Unit 12 Question Bank
Format note: the TMU Biochemistry paper gives five suggested
answers (A–E), not four — these MCQs match that. Items tagged TMU 2019 or
TMU 2020/21 come from the real papers. Answers are verified against Harper's
Illustrated Biochemistry; the "marking schemes" in the source folder are other students'
answer sheets, not official, so they are never used as the authority.
0 / 25 answered
1Glycogen is best described as ( ).
Answer: C
It corresponds to starch in plants. It occurs mainly in liver (up to 6%) and muscle (rarely over 1%) — but because of its greater mass, muscle contains three to four times as much in total. Examiners set that pair of figures deliberately.Harper's ch.18, p.176 · TMU Lecture 12 Slide 3
2Which tissue contains the GREATER TOTAL AMOUNT of glycogen?
Answer: D
Two facts that appear to contradict each other and do not. Liver has the higher concentration (up to 6% vs 1%); muscle has the greater total, three to four times more. They point at the two different purposes: liver as a concentrated export depot, muscle as a large private fuel tank.Harper's ch.18, p.176
3Muscle glycogen cannot raise blood glucose because muscle lacks ( ).
Answer: E
Glycogenolysis in either tissue yields glucose 6-phosphate, and phosphorylated sugars cannot cross the plasma membrane. Only liver and kidney possess the phosphatase that hydrolyses glucose 6-phosphate, yielding glucose that is exported. This single enzymatic difference is why hepatic glycogen governs blood sugar and muscle glycogen governs sprinting.Harper's ch.18, p.178 · TMU Lecture 12 Slide 18
4After approximately how long a fast is liver glycogen almost totally depleted?
Answer: A
That number is worth carrying, because it is the reason gluconeogenesis must exist. Overnight, glycogen covers you; beyond about a day the liver must manufacture glucose from non-carbohydrate precursors or the brain fails.Harper's ch.18, p.176 · TMU Lecture 12 Slide 5
5The activated form of glucose used in glycogen synthesis is ( ).
Answer: B
Glucose 1-phosphate reacts with UTP to form UDP-glucose (UDPGlc) and pyrophosphate, catalysed by UDPGlc pyrophosphorylase. The phrase to use is “a special nucleotide of glucose” — or, as the slides put it, “active glucose”.Harper's ch.18, p.177 · TMU Lecture 12 Slide 7
6Pyrophosphatase is important in glycogenesis because it ( ).
Answer: C
It adds nothing to the glycogen — its whole function is to destroy one of the products of the previous step so that it cannot run backwards. This is exactly Unit 8's device for ATP → AMP + PPi: the cell pays an extra high-energy bond to buy directionality.Harper's ch.18, p.177 · TMU Lecture 12 Slide 9
7Glycogen synthase forms a glycosidic bond between ( ).
Answer: D
A 1→4 linkage, liberating UDP. Branch points (1→6) are made separately by branching enzyme. Crucially, a pre-existing “glycogen primer” must be present — glycogen synthase can only extend a chain, never start one.Harper's ch.18, p.177 · TMU Lecture 12 Slide 10
8Glycogenin is ( ).
Answer: E
Every glycogen granule has a protein at its core. Further glucose residues are attached in the 1→4 position to make a short chain that is then a substrate for glycogen synthase. A tissue difference worth quoting: in skeletal muscle glycogenin remains in the centre of the molecule, whereas in liver glycogen molecules outnumber glycogenin molecules.Harper's ch.18, p.177 · TMU Lecture 12 Slides 10–11
9Branching enzyme acts when a chain reaches at least ( ) glucose residues, transferring at least ( ) residues.
Answer: A
It transfers part of a 1→4 chain to a neighbouring chain to form a 1→6 linkage, establishing a branch point. Branching serves two purposes: solubility, and — more importantly — creating many non-reducing ends so that phosphorylase can attack from many points at once.Harper's ch.18, p.178 · TMU Lecture 12 Slide 12
10Which statement about glycogenolysis is correct?
Answer: B
This is the sentence to open any glycogenolysis answer with. Unit 7's principle: a pathway and its opposite must use different enzymes at the irreversible steps, or they could not be independently regulated. Synthesis uses UDPGlc and glycogen synthase; breakdown uses phosphorolysis by phosphorylase.TMU Lecture 12 Slide 15 · Harper's ch.18, p.177
11Glycogen phosphorylase catalyses ( ).
Answer: C
Note the word: phosphorolysis uses inorganic phosphate, not water. So the product is already phosphorylated — saving the ATP that hexokinase would otherwise spend. In an emergency, muscle gets its glucose into glycolysis for free. It catalyses the rate-limiting step.Harper's ch.18, p.177 · TMU Lecture 12 Slide 15
12Phosphorylase stops removing glucose residues when approximately how many remain on either side of a 1→6 branch?
Answer: D
At that point a transferase moves a trisaccharide unit from one branch to the other, exposing the 1→6 branch point, and debranching enzyme hydrolyses the 1→6 linkage. Further phosphorylase action can then proceed.Harper's ch.18, p.178 · TMU Lecture 12 Slides 15, 17
13Hydrolysis of the 1→6 linkages of glycogen requires ( ).
Answer: E
Two activities are needed at a branch: a transferase to move a trisaccharide and expose the branch point, then debranching enzyme to hydrolyse the 1→6 bond. Note that this step is a hydrolysis, so it yields free glucose rather than glucose 1-phosphate.Harper's ch.18, p.178
14Cyclic AMP is formed from ATP by ( ) and hydrolysed by ( ).
Answer: A
cAMP is formed by adenylyl cyclase at the inner surface of cell membranes and acts as an intracellular second messenger in response to epinephrine, norepinephrine and glucagon. It is hydrolysed by phosphodiesterase, terminating hormone action — and in liver, insulin increases phosphodiesterase activity.Harper's ch.18, p.180 · TMU Lecture 12 Slide 21
15Place the cAMP cascade in the correct order.
Answer: B
Four steps to switch on one enzyme is amplification: one hormone molecule makes many cAMP, each activating a kinase, each phosphorylating many molecules of the next enzyme. The scale is real — glycogenolysis increases several hundred-fold immediately after the onset of contraction.Harper's ch.18, p.181 · TMU Lecture 12 Slide 25
16Muscle phosphorylase b is ( ).
Answer: C
Phosphorylase a is phosphorylated and active in either the presence or absence of 5′-AMP, and is the normal physiologically active form. Phosphorylase b is dephosphorylated and needs AMP — which rises during exercise, providing fuel for the muscle by that mechanism alone.Harper's ch.18, p.181 · TMU Lecture 12 Slide 24
17Muscle phosphorylase contains which vitamin-derived cofactor?
Answer: D
Muscle phosphorylase is a dimer, each monomer containing 1 mol of pyridoxal phosphate. This is a distinctive fact — pyridoxal phosphate is otherwise associated with transaminases, so its appearance here is often tested.Harper's ch.18, p.181 · TMU Lecture 12 Slide 24
18The δ subunit of muscle phosphorylase kinase is identical to ( ).
Answer: E
Phosphorylase kinase has the structure (αβγδ)₄. The α and β subunits carry the serines phosphorylated by cAMP-dependent protein kinase; the δ subunit binds four Ca²⁺ and IS calmodulin. So the nerve impulse that tells the muscle to contract simultaneously tells it to burn glycogen — supply switched on by the signal for demand.Harper's ch.18, pp.180–181 · TMU Lecture 12 Slide 27
19Binding of Ca²⁺ to phosphorylase kinase ( ).
Answer: A
This is the important subtlety: the enzyme can be switched on by calcium alone, without any hormone at all. The phosphorylated a form is of course also active. Compare Unit 11 §9, where Ca²⁺ activates the citric acid cycle for the same physiological reason.Harper's ch.18, p.181 · TMU Lecture 12 Slide 28
20Phosphorylation of the enzymes of glycogen metabolism has which effect?
Answer: B
One signal, two opposite effects — so the cell can never break down and synthesise glycogen at once. The rule to memorise: for glycogen, phosphorylation means BREAKDOWN. Anchor it to “adrenaline phosphorylates, and adrenaline wants glucose released” — but do not generalise it to other pathways.Harper's ch.18, pp.181–183
21Insulin lowers hepatic cAMP by ( ).
Answer: C
The result is that enzymes become dephosphorylated — so glycogen synthase is activated and phosphorylase inactivated, and glucose is stored. This is the mechanism behind the 2020/21 Section II question on reciprocal regulation.Harper's ch.18, p.180 · TMU Lecture 12 Slide 21
22Glucagon acts mainly on the LIVER rather than on muscle because ( ).
Answer: D
Glucagon's job is to raise blood glucose, so it acts where the exporting enzyme exists. Epinephrine acts on muscle as well — but muscle has no phosphatase, so the glucose stays put and fuels the muscle itself. Same second messenger, same cascade, two outcomes — decided by one enzyme.Harper's ch.18, p.178 · TMU Lecture 12 Slide 21
23Von Gierke's disease (type I glycogen storage disease) is caused by deficiency of ( ).
Answer: E
Liver glycogen accumulates but cannot be exported as glucose, so the patient has severe fasting hypoglycaemia despite abundant stores, with hepatomegaly and lactic acidosis. It is §2's table with the liver's key enzyme removed.Harper's ch.18, p.179
24McArdle's syndrome results from deficiency of ( ), and presents with ( ).
Answer: A
Blood glucose is normal, but the muscle cannot access its own fuel. The absent rise in lactate on exercise is the diagnostic clue — the muscle cannot even reach glycolysis from its glycogen. It is §2's table with the muscle's key enzyme removed.Harper's ch.18, p.179
25Glycogen storage diseases are best defined as ( ).
Answer: B
They lead to muscular weakness or even death. The two named examples are von Gierke's (type I, glucose-6-phosphatase) and McArdle's (type V, muscle phosphorylase) — one hepatic, one muscular, mapping exactly onto the two purposes of glycogen.Harper's ch.18, p.176 · TMU Lecture 12 Slide 5
1 Glycogen — 2′+
The major storage carbohydrate in animals, corresponding to starch in plants; a branched polymer of α-D-glucose.
It occurs mainly in liver (up to 6%) and muscle (rarely exceeding 1%) — but because of its greater mass, muscle contains about three to four times as much glycogen as liver. Muscle glycogen is a readily available source of glucose for glycolysis within the muscle itself; liver glycogen stores and exports glucose to maintain blood glucose between meals, and is almost totally depleted after 12–18 hours of fasting.Harper's ch.18, p.176
It occurs mainly in liver (up to 6%) and muscle (rarely exceeding 1%) — but because of its greater mass, muscle contains about three to four times as much glycogen as liver. Muscle glycogen is a readily available source of glucose for glycolysis within the muscle itself; liver glycogen stores and exports glucose to maintain blood glucose between meals, and is almost totally depleted after 12–18 hours of fasting.Harper's ch.18, p.176
2 Glycogenesis — 3′+
The synthesis of glycogen, occurring mainly in muscle and liver.
Glucose is phosphorylated to glucose 6-phosphate (hexokinase in muscle, glucokinase in liver), isomerised to glucose 1-phosphate by phosphoglucomutase, and converted with UTP to the active nucleotide UDP-glucose by UDPGlc pyrophosphorylase — the reaction being pulled forward by pyrophosphatase hydrolysing the PPi.
Glycogen synthase then forms a glycosidic bond between C1 of the activated glucose and C4 of a terminal residue of a pre-existing glycogen primer, itself formed on glycogenin. When a chain reaches at least 11 residues, branching enzyme transfers at least six to a neighbouring chain to form a 1→6 branch point.Harper's ch.18, pp.176–178
Glucose is phosphorylated to glucose 6-phosphate (hexokinase in muscle, glucokinase in liver), isomerised to glucose 1-phosphate by phosphoglucomutase, and converted with UTP to the active nucleotide UDP-glucose by UDPGlc pyrophosphorylase — the reaction being pulled forward by pyrophosphatase hydrolysing the PPi.
Glycogen synthase then forms a glycosidic bond between C1 of the activated glucose and C4 of a terminal residue of a pre-existing glycogen primer, itself formed on glycogenin. When a chain reaches at least 11 residues, branching enzyme transfers at least six to a neighbouring chain to form a 1→6 branch point.Harper's ch.18, pp.176–178
3 Glycogenolysis — 3′+
The breakdown of glycogen — and not the reverse of glycogenesis, but a separate pathway.
Glycogen phosphorylase catalyses the rate-limiting step, promoting the phosphorolytic cleavage by inorganic phosphate of the 1→4 linkages to yield glucose 1-phosphate. Terminal residues are removed until about four remain on either side of a 1→6 branch; a transferase then moves a trisaccharide to expose the branch point, and debranching enzyme hydrolyses the 1→6 linkage.
Glucose 1-phosphate is converted to glucose 6-phosphate by phosphoglucomutase. In liver and kidney, but not muscle, glucose-6-phosphatase hydrolyses this to free glucose for export.Harper's ch.18, pp.177–178
Glycogen phosphorylase catalyses the rate-limiting step, promoting the phosphorolytic cleavage by inorganic phosphate of the 1→4 linkages to yield glucose 1-phosphate. Terminal residues are removed until about four remain on either side of a 1→6 branch; a transferase then moves a trisaccharide to expose the branch point, and debranching enzyme hydrolyses the 1→6 linkage.
Glucose 1-phosphate is converted to glucose 6-phosphate by phosphoglucomutase. In liver and kidney, but not muscle, glucose-6-phosphatase hydrolyses this to free glucose for export.Harper's ch.18, pp.177–178
4 Glycogenin — 2′+
A 37-kDa protein which is glycosylated on a specific tyrosine residue by UDPGlc, and on which the glycogen primer is formed.
It is needed because glycogen synthase can only extend an existing chain, never start one. Further glucose residues are attached in the 1→4 position to make a short chain that then becomes a substrate for glycogen synthase. In skeletal muscle glycogenin remains attached at the centre of the glycogen molecule; in liver, glycogen molecules outnumber glycogenin molecules.Harper's ch.18, p.177
It is needed because glycogen synthase can only extend an existing chain, never start one. Further glucose residues are attached in the 1→4 position to make a short chain that then becomes a substrate for glycogen synthase. In skeletal muscle glycogenin remains attached at the centre of the glycogen molecule; in liver, glycogen molecules outnumber glycogenin molecules.Harper's ch.18, p.177
5 Glycogen storage disease — 2′+
One of a group of inherited disorders characterised by deficient mobilisation of glycogen or deposition of abnormal forms of glycogen, leading to muscular weakness or even death.
Von Gierke's disease (type I) — deficiency of glucose-6-phosphatase: hepatic glycogen accumulates but cannot be exported, causing severe fasting hypoglycaemia.
McArdle's syndrome (type V) — deficiency of muscle glycogen phosphorylase: exercise intolerance and cramps, with no rise in blood lactate on exercise.Harper's ch.18, pp.176, 179
Von Gierke's disease (type I) — deficiency of glucose-6-phosphatase: hepatic glycogen accumulates but cannot be exported, causing severe fasting hypoglycaemia.
McArdle's syndrome (type V) — deficiency of muscle glycogen phosphorylase: exercise intolerance and cramps, with no rise in blood lactate on exercise.Harper's ch.18, pp.176, 179
1
Explain how insulin and glucagon regulate glycogenesis and glycogenolysis reciprocally.
5′ — ⭐ ASKED IN THE 2020/21 PAPER
The principle
The two principal enzymes of glycogen metabolism — glycogen phosphorylase and glycogen synthase — are regulated by allosteric mechanisms and by covalent modification through reversible phosphorylation and dephosphorylation in response to hormone action.
Regulation is reciprocal because the same phosphorylation event that activates phosphorylase simultaneously inactivates glycogen synthase. One signal, two opposite effects — so the cell can never break down and synthesise glycogen at the same time, which would be a futile cycle.
The second messenger
Cyclic AMP is formed from ATP by adenylyl cyclase at the inner surface of the cell membrane, and acts as an intracellular second messenger in response to hormones such as epinephrine, norepinephrine and glucagon. It is hydrolysed by phosphodiesterase, terminating hormone action.
Glucagon (and epinephrine) — the fasting signal
Glucagon responds to a fall in blood glucose. It increases cAMP, which activates cAMP-dependent protein kinase. This catalyses the phosphorylation of inactive phosphorylase kinase b to active phosphorylase kinase a, which in turn, by a further phosphorylation, activates phosphorylase b to phosphorylase a.
The same protein kinase simultaneously phosphorylates and inactivates glycogen synthase.
Net effect: glycogenolysis proceeds and glycogenesis stops — glucose is released.
Insulin — the fed signal
Insulin responds to a rise in blood glucose. In liver, insulin increases the activity of phosphodiesterase, which hydrolyses cAMP. With cAMP low, cAMP-dependent protein kinase is inactive, and the enzymes are progressively dephosphorylated by protein phosphatase-1.
Dephosphorylation inactivates phosphorylase (a → b) and activates glycogen synthase.
Net effect: glycogenesis proceeds and glycogenolysis stops — glucose is stored.
| Glucagon / epinephrine | Insulin | |
|---|---|---|
| cAMP | ↑ | ↓ (via phosphodiesterase) |
| Enzymes are | Phosphorylated | Dephosphorylated |
| Glycogen phosphorylase | Activated | Inactivated |
| Glycogen synthase | Inactivated | Activated |
| Net | Glycogenolysis | Glycogenesis |
The tissue difference
Glucagon acts mainly on liver, because its purpose is to raise blood glucose and only liver and kidney possess glucose-6-phosphatase to export free glucose. Epinephrine also acts on muscle — but muscle lacks that phosphatase, so the glucose released fuels the muscle itself. In muscle there is a further, hormone-independent route: Ca²⁺ activates phosphorylase kinase directly through its δ subunit, which is calmodulin, synchronising glycogenolysis with contraction.
Marking guide: reciprocal principle stated — one phosphorylation with opposite effects 1 · cAMP formed by adenylyl cyclase and hydrolysed by phosphodiesterase 1 · the glucagon cascade traced to phosphorylase a 1 · insulin acting via phosphodiesterase and dephosphorylation 1 · both enzymes' responses given in both states 0.5 · the liver/muscle tissue difference or the Ca²⁺ route 0.5.
2
Outline briefly the pathway of glycogenolysis.
5′ — 'outline briefly'
An important opening statement
Glycogenolysis is not the reverse of glycogenesis but is a separate pathway, using different enzymes and different chemistry — which is what allows the two to be regulated independently.
The steps
- Glycogen phosphorylase catalyses the rate-limiting step, promoting the phosphorolytic cleavage by inorganic phosphate (phosphorolysis, cf. hydrolysis) of the 1→4 linkages of glycogen to yield glucose 1-phosphate. Terminal glucosyl residues are removed sequentially from the outermost chains until approximately four glucose residues remain on either side of a 1→6 branch.
- A transferase then transfers a trisaccharide unit from one branch to the other, exposing the 1→6 branch point.
- Hydrolysis of the 1→6 linkage requires the debranching enzyme. Further phosphorylase action can then proceed, and the combined action of these enzymes leads to complete breakdown of the glycogen.
- Phosphoglucomutase converts glucose 1-phosphate to glucose 6-phosphate; this reaction is reversible, so the same enzyme serves both pathways.
- In liver and kidney, but not in muscle, glucose-6-phosphatase hydrolyses glucose 6-phosphate, yielding glucose that is exported, leading to an increase in blood glucose concentration.
Why phosphorolysis rather than hydrolysis
Because the product, glucose 1-phosphate, is already phosphorylated. Had glycogen been hydrolysed to free glucose, the cell would have to spend ATP at hexokinase to phosphorylate it again — so phosphorolysis gets glucose into glycolysis at no ATP cost, which is exactly what is wanted in muscle during exercise.
Control
Phosphorylase is activated by phosphorylation, through the cascade epinephrine → cAMP → cAMP-dependent protein kinase → phosphorylase kinase b to a → phosphorylase b to a. In muscle it is additionally activated by Ca²⁺, acting on the δ (calmodulin) subunit of phosphorylase kinase — the same signal that initiates contraction — so that glycogenolysis increases several hundred-fold immediately after the onset of contraction.
Marking guide: statement that it is a separate pathway 0.5 · phosphorylase and phosphorolysis to glucose 1-phosphate 1.5 · stopping four residues from the branch 0.5 · transferase and debranching enzyme 1 · phosphoglucomutase and the liver-only glucose-6-phosphatase 1 · the control cascade or the Ca²⁺ mechanism 0.5.