycogen phosphorylase is the active form of the enzyme

d) False. The enzyme would be inactivated and glycogenolysis would stop

e) False. Insulin-dependent phosphorylation of GSK3 prevents phosphorylation of glycogen synthase keeping it active in glycogen synthesis

One answer is incorrect. An increase of blood lactate may derive from

• a) a genetic disease affecting the mitochondrial respiratory chain

• b) inhibition of lactate dehydrogenase

• c) inhibition of pyruvate dehydrogenase

• d) thiamine deficiency

• e) hypoxia

b) inhibition of lactate dehydrogenase

Lactate will accumulate in conditions preventing further oxidation of pyruvate.

a) True. Oxidative phosphorylation is impaired, leading to increased lactate

b) False. It would prevent the conversion of pyruvate to lactate

c) True. Pyruvate accumulates

d) True. TPP is required for pyruvate dehydrogenase

e) True. Leads to increased lactate due to reliance on anaerobic glycolysis

UTP is an alternative substrate for phosphofructokinase, but does not exert allosteric inhibition. Draw a substrate dependence curve with ATP and with UTP (at constant levels of fructose-6-P)

• ATP is substrate but also an allosteric inhibitor. Thus, at low concentration, ATP acts as substrate but at high concentrations it reacts with the allosteric site and exerts inhibition.

• UTP may act as substrate but has no affinity for the allosteric site, so it follows Michaelis-Menten kinetics

The reaction catalysed by glyceraldehyde-P dehydrogenase has ΔG’° = 6.3 kJ/mol, nevertheless the product 1,3-bisphosphoglycerate has a high-energy bond (ΔG’° of hydrolysis = -49.3 kJ/mol). Where does this energy come from?

• The oxidation of glyceraldehyde-3-P by NAD⁺ is a very exergonic process. The enzyme catalyses the incorporation of phosphate into the oxidation product to form a anhydride bond of 1,3-bisphosphoglycerate.

• Thus, the high energy of hydrolysis of 1,3-bisP-glycerate derives from the oxidation reaction. Part of the energy released by oxidation is conserved as a high-energy bond with phosphate.

Write the reactions that take place in the oxidation of glycerol to pyruvate and show a complete energy balance

Glycerol + ATP → glycerol-P + ADP

Glycerol-P + NAD⁺ → Dioxyacetone-P + NADH + H+

Dioxyacetone-P → Glyceraldehyde-3-P

Glyecraldehyde-3-P + NAD⁺ + Pi → 1,3-bisP-glycerate + NADH + H⁺

1,3-bisP-glycerate + ADP → 3P-glycerate + ATP

3-P-glycerate → → → P-enol-pyruvate

P-enol-pyruvate + ADP → pyruvate + ATP

ATP yield:

At substrate level: (2 - 1) = 1 ATP

Re-oxidation of 2 NADH (malate/aspartate shuttle) = 2.5×2 = 5 ATP 

Arsenate can be considered an uncoupler of glycolysis since it substitutes phosphate in the glyceraldehyde phosphate dehydrogenase reaction forming a compound that is rapidly hydrolyzed to arsenate and 3-P-glycerate. Explain the energetic consequences.

Arsenate prevents the formation of the high-energy bond with phosphate, thus impeding the synthesis of ATP by substrate-level phosphorylation (phosphoglyceryl kinase reaction)

Phosphofructokinase (PFK) is the rate-limiting step of glycolysis. If in a cell extract we double the concentration of PFK

1. Under saturating conditions of substrates, will the rate of PFK double or not?

2. Will the overall rate of glycolysis increase?

3. Will the K_m for fructose-6-P change?

4. Will we need more [fructose-6-P] to reach v_max?

1. Yes. V ∝ [E]

2. Yes, since PFK is the rate-limiting step of glycolysis

3. No. The K_m is a constant independent on enzyme concentration

4. No. The concentration of enzyme is usually much lower than that of substrate, so altering enzyme concentration will not affect substrate dependence

What is the reaction to produce UDPG?

• a) UDP + glucose

• b) UTP + glucose

• c) UTP + glucose-6-P

• d) UTP + glucose-1-P

d) UTP + glucose-1-P

Which of the following reactions requires inorganic phosphate? More than one answer may apply

• a) Phosphoglucomutase

• b) Glycogen phosphorylase

• c) Glucose-6-phosphatase

• d) Glyceraldehyde-P dehydrogenase

• e) Enolase

• f) Pyruvate kinase

b) Glycogen phosphorylase, d) Glyceraldehyde-P dehydrogenase

Muscle phosphorylase is activated by AMP. How is AMP mainly produced in muscle?

• a) During muscle contraction ATP is cleaved to AMP and PP_i

• b) ADP produced after contraction is converted to AMP by myokinase

• c) Cyclic AMP is hydrolyzed to AMP

• d) An ADPase converts ADP to AMP

b) ADP produced after contraction is converted to AMP by myokinase

a) False. ATP is cleaved to ADP and P_i

b) True

c) False. cAMP is hydrolysed to AMP by a specific phosphodiesterase, but the contribution of this reaction to muscle [AMP] is negligible.

d) No ADPase exists

In phosphorylase, the amino acid undergoing phosphorylation is

• a) Arginine

• b) Histidine

• c) Serine

• d) Tyrosine

c) Serine

Amino acids undergoing phosphorylation are mostly serine and threonine, more rarely tyrosine.

Dicarboxylic amino acids (Asp, Glu) can be found in the active site of an enzyme and may be phosphorylated during the catalytic cycle; however their phosphorylation is not used in pathways of signal transduction. Why?

Phosphoanhydrides with organic acids are not stable enough to be used in signal transduction pathways

Can you explain why allosteric regulation by ATP/AMP is important in muscle phosphorylase but not in the liver enzyme?

• Skeletal muscle is subject to changes in ATP/AMP levels due to its active (contraction)/inactive state

• Muscle phosphorylase yields Glucose-1-P and then glucose-6-P that can enter glycolysis if required for energy production

• The liver cells are not subjected to sudden changes in ATP concentration, and the role of liver phosphorylase is to enhance glycaemia under hormonal control (glucagon)

Explain why glycogen branching is advantageous for the cell.

• Results in many free 4-OH ends

• Since glycogen phosphorylase attacks the first glycosidic bond close to the 4-OH end of glycogen, many phosphorylase enzymes may attack glycogen at the same time, thus enhancing the rate of formation of glucose units that enter glycolysis or provide free glucose to blood.

Imagine that a new enzyme is discovered that catalyses the following reaction:

glyceraldehyde-3-P + NAD⁺ → 3-P-glycerate + NADH + H⁺

This reaction would shorten glycolysis but would give disadvantage to the cell. Explain why

Direct formation of 3-P-glycerate prevents formation of the high-energy bond needed for ATP formation

Pyruvate oxidation yields acetyl CoA, a high-energy compound. Explain where the high free energy of the thioester bond comes from.

It is the energy of oxidation of acetaldehyde (linked to TPP) by lipoic acid that is conserved as a high energy bond between the oxidized product (acetate) and the reduced product (dihydrolipoic acid) in the form of acetyl-lipoate. The high energy bond is then transferred by exchange with CoASH to form acetyl CoA.

Pyruvate dehydrogenase and α-ketoglutarate dehydrogenase are enzyme complexes formed by 3 enzymes called E1, E2 and E3. While E1 and E2 are respectively very similar but not identical in both complexes, E3 is identical. Why?

E3 catalyses the reduction of NAD+ by dihydrolipoate via endogenous FAD: this reaction is the same for the oxidation of pyruvate and of α-ketoglutarate. On the other hand, the reactions catalysed by E1 and E2 have different substrates.

Both pyruvate dehydrogenase and α-ketoglutarate dehydrogenase reactions yield high-energy thioesters, acetyl CoA and succinyl CoA, respectively. Energy of succinyl CoA is usually employed for substrate-level phosphorylation (GTP), but energy from acetyl CoA is not. Can you provide an explanation?

The high-energy bond of acetyl CoA is used to directly energize many different metabolic reactions and it would be wasteful to use it to make ATP.

Concerning muscle glycogen

• a) It is formed starting from blood glucose during exercise

• b) When broken down it contributes significantly to blood glucose levels

• c) Its breakdown occurs by reacting with inorganic phosphate

• d) Glucagon stimulates its breakdown

• e) The 1-6 glycosidic bond in its branches is broken by an isozyme of phosphorylase

c) Its breakdown occurs by reacting with inorganic phosphate

a) False. It is formed at rest and broken down during exercise

b) False. Muscle does not contain glucose-6-phosphatase

c) True. By glycogen phosphorylase

d) Wrong. Muscle does not have glucagon receptors

e) Wrong. It is hydrolysed by a glucosidase

Which of the following enzymes contains thiamine pyrophosphate?

• a) Pyruvate carboxylase

• b) Triose phosphate isomerase

• c) Transketolase

• d) Isocitrate dehydrogenase

c) Transketolase

What is a difference between succinate dehydrogenase and the other enzymes of the Krebs cycle?

• a) It is the only enzyme tightly bound to the inner membrane

• b) It is the only enzyme not present in the cytoplasm

• c) It is the only enzyme that catalyses an irreversible reaction

• d) It is the only enzyme that catalyses a substrate-level phosphorylation

a) It is the only enzyme tightly bound to the inner membrane

a) True. Succinate dehydrogenase corresponds to Complex II. The other enzymes are in the matrix

b) False. Also citrate synthase and succinyl CoA synthetase are only mitochondrial

c) False. Citrate synthase reaction is irreversible. Succinate dehydrogenase reaction can be reversed under special conditions.

d) False. It does not catalyse substrate-level phosphorylation

Only one answer is incorrect. Concerning blood glucose regulation:

• a) Under conditions of high blood sugar, the β cells secrete insulin

• b) Stimulation of insulin receptor stimulates the expression of enzymes involved in gluconeogenesis

• c) Many Type-2 diabetics have lower levels of plasma membrane localized GLUT-4 than non-diabetics

• d) Under conditions of high blood sugar, glycogen synthase is activated

• e) Glucagon increases the expression of glucose-6-phosphatase

b) Stimulation of insulin receptor stimulates the expression of enzymes involved in gluconeogenesis

a) True. The stimulus for insulin release from β cells is high glucose.

b) False. Insulin inhibits gluconeogenesis

c) True. GLUT4 is moved from internal vesicles to the plasma membrane by the action of insulin

d) True. By a cascade involving OI3 kinase and ending with dephosphorylation of glycogen synthase

e) True

Concerning gluconeogenesis

• a) It is regulated by changes in gene expression

• b) In liver cells the Krebs cycle runs at higher rate when gluconeogenesis is occurring

• c) Gluconeogenesis occurs after a meal rich in glucose

• d) Fasting depresses gluconeogenesis

• e) All 20 amino acids may serve as carbon skeletons for glucose synthesis

a) It is regulated by changes in gene expression

a) True, induced by glucagon and cortisol

b) False. Since oxaloacetate is reduced to malate and used as a precursor of gluconeogenesis, the Krebs cycle would run at lower rate.

c) False. It is inhibited by the action of insulin

d) False. Fasting induces hypoglycaemia and this stimulates glucagon secretion

e) False. Ketogenic amino acids are not precursors

How many ATP can be generated in the muscle during glycolysis by one glycogen breakdown product and why?

• a) 3 ATP, the first energy-requiring step of glycolysis is bypassed

• b) 2 ATP, glucose is formed during glycogen breakdown

• c) 4 ATP, glycogen breakdown generates extra energy

• d) 4 ATP, glycolysis begins at the energy pay-off phase

• e) 1 ATP, glycolysis requires more energy for proper activation

a) 3 ATP, the first energy-requiring step of glycolysis is bypassed

Glycogenolysis produces glucose-1-P without ATP consumption; G1P is isomerized to G6P, thus bypassing the hexokinase reaction that would consume 1 ATP.

Concerning glycogen metabolism

• a) During glycogen synthesis, glucose-1-P is converted to glucose-6-P

• b) The muscle primarily uses glucose-6-P for glycolysis

• c) Muscle glycogen phosphorylase is activated by glucagon

• d) In the phosphorylase reaction, the phosphate donor for forming glucose-1-P is UTP

• e) Glucose-6-phosphatase is present in liver mitochondria

b) The muscle primarily uses glucose-6-P for glycolysis

a) False. It is the opposite

b) True. Glycogen → glucose-1-P → glucose-6-P → enters glycolysis for ATP production. Unlike the liver, muscle lacks glucose-6-phosphatase, so it can’t release free glucose into blood

c) False. Skeletal muscle has no glucagon receptors

d) False. The reaction requires inorganic phosphate

e) False. It is in the endoplasmic reticulum

High levels of fructose-2,6-bisphosphate regulate glycolysis and gluconeogenesis by which of the following

• a) Increasing PFK-1 activity, decreasing glycolysis

• b) Increasing FBPase-1 activity, increasing gluconeogenesis

• c) Increasing FBPase-1 activity, increasing glycolysis

• d) Decreasing FBPase-1 activity, increasing glycolysis

• e) Preventing the binding of insulin to insulin receptor

d) Decreasing FBPase-1 activity, increasing glycolysis

Fructose-2,6-bisphosphate inhibits FBPase-1, thus decreasing gluconeogenesis, and activates PFK1, thus increasing glycolysis. It has no effect at the receptor level e)