Unit 13 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
1Gluconeogenesis is best defined as ( ).
Answer: D
Note the two words most students drop. “…or glycogen” — the product need not stop at glucose. And “all pathways”, plural — this is a family of routes converging on one destination. The major substrates are the glucogenic amino acids, lactate, glycerol and propionate; the major tissues are liver and kidney.TMU Lecture 12b Slide 3 · Harper's ch.19, p.184
2Which of the following can NOT be converted to glucose in significant amounts?
Answer: E
Because pyruvate dehydrogenase is irreversible (Unit 10). Once carbon has become acetyl-CoA it can never return to pyruvate — which is why you cannot live on fat alone, and why prolonged starvation must eventually consume muscle protein to supply glucogenic amino acids for the brain.Harper's ch.19, p.184 · Harper's ch.17, p.173
3Which tissues are the major sites of gluconeogenesis?
Answer: A
They are the tissues that possess the full complement of bypass enzymes — critically glucose-6-phosphatase, which muscle lacks. This is the same enzyme that determines whether glycogen can be exported (Unit 12).TMU Lecture 12b Slide 3
4How many reactions of glycolysis are irreversible and must therefore be bypassed in gluconeogenesis?
Answer: B
Three non-equilibrium reactions prevent simple reversal of glycolysis: pyruvate ⇌ phosphoenolpyruvate, fructose 1,6-bisphosphate ⇌ fructose 6-phosphate, and glucose 6-phosphate ⇌ glucose. The other seven steps are freely reversible and are simply run backwards. Note that three irreversible steps need four bypass enzymes, because the first takes two.TMU Lecture 12b Slide 6 · Harper's ch.19, p.185
5The conversion of pyruvate to phosphoenolpyruvate requires which two enzymes?
Answer: C
The drop from PEP to pyruvate is the largest free-energy fall in glycolysis — PEP is at −61.9 kJ/mol, the top of Unit 8's table — so climbing back costs more than one reaction can pay for. Pyruvate carboxylase (mitochondrial, ATP, biotin) makes oxaloacetate; PEP carboxykinase then decarboxylates it using GTP.Harper's ch.19, pp.185–186
6Pyruvate carboxylase requires which vitamin-derived cofactor?
Answer: D
Biotin — the carboxylation cofactor, as it is for acetyl-CoA carboxylase in fatty acid synthesis (Unit 16). The reaction occurs in the mitochondrion and uses ATP.Harper's ch.19, p.185
7In the pyruvate → PEP bypass, CO₂ is added and then immediately removed. The purpose is that ( ).
Answer: E
The cell adds a carboxyl group solely so that losing it again can pay for the phosphorylation. Not waste — a thermodynamic device, and the same logic as coupling in Unit 8. Note too that pyruvate carboxylase is simultaneously the main anaplerotic reaction of the citric acid cycle (Unit 11): one reaction serving two pathways.Harper's ch.19, pp.185–186 · Harper's ch.16, p.164
8Which enzyme catalyses the final step of gluconeogenesis, and where is it found?
Answer: A
The same enzyme that lets the liver export glucose from glycogenolysis (Unit 12). Its restriction to liver and kidney is exactly why those are the gluconeogenic tissues — and its deficiency is von Gierke's disease.Harper's ch.19, p.186 · Harper's ch.18, p.178
9Propionate enters gluconeogenesis by conversion to ( ).
Answer: B
Propionate is the principal glucogenic fatty acid produced in the digestion of carbohydrates by ruminants, and is a major substrate for gluconeogenesis in those species. It is the notable exception to the rule that fatty acids cannot make glucose — because it enters as a cycle intermediate rather than as acetyl-CoA.Harper's ch.19, p.187 · TMU Lecture 12b Slide 5
10The Cori cycle describes ( ).
Answer: C
It is energetically expensive for the liver — which is why it appears as the oxygen debt after exercise (Unit 10) and as the hypermetabolism of cancer cachexia. Gluconeogenesis also thereby clears the lactate produced by muscle and erythrocytes and the glycerol produced by adipose tissue.Harper's ch.19, p.191
11Why must glycolysis and gluconeogenesis be reciprocally regulated?
Answer: D
“Since glycolysis and gluconeogenesis share the same pathway but operate in opposite directions, their activities are regulated reciprocally.” Without that reciprocity the cell would achieve nothing but the hydrolysis of ATP.TMU Lecture 12b Slide 24
12Which three mechanisms regulate the enzymes of carbohydrate metabolism?
Answer: E
These are Unit 7's three mechanisms in Unit 7's order of speed: enzyme synthesis takes hours and serves long-term adaptation; covalent modification and allosteric effects act within seconds and serve rapid, transient change.TMU Lecture 12b Slide 10
13Glucagon inhibits glycolysis in the liver by causing the phosphorylation and inactivation of ( ).
Answer: A
Glucagon — and to a lesser extent epinephrine — inhibits glycolysis and stimulates gluconeogenesis in the liver by increasing the concentration of cAMP, which activates cAMP-dependent protein kinase. Note this is the same mechanism that activates glycogenolysis in Unit 12: one signal, two pathways, both pointing towards raising blood glucose.Harper's ch.19, p.188 · TMU Lecture 12b Slide 14
14Fructose 2,6-bisphosphate is ( ).
Answer: B
One molecule, two enzymes, opposite effects — reciprocal regulation compressed into a single compound. It activates the key enzyme of glycolysis and inhibits the corresponding enzyme of gluconeogenesis.Harper's ch.19, pp.188–189 · TMU Lecture 12b Slide 16
15Fructose 2,6-bisphosphate is formed and degraded by ( ).
Answer: C
A single polypeptide with a kinase domain and a phosphatase domain. Which activity dominates is decided by phosphorylation of that protein by cAMP-dependent protein kinase — so glucagon flips the enzyme from kinase to phosphatase mode. One hormone → one phosphorylation → one metabolite → both pathways switch at once.Harper's ch.19, p.189 · TMU Lecture 12b Slide 17
16How does fructose 2,6-bisphosphate differ from fructose 1,6-bisphosphate?
Answer: D
Fructose 1,6-bisphosphate is a metabolic intermediate, the product of PFK-1 in the middle of glycolysis. Fructose 2,6-bisphosphate is not on the pathway at all — it exists purely to control PFK-1 and FBPase-1. Same atoms, different phosphate position, completely different job. Examiners set this deliberately.Harper's ch.19, pp.188–189
17In the FASTING state, the level of hepatic fructose 2,6-bisphosphate is ( ), and the net effect is ( ).
Answer: E
Glucagon raises cAMP → the bifunctional enzyme is phosphorylated and switches to phosphatase mode → fructose 2,6-bisphosphate falls → PFK-1 loses its activator and fructose 1,6-bisphosphatase loses its inhibitor → gluconeogenesis proceeds and glycolysis stops.Harper's ch.19, pp.189–190
18Enzymes of glucose utilisation become more active when glucose is abundant, while gluconeogenic enzymes have low activity. This is an example of ( ).
Answer: A
This is the long-term mechanism — changes in the amount of enzyme, which take hours (Unit 7 §6). It complements the two rapid mechanisms, covalent modification and allosteric effects, which act within seconds.TMU Lecture 12b Slide 11
19The normal concentration of blood glucose is ( ).
Answer: B
Regulated within narrow limits. Blood glucose is derived from the diet, gluconeogenesis and glycogenolysis, and is used by oxidation, glycogen synthesis, the pentose phosphate pathway, amino acid synthesis and adipose tissue.TMU Lecture 12b Slide 18
20Blood glucose is derived from which three sources?
Answer: C
And its fates are: oxidation, glycogen, the pentose phosphate pathway, amino acids, and adipose tissue. Note that glycolysis and lipogenesis are uses, not sources — a common confusion in this MCQ.TMU Lecture 12b Slide 18
21Glucokinase is important in regulating blood glucose after a meal because ( ).
Answer: D
Unit 10's Km distinction, doing physiology. Hexokinase (low Km) keeps every tissue supplied at all times; glucokinase (high Km, liver and pancreatic β cells) engages only after a meal — removing glucose from the blood and providing G6P for glycogen synthesis and lipogenesis.TMU Lecture 12b Slide 19 · Harper's ch.17, p.170
22Gluconeogenesis is important in maintaining citric acid cycle intermediates because ( ).
Answer: E
This is the biochemical basis of “fat burns in the flame of carbohydrate”. In starvation, oxaloacetate is drained into gluconeogenesis, so acetyl-CoA from fat arrives with no partner to condense with and is diverted to ketone bodies (Unit 17). Starvation ketosis is the arithmetic of oxaloacetate.TMU Lecture 12b Slide 5 · Harper's ch.16, pp.164–165
23Which hormone opposes the actions of insulin on blood glucose?
Answer: A
Insulin plays a central role in regulating blood glucose; glucagon opposes its actions. Other hormones that affect blood glucose include epinephrine, glucocorticoids, growth hormone and thyroid hormones.TMU Lecture 12b Slide 19
24Hypoglycaemia is dangerous principally because ( ).
Answer: B
The brain has a substantial requirement for glucose and cannot substitute fatty acids. That single dependence is why gluconeogenesis exists, why PDH is inhibited in starvation to spare carbohydrate, and why glycolytic and PDH defects present neurologically.TMU Lecture 12b Slide 5
25In the FED state, which combination is correct?
Answer: C
Insulin raises phosphodiesterase activity → cAMP falls → enzymes are dephosphorylated → glycogen synthase on, phosphorylase off; PFK-2 makes fructose 2,6-bisphosphate → glycolysis on, gluconeogenesis off. Store and burn. Units 10, 12 and 13 are one system with a switch.Harper's ch.19, p.190 · Harper's ch.18, p.180
1 Gluconeogenesis — 3′+
The term used to include all pathways responsible for converting non-carbohydrate precursors to glucose or glycogen.
The major substrates are the glucogenic amino acids, lactate, glycerol and propionate; the major gluconeogenic tissues are liver and kidney.
It uses the reversible reactions of glycolysis plus four additional enzymes that circumvent the three irreversible non-equilibrium steps: pyruvate carboxylase and PEP carboxykinase (bypassing pyruvate kinase), fructose 1,6-bisphosphatase (bypassing PFK-1), and glucose-6-phosphatase (bypassing hexokinase/glucokinase).
It meets the body's need for glucose when carbohydrate is unavailable from the diet or from glycogen reserves, and clears lactate produced by muscle and erythrocytes and glycerol produced by adipose tissue.TMU Lecture 12b Slide 3 · Harper's ch.19, pp.184–186
The major substrates are the glucogenic amino acids, lactate, glycerol and propionate; the major gluconeogenic tissues are liver and kidney.
It uses the reversible reactions of glycolysis plus four additional enzymes that circumvent the three irreversible non-equilibrium steps: pyruvate carboxylase and PEP carboxykinase (bypassing pyruvate kinase), fructose 1,6-bisphosphatase (bypassing PFK-1), and glucose-6-phosphatase (bypassing hexokinase/glucokinase).
It meets the body's need for glucose when carbohydrate is unavailable from the diet or from glycogen reserves, and clears lactate produced by muscle and erythrocytes and glycerol produced by adipose tissue.TMU Lecture 12b Slide 3 · Harper's ch.19, pp.184–186
2 Fructose 2,6-bisphosphate — 3′+
The most potent positive allosteric effector of phosphofructokinase-1 and inhibitor of fructose-1,6-bisphosphatase in liver — a single molecule exerting opposite effects on the key enzymes of glycolysis and gluconeogenesis.
It is formed by phosphorylation of fructose 6-phosphate by phosphofructokinase-2; the same enzyme protein is also responsible for its breakdown, since it has fructose-2,6-bisphosphatase activity — a bifunctional enzyme whose activity is switched by cAMP-dependent phosphorylation.
⚠️ It is a regulatory signal only, not an intermediate of the glycolytic pathway — unlike fructose 1,6-bisphosphate.Harper's ch.19, pp.188–189
It is formed by phosphorylation of fructose 6-phosphate by phosphofructokinase-2; the same enzyme protein is also responsible for its breakdown, since it has fructose-2,6-bisphosphatase activity — a bifunctional enzyme whose activity is switched by cAMP-dependent phosphorylation.
⚠️ It is a regulatory signal only, not an intermediate of the glycolytic pathway — unlike fructose 1,6-bisphosphate.Harper's ch.19, pp.188–189
3 The Cori cycle — 2′+
The cycle in which lactate produced by anaerobic glycolysis in muscle and erythrocytes is carried in the blood to the liver, reconverted to glucose by gluconeogenesis, and returned to the muscle.
It is energetically expensive for the liver, which must supply the ATP and GTP for gluconeogenesis. The resulting increase in oxygen consumption appears as the oxygen debt after vigorous exercise, and the same mechanism underlies the hypermetabolism of septic shock and cancer cachexia.Harper's ch.19, p.191
It is energetically expensive for the liver, which must supply the ATP and GTP for gluconeogenesis. The resulting increase in oxygen consumption appears as the oxygen debt after vigorous exercise, and the same mechanism underlies the hypermetabolism of septic shock and cancer cachexia.Harper's ch.19, p.191
4 Reciprocal regulation of glycolysis and gluconeogenesis — 3′+
Because glycolysis and gluconeogenesis share the same pathway but operate in opposite directions, their activities are regulated reciprocally — otherwise the cell would run both simultaneously in a futile cycle consuming ATP.
Three mechanisms operate: changes in the rate of enzyme synthesis (induction and repression, taking hours); covalent modification by reversible phosphorylation — glucagon raises cAMP, activating cAMP-dependent protein kinase, which phosphorylates and inactivates pyruvate kinase; and allosteric effects, chiefly through fructose 2,6-bisphosphate.TMU Lecture 12b Slides 10, 14, 24
Three mechanisms operate: changes in the rate of enzyme synthesis (induction and repression, taking hours); covalent modification by reversible phosphorylation — glucagon raises cAMP, activating cAMP-dependent protein kinase, which phosphorylates and inactivates pyruvate kinase; and allosteric effects, chiefly through fructose 2,6-bisphosphate.TMU Lecture 12b Slides 10, 14, 24
1
Outline briefly the pathway of gluconeogenesis and how it is regulated reciprocally with glycolysis.
5′ — 'outline briefly'
Definition and importance
Gluconeogenesis includes all pathways responsible for converting non-carbohydrate precursors to glucose or glycogen. The major substrates are the glucogenic amino acids, lactate, glycerol and propionate, and the major tissues are liver and kidney.
It meets the needs of the body for glucose when carbohydrate is not available in sufficient amounts from the diet or from glycogen reserves — liver glycogen being almost exhausted after 12–18 hours. Hypoglycaemia causes brain dysfunction, which can lead to coma and death. It also clears lactate produced by muscle and erythrocytes and glycerol produced by adipose tissue, and maintains the level of citric acid cycle intermediates when fatty acids are the main source of acetyl-CoA.
The pathway
Gluconeogenesis involves glycolysis, the citric acid cycle, and some special reactions. Seven glycolytic steps are freely reversible; three non-equilibrium reactions prevent simple reversal and require four bypass enzymes:
| Irreversible glycolytic step | Bypass |
|---|---|
| Pyruvate → phosphoenolpyruvate (pyruvate kinase) | Pyruvate carboxylase — mitochondrial, requires ATP and biotin, forming oxaloacetate; then PEP carboxykinase, using GTP |
| Fructose 1,6-bisphosphate → fructose 6-phosphate (PFK-1) | Fructose 1,6-bisphosphatase |
| Glucose 6-phosphate → glucose (hexokinase/glucokinase) | Glucose-6-phosphatase — liver and kidney only |
The first bypass requires two enzymes because the fall from PEP to pyruvate is the largest free-energy change in glycolysis; the decarboxylation by PEP carboxykinase is what makes the phosphorylation energetically feasible.
Reciprocal regulation
Since glycolysis and gluconeogenesis share the same pathway but operate in opposite directions, their activities are regulated reciprocally. Three mechanisms operate:
- Changes in the rate of enzyme synthesis. The enzymes of glucose utilisation become more active when there is a superfluity of glucose, while the gluconeogenic enzymes have low activity. This takes hours.
- Covalent modification. Glucagon, and to a lesser extent epinephrine, respond to a fall in blood glucose by increasing cAMP, activating cAMP-dependent protein kinase, which phosphorylates and inactivates pyruvate kinase.
- Allosteric effects. Chiefly through fructose 2,6-bisphosphate, the most potent positive allosteric effector of PFK-1 and inhibitor of fructose-1,6-bisphosphatase. It is made and destroyed by the same bifunctional enzyme (PFK-2 / fructose-2,6-bisphosphatase), whose activity is switched by cAMP-dependent phosphorylation. Glucagon therefore lowers fructose 2,6-bisphosphate, switching the liver from glycolysis to gluconeogenesis in a single step.
Marking guide: definition with substrates and tissues 1 · reason gluconeogenesis is needed 0.5 · the three irreversible steps identified 0.5 · four bypass enzymes named correctly 1.5 · statement of reciprocal regulation with the three mechanisms 1 · fructose 2,6-bisphosphate and the bifunctional enzyme 0.5.
2
Elucidate the regulation of blood glucose concentration.
8′ — 'elucidate'
The set point
The concentration of blood glucose is regulated within narrow limits — 3.89–6.11 mmol/L. This matters because the brain depends on glucose as a fuel, and hypoglycaemia causes brain dysfunction, which can lead to coma and death.
Sources and fates
| Derived from | Used by |
|---|---|
| The diet Gluconeogenesis Glycogenolysis | Oxidation (glycolysis) Glycogen synthesis The pentose phosphate pathway Amino acid synthesis Adipose tissue — lipogenesis |
The fed state
After a meal, portal glucose is high. Glucokinase is important in regulating blood glucose after a meal: its much higher Km than hexokinase means it engages only when glucose is abundant, allowing the liver to remove the surplus and provide glucose 6-phosphate in excess of the requirements for glycolysis, for glycogen synthesis and lipogenesis. In the pancreas, the glucose 6-phosphate formed by glucokinase signals increased glucose availability and leads to the secretion of insulin.
Insulin plays a central role. In liver it increases the activity of phosphodiesterase, lowering cAMP. The enzymes of carbohydrate metabolism are therefore dephosphorylated: glycogen synthase is activated and phosphorylase inactivated; PFK-2 acts as a kinase, so fructose 2,6-bisphosphate rises, activating PFK-1 and inhibiting fructose-1,6-bisphosphatase. Glycolysis and glycogenesis proceed; gluconeogenesis is suppressed.
The fasting state
Glucagon opposes the actions of insulin. Responding to a fall in blood glucose, it increases cAMP, activating cAMP-dependent protein kinase, so the enzymes become phosphorylated.
- Glycogen: phosphorylase kinase then phosphorylase are activated (b → a) while glycogen synthase is inactivated — glycogenolysis. Since only liver and kidney possess glucose-6-phosphatase, only they can export the glucose.
- Glycolysis: pyruvate kinase is phosphorylated and inactivated.
- Fructose 2,6-bisphosphate: the bifunctional enzyme switches to phosphatase mode, so the concentration falls — PFK-1 loses its activator, fructose-1,6-bisphosphatase loses its inhibitor, and gluconeogenesis proceeds.
After 12–18 hours liver glycogen is almost totally depleted, and gluconeogenesis becomes the sole source of endogenous glucose.
Longer-term and other influences
Induction and repression of key enzyme synthesis provides the slow, adaptive layer: the enzymes of glucose utilisation become more active when glucose is plentiful, while the gluconeogenic enzymes have low activity. Other hormones — epinephrine, glucocorticoids, growth hormone and thyroid hormones — also affect blood glucose.
Marking guide: normal range quoted 0.5 · three sources and at least three fates 1.5 · glucokinase's role after a meal explained by its Km 1.5 · insulin's actions including phosphodiesterase and dephosphorylation 1.5 · glucagon's actions on glycogen, pyruvate kinase and fructose 2,6-bisphosphate 2 · the 12–18 hour glycogen limit, or enzyme induction, or other hormones 1.