Gluconeogenesis + Glycogen Metabolism

Question 1

Skeletal muscle, unlike the liver, cannot contribute to the maintenance of blood glucose levels because muscle lacks the enzyme _____

(a) glucose 6-phosphatase
(b) phosphoglucoisomerase
(c) hexose diphosphatase
(d) glucokinase
(e) hexokinase

Answer 1

A

Question 2

Gluconeogenesis is the _____

(a) result of amylase activity
(b) formation of glycogen
(c) formation of starches
(d) formation of glucose from simple two and three-carbon precursors
(e) formation of glucose from other carbohydrates

Answer 2

D

Question 3

The _____ is the site of most gluconeogenesis in mammals.

(a) liver
(b) pancreas
(c) mitochondria of all cells
(d) cytosol of all cells
(e) small intestine

Answer 3

A

Question 4

Gluconeogenesis shares some, but not all, enzymes with the glycolytic pathway. It would appear to be more efficient if both pathways used all of the same enzymes since the pathways are essentially the reverses of each other. Why don’t both pathways use all of the same enzymes?

(a) The reactions where enzymes differ occur in different parts of the cell for glycolysis versus gluconeogenesis.
(b) Enzymes can catalyse a reaction only in one direction, so naturally the two pathways have some enzymes that differ.
(c) In tissues where gluconeogenesis occurs, the glycolytic enzymes are present at extremely low concentrations.
(d) Three of the reaction steps in gluconeogenesis would have prohibitively large, positive free energies if they used glycolytic enzymes for their catalysis.
(e) None of the above explanations are correct.

Answer 4

D

Question 5

Which of the following statements is correct about the enzyme
phosphofructokinase-2?

(a) It forms a multienzyme complex with fructose 2,6-bisphosphatase in combination with coenzymes.
(b) It is a bifunctional enzyme with fructose 2,6-bisphosphatase activity.
(c) It is an isoenzyme of phosphofructokinase-1.
(d) It has its activity modified by fructose 1,6-bisphosphate.
(e) All of the above statements are correct.

Answer 5

B

Question 6

Animals lack the ability to produce glucose from _____
(a) other sugars
(b) fatty acids
(c) pyruvate
(d) amino acids
(e) starch

Answer 6

B

Question 7

The activity of phosphoenolpyruvate carboxykinase (PEPCK) is most affected by:

(a) glucagon concentration.
(b) insulin concentration.
(c) the level of PEPCK gene transcription.
(d) the elevation of cAMP concentration on fasting.
(e) none of the above.

Answer 7

C

Question 8

In the Cori cycle, gluconeogenesis occurs in _____ and glycolysis in _____

(a) liver; muscle
(b) liver; liver
(c) brain; muscle
(d) muscle; liver
(e) liver; erythrocytes

Answer 8

A

Question 9

Fructose 2,6-bisphosphate _____ glycolysis while it _____ gluconeogenesis.

(a) activates; stimulates
(b) stimulates; inhibits
(c) inhibits; stimulates
(d) inhibits; deactivate
(e) deactivate; activate

Answer 9

B

Question 10

Why does glycolysis produce more energy (more ATP) from glucose units released by glycogen degradation than from free glucose?

(a) Glucose 1-phosphate feeds into the glycolysis pathway bypassing two reactions.
(b) The debranching enzyme releases free glucose.
(c) The glucose is already phosphorylated after glycogen phosphorylase action.
(d) The glucose from glycogen degradation does not need to be transported into the mitochondria.
(e) All of the above

Answer 10

C

Question 11

Glucose 1-phosphate formed by glycogen degradation is converted to glucose 6- phosphate by phosphoglucomutase. Why is this beneficial?

(a) Glucose 6-phosphate is more stable.
(b) Glucose 6-phosphate is converted to free glucose.
(c) Glucose 6-phosphate is an intermediate in several pathways, including glycolysis.
(d) Glucose 6-phosphate can be transported to the liver.
(e) All of the above.

Answer 11

C

Question 12

How is glycogen phosphorylase b converted into glycogen phosphorylase a?

(a) Addition of a phosphate to a serine residue.
(b) Dimerization, which forms the active site pocket.
(c) Cleavage of 10 amino acids from the N-terminal end of the protein.
(d) All of the above mechanisms are correct.
(e) None of the above mechanisms are correct

Answer 12

A

Question 13

Glycogen synthesis in vertebrates requires to activate
glucose 1-phosphate.

(a) ATP
(b) ADP
(c) UTP
(d) UDP
(e) All of the above

Answer 13

C

Question 14

What is the function of liver glycogen degradation?

(a) For glucose export to other tissues when glucose levels are low.
(b) To maintain glucose levels after a large meal.
(c) To provide for the large energy needs of the liver.
(d) All of the above.
(e) None of the above

Answer 14

A

Question 15

Which of the following statements about glycogen is true?

i. Glycogen is a polymer of glucose in α(1−>6) linkages with α(1−>4)
linked branches every 8–14 residues.
ii. UDP–glucose is produced from glycogen by the action of the enzyme phosphorylase.
iii. In glycogen breakdown, glucose residues are sequentially removed from the nonreducing ends.
iv. The breakdown of glycogen in skeletal muscle ultimately supplies glucose-6-phosphate, which can enter glycolysis to generate ATP.

(a) i, ii, iii, and iv
(b) i and ii
(c) ii, iii, and iv
(d) iii and iv
(e) iii only

Answer 15

D

Question 16

Phosphorylation can be used as a biochemical switch to either activate or inactivate enzymes. This is a key element in the regulation of glycogen metabolism. Phosphorylation of glycogen synthase _____ it; phosphorylation of glycogen phosphorylase _____ it.

(a) activates; stimulates
(b) activates; inactivates
(c) inhibits; inactivates
(d) inactivates; activates
(e) downregulates, upregulates

Answer 16

D

Question 17

Why is glycogen branching important?

(a) Branching significantly alters the melting point.
(b) Branching increases the solubility of glycogen.
(c) Branching increases glycogen synthesis and degradation by increasing the potential sites of action.
(d) Branching improves glycogen transport
(e) Answers (b) and (c) are correct.
(f) Answers (c) and (d) are correct

Answer 17

E

Question 18

Which metabolic steps differ from glycolysis in gluconeogenesis?

Answer 18

There are three irreversible steps in glycolysis, which require four different steps in gluconeogenesis:
* pyruvate conversion to phosphoenolpyruvate via an oxaloacetate
intermediate,
* fructose 1,6-bisphosphate hydrolysis,
* the hydrolysis of glucose 6-phosphate.

Question 19

How are gluconeogenesis and glycolysis regulated reciprocally?

Answer 19

The enzymes involved in two substrate cycles are control points.
In glycolysis, F-2,6-BP, AMP, and F-1,6-BP activation the pathway; whereas ATP, alanine, citrate, and protons inhibit glycolysis.
Gluconeogenesis is activated by citrate and acetyl CoA and inhibited by F-2,6- BP, AMP, and ADP

Question 20

Under what circumstances does the bifunctional protein phosphofructokinase-2/fructose 2,6-bisphosphatase (PFK-2/FBPase-2) become phosphorylated, and what are the consequences of its phosphorylation to the glycolytic and gluconeogenic pathways?

Answer 20

Glucagon, signalling low blood sugar, stimulates cAMP synthesis, which activates protein kinase A (PKA) to phosphorylate PFK-2/FBPase-2 (among other proteins). This phosphorylation enhances FBPase-2 activity and inhibits PFK-2 activity of the enzyme, resulting in lower levels of fructose 2,6- bisphosphate (F26BP). In the
absence of F26BP as an allosteric effector, the activity of PFK-1 is reduced (inhibiting glycolysis) and the activity of FBPase-1 is enhanced (stimulating gluconeogenesis), thus enabling the liver to replenish blood glucose

Question 21

In the glycolytic path from glucose to phosphoenolpyruvate, two steps are practically irreversible. What are these steps, and how is each bypassed in gluconeogenesis? What advantages does an organism gain from having separate pathways for anabolic and catabolic metabolism? What are the disadvantages?

Answer 21

The two irreversible steps in glycolysis are the conversion of glucose to glucose 6-phosphate (catalysed by hexokinase) and the conversion of fructose 6-phosphate to fructose 1,6-bisphosphate (catalysed by
phosphofructokinase-1). The first reaction is bypassed during gluconeogenesis by the reaction catalysed by glucose 6-phosphatase, an enzyme unique to the liver. The second is bypassed by fructose 1,6-bisphosphatase-1 (FBPase-1). By having separate pathways that employ different enzymes, an organism can control anabolic and catabolic processes separately, thus avoiding futile cycles. A potential disadvantage is the need to produce separate sets of enzymes for catabolism and anabolism

Question 22

The glycogen molecule has two types of linkages between the glucose molecules of which it is comprised. Of these, the _____ linkage is broken by the glycogen phosphorylase enzyme and the _____ linkage is not. A separate enzyme called debranching enzyme breaks _____ linkages.

Need to choose between: α -1,4 and α -1,6

Answer 22

1) α -1,4
2) α -1,6
3) α -1,6

Question 23

Glycogen synthesis and glycogen breakdown are catalysed by separate enzymes. Which are the key regulatory steps in these pathways? Explain briefly how high levels of insulin affect the activity of these controlling enzymes in the liver

Answer 23

The key regulatory steps in glycogen metabolism are the reactions that add or remove the glucose monomers to the linear glycogen chain. That means that glycogenesis is controlled through the activity of glycogen synthase, while the manipulation of glycogen phosphorylase rates influences glycogenolysis. Protein phosphatase-1 (PP1) is activated if insulin levels are increased in response to
high blood glucose concentrations. Active PP1 dephosphorylates and activates glycogen synthase and, hence, glycogenesis. Glycogen phosphorylase is also dephosphorylated by protein phosphatase-1 (PP1). However, this changes glycogen phosphorylase to its less active b form, which slows down glycogen breakdown.

Question 24

Explain the role of glycogenin

Answer 24

Glycogenin is a protein that acts as the “primer” for the initiation of new glycogen molecules. It is an enzyme (EC 2.4.1.186 – glycogenin glucosyltransferase) that catalyses the transfer of a glucose residue from UDP- glucose to a tyrosine hydroxyl group in glycogenin, then forms a complex with glycogen synthase. Indeed, glycogen synthase is only catalytically efficient when it is bound to glycogenin. As more glucose residues are added, this first glucose residue, still attached to
glycogenin, becomes the reducing end of the growing glycogen chain

Question 25

Why must the control of glycogen metabolism be different in muscle and liver?

Answer 25

It is because the muscle maintains glucose for its own use, whereas the liver maintains glucose homeostasis for the whole organism

Question 26

What are the possible fates of the glucose 1-phosphate derived from glycogen in the liver?

Answer 26

Glucose 1-phosphate is:
1) converted into glucose 6-phosphate and used for glycolysis;
2) converted into glucose 6-phosphate and processed in the pentose
phosphate pathway to produce NADPH and pentoses;
3) converted into glucose 6-phosphate which is hydrolysed to glucose for release into the blood