Unit 22 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
1The first priority of metabolism in every nutritional state is ( ).
Answer: C
The blood glucose level must be maintained above 2.2 mmol/L. The brain uses glucose almost exclusively and cannot use fatty acids, which are albumin-bound and cannot cross the blood-brain barrier; the erythrocyte has no mitochondria and has no alternative at all. Everything else in this unit is machinery for defending that number.TMU Lecture 18 slides 7, 12
2The master signal governing the fed-to-fasting transition is ( ).
Answer: D
It is the ratio the tissues read, not either hormone alone. A high ratio indicates that fuel storage is taking place; a low ratio means mobilisation. “When glucagon speaks, the liver listens.”TMU Lecture 18 slides 4, 8
3Glucokinase is adapted to the fed liver because ( ).
Answer: E
It therefore phosphorylates glucose only at concentrations well above the fasting level of 5 mM — like those in the hepatic portal vein after a meal, about 22 mM. Option A describes hexokinase, whose low Km keeps peripheral uptake constant. The kinetics ARE the physiological role — Unit 6 doing physiology.TMU Lecture 18 slides 4–5 · Harper's ch.17
4Muscle glycogen cannot raise the blood glucose concentration because muscle lacks ( ).
Answer: A
Skeletal muscle donates amino acids for gluconeogenesis in the liver, but it keeps its glycogen to itself. Muscle carbon reaches the blood only as lactate (Cori cycle) or alanine (glucose-alanine cycle), and both require the liver to convert them back. Only liver and kidney have glucose-6-phosphatase.Harper's ch.19 · TMU Lecture 18 slide 11
5Adipose tissue cannot reuse the glycerol released by lipolysis because it lacks ( ).
Answer: B
The glycerol therefore passes to the liver, which does have the enzyme. A consequence worth stating in an exam: the adipocyte must make glycerol-3-phosphate from glucose by glycolysis, so fat storage depends on a supply of glucose — and hence on insulin. That is exactly why lipolysis runs unopposed in untreated diabetes.Harper's ch.24 · Harper's ch.25, p.262
6In the fed state, insulin acts on adipose tissue by ( ).
Answer: C
Two lipases, opposite jobs, opposite control. Lipoprotein lipase brings fat INTO the adipocyte from chylomicrons and VLDL; hormone-sensitive lipase lets it OUT. Insulin is the principal antilipolytic hormone. Option E is the glucagon/epinephrine action, not insulin's.Harper's ch.25, pp.256, 262–263
7During fasting, glucagon promotes gluconeogenesis principally by ( ).
Answer: D
Fructose 2,6-bisphosphate is the reciprocal switch of Unit 13 — it activates PFK-1 and inhibits fructose 1,6-bisphosphatase simultaneously, so lowering it turns glycolysis off and gluconeogenesis on with one signal. Glucagon simultaneously activates glycogen phosphorylase while glycogen synthase is inhibited.TMU Lecture 18 slide 8 · Harper's ch.19–20
8How does fatty acid oxidation in the fasting liver promote gluconeogenesis?
Answer: E
Note the elegance: fatty acids contribute no carbon whatsoever — pyruvate dehydrogenase is irreversible — yet they make gluconeogenesis possible. They signal, they fund, and they spare glucose in every tissue that burns them. The fat is the fuel; the amino acids and glycerol are the carbon.TMU Lecture 18 slides 9–10
9Which amino acids are NOT released from muscle into the bloodstream during fasting?
Answer: A
Because the branched-chain α-ketoacid dehydrogenase complex is absent from the liver, these three are oxidised where they are (Unit 20). All other amino acids are transported to the liver for transamination and use in gluconeogenesis. Option B names the two principal exported carriers — the opposite of what is asked.TMU Lecture 18 slide 11 · Harper's ch.28
10The two aims of the metabolic adaptation to starvation are ( ).
Answer: B
Protein-sparing is the whole point, because there is no protein store — every gram degraded is functioning tissue lost. The evidence is in the numbers: muscle-protein degradation falls from 75 g/day on day 3 to 20 g/day on day 40.TMU Lecture 18 slides 12, 15
11Between day 3 and day 40 of starvation, brain glucose consumption and brain ketone body consumption change from ( ).
Answer: C
The brain has switched fuel, not reduced consumption. Option D is the liver output row and option E mixes the muscle-protein and lipolysis rows — read the table by row, not by number. Every gram of glucose the brain stops demanding is muscle the liver does not have to dismantle.TMU Lecture 18 slide 15
12In the starvation fuel table, which figure is UNCHANGED between day 3 and day 40?
Answer: D
Fat is the one store deep enough not to need rationing — it is drawn on at a constant rate throughout, which is why survival time in starvation is set by the size of the fat depot. Note that liver ketone body output is also unchanged at 150, while glucose output halves: the liver has not slowed down, it has changed product.TMU Lecture 18 slide 15
13Ketone body production rises in starvation because ( ).
Answer: E
“Fat burns in the flame of carbohydrate.” Gluconeogenesis slows down; free fatty acids continue to be mobilized from adipose tissue and the oxidation of fatty acids continues unabated — so the acetyl-CoA has nowhere to go but ketogenesis. Note option D has the direction backwards: the liver makes them and the periphery consumes them, because the liver lacks the CoA transferase.TMU Lecture 18 slides 13–14 · Harper's ch.22
14Untreated diabetes mellitus is said to resemble starvation because ( ).
Answer: A
Starvation in the midst of plenty. A low insulin/glucagon ratio results eventually in hyperglycemia, muscle wasting and ketosis, and the hepatic output of glucose is increased because of stimulation of glycogenolysis and gluconeogenesis — the liver adds glucose to a bloodstream already overloaded, because the signal it is reading says “fasting”.TMU Lecture 18 slides 16–17
15Why is ketogenesis in untreated diabetes faster than in starvation?
Answer: B
Two differences, and Harper's-level answers name both. In starvation insulin is low but not absent, so the antilipolytic brake is still partly applied; in type 1 diabetes there is none. And in starvation the brain adapts and consumes ketone bodies, whereas in diabetes it does not. Production maximal, consumption not — hence ketoacidosis, since these are relatively strong acids.TMU Lecture 18 slide 17
16Diabetics show elevated chylomicrons and VLDL chiefly because ( ).
Answer: C
Insulin normally induces lipoprotein lipase in adipose tissue; without it the enzyme is not made, so triacylglycerol-rich particles are not cleared. Note the compounding effect: the absence of insulin also causes adipose tissue to take up too little glucose, contributing to higher blood glucose levels. Option D is familial hypercholesterolemia.TMU Lecture 18 slide 18
17Muscle wasting occurs in untreated diabetes because ( ).
Answer: D
Skeletal muscle needs insulin to keep proteins from being degraded. Add that the lack of insulin prevents glucose uptake, causing reliance on muscle glycogen stores, and the clinical triad of hyperglycemia, muscle wasting and ketosis is fully accounted for.TMU Lecture 18 slide 19
18A 100-metre sprint is powered by ( ).
Answer: E
The organising principle: the faster you need ATP, the less efficient the pathway you must use. Part of the ATP consumed in a 1000-metre run must come from oxidative phosphorylation, and a marathon is characterized by cooperation between muscle, liver and adipose tissue. “Hitting the wall” is hepatic glycogen depletion — and its symptoms are cerebral.TMU Lecture 18 slide 21
19Leptin is ( ).
Answer: A
During the starved state, adipose tissue loses mass, the secretion of both leptin and insulin declines, and fuel utilization is increased. Mice lacking leptin are obese and will lose weight if given leptin — but note that most obese humans have high leptin. A hormone deficiency and a hormone resistance can produce the same phenotype and demand opposite treatments.TMU Lecture 18 slide 20
20Obesity is a risk factor for all of the following EXCEPT ( ).
Answer: B
Type 1 diabetes is an autoimmune destruction of the β cells — an absolute insulin deficiency, unrelated to fat mass. The listed associations are with diabetes mellitus (type 2), hypertension and cardiovascular disease, all mediated through insulin resistance.TMU Lecture 18 slide 20
21Ethanol alters hepatic metabolism principally because ( ).
Answer: C
Ethanol + NAD⁺ → acetaldehyde + NADH + H⁺, then acetaldehyde + NAD⁺ + H₂O → acetate + NADH + H⁺. Ethanol has no receptor in this story — it causes disease by chemistry, dumping reducing equivalents into the liver.TMU Lecture 18 slide 22
22Alcoholic hypoglycemia occurs because the raised NADH/NAD⁺ ratio ( ).
Answer: D
Both enzymes need NAD⁺, so with NADH high the equilibria shift away from pyruvate and oxaloacetate. It is worst in someone who has not eaten, whose glycogen is already gone. The same shift causes lactic acidosis, which raises the renal threshold for urate — hence alcohol-precipitated gout.TMU Lecture 18 slide 22 · Harper's ch.25, p.265
23Which molecule links the regulation of fatty acid synthesis to that of fatty acid oxidation?
Answer: E
The first committed intermediate of synthesis is the inhibitor of CPT-I, the gateway to oxidation. Compare the parallel switches this course keeps returning to: fructose 2,6-bisphosphate for glycolysis/gluconeogenesis, cAMP-driven phosphorylation for glycogen, acetyl-CoA for pyruvate dehydrogenase versus pyruvate carboxylase.Harper's ch.22, p.229 · Harper's ch.23
24In the fed state the liver disposes of surplus glucose by all of the following EXCEPT ( ).
Answer: A
Gluconeogenesis makes glucose; in the fed state it is switched off. High insulin/glucagon increases the activity of glycogen synthase and pyruvate dehydrogenase, so glucose goes to glycogen and the surplus onward to fatty acids and VLDL. The pentose phosphate pathway supplies the NADPH that lipogenesis consumes — 14 per palmitate.TMU Lecture 18 slides 4–5 · Harper's ch.23
25Which organ is correctly matched with its preferred fuel?
Answer: B
Correcting the others: the brain cannot use fatty acids at all; the erythrocyte has no mitochondria, so glucose only, in every state; except for short elevations in energy demand, the preferential fuel for muscle is fat; and the liver cannot use the ketone bodies it makes, lacking succinyl-CoA-acetoacetate CoA transferase.Harper's ch.14 · Harper's ch.22, p.230
1 The well-fed (absorptive) state — 3′+
The metabolic state following a meal, in which the ratio of insulin to glucagon is high, indicating that fuel storage is taking place.
Liver: glucokinase traps large influxes of glucose from the hepatic portal vein — its Km of 10 mM (against 0.1 mM for hexokinase) means it works only above the fasting level of 5 mM, and unlike hexokinase it is not inhibited by glucose 6-phosphate. High insulin/glucagon increases the activity of glycogen synthase and pyruvate dehydrogenase, so glucose goes to glycogen, and the surplus to acetyl-CoA, fatty acids and VLDL.
Muscle: insulin increases glycogen synthase activity and protein synthesis. Except for short elevations in energy demand, the preferential fuel for muscle is fat.
Adipose tissue: insulin induces lipoprotein lipase and inhibits hormone-sensitive lipase; glucose uptake supplies glycerol-3-phosphate for esterification.
Brain: burns glucose, as always.TMU Lecture 18 slides 4–7
Liver: glucokinase traps large influxes of glucose from the hepatic portal vein — its Km of 10 mM (against 0.1 mM for hexokinase) means it works only above the fasting level of 5 mM, and unlike hexokinase it is not inhibited by glucose 6-phosphate. High insulin/glucagon increases the activity of glycogen synthase and pyruvate dehydrogenase, so glucose goes to glycogen, and the surplus to acetyl-CoA, fatty acids and VLDL.
Muscle: insulin increases glycogen synthase activity and protein synthesis. Except for short elevations in energy demand, the preferential fuel for muscle is fat.
Adipose tissue: insulin induces lipoprotein lipase and inhibits hormone-sensitive lipase; glucose uptake supplies glycerol-3-phosphate for esterification.
Brain: burns glucose, as always.TMU Lecture 18 slides 4–7
2 The fasting state — 3′+
The state beginning about 3 to 32–36 hours after a meal, in which the ratio of insulin to glucagon falls because the blood sugar concentration falls. “When glucagon speaks, the liver listens.”
Glycogen: glucagon activates glycogen phosphorylase; glycogen synthase is inhibited.
Gluconeogenesis: glucagon lowers fructose 2,6-bisphosphate, removing the inhibitor of fructose 1,6-bisphosphatase.
Adipose tissue: progressive release of alanine from muscle and mobilization of free fatty acids and glycerol.
How fat drives gluconeogenesis: hepatic FFA oxidation raises acetyl-CoA and hence citrate, which stimulates fructose 1,6-bisphosphatase; acetyl-CoA stimulates pyruvate carboxylase → oxaloacetate → PEP; and it increases citric acid cycle activity, raising ATP, which inhibits glycolysis. Fatty acids supply no carbon to glucose but signal, fund and spare.
Muscle donates amino acids for hepatic gluconeogenesis but keeps its glycogen to itself; the branched-chain amino acids are transaminated locally and not released.TMU Lecture 18 slides 8–11
Glycogen: glucagon activates glycogen phosphorylase; glycogen synthase is inhibited.
Gluconeogenesis: glucagon lowers fructose 2,6-bisphosphate, removing the inhibitor of fructose 1,6-bisphosphatase.
Adipose tissue: progressive release of alanine from muscle and mobilization of free fatty acids and glycerol.
How fat drives gluconeogenesis: hepatic FFA oxidation raises acetyl-CoA and hence citrate, which stimulates fructose 1,6-bisphosphatase; acetyl-CoA stimulates pyruvate carboxylase → oxaloacetate → PEP; and it increases citric acid cycle activity, raising ATP, which inhibits glycolysis. Fatty acids supply no carbon to glucose but signal, fund and spare.
Muscle donates amino acids for hepatic gluconeogenesis but keeps its glycogen to itself; the branched-chain amino acids are transaminated locally and not released.TMU Lecture 18 slides 8–11
3 Starvation — 3′+
The prolonged fasted state, whose adaptations show an attempt by the body to conserve blood glucose and to spare PROTEIN from continual degradation. The blood glucose level must be maintained above 2.2 mM, and the first priority is to provide sufficient glucose to the brain and red blood cells.
Gluconeogenesis slows down; free fatty acids continue to be mobilized and the oxidation of fatty acids continues unabated, so oxaloacetate is drawn into gluconeogenesis and the surplus acetyl-CoA is converted to ketone bodies. As starvation progresses, muscle increases its reliance on free fatty acids and spares ketones for use by the brain.
The fuel table (g/24 h), day 3 → day 40:
• Brain glucose 100 → 40; brain ketone bodies 50 → 100
• Muscle-protein degradation 75 → 20 — the protein-sparing effect
• Adipose lipolysis 180 → 180, unchanged
• Liver glucose output 150 → 80; liver ketone bodies 150 → 150TMU Lecture 18 slides 12–15
Gluconeogenesis slows down; free fatty acids continue to be mobilized and the oxidation of fatty acids continues unabated, so oxaloacetate is drawn into gluconeogenesis and the surplus acetyl-CoA is converted to ketone bodies. As starvation progresses, muscle increases its reliance on free fatty acids and spares ketones for use by the brain.
The fuel table (g/24 h), day 3 → day 40:
• Brain glucose 100 → 40; brain ketone bodies 50 → 100
• Muscle-protein degradation 75 → 20 — the protein-sparing effect
• Adipose lipolysis 180 → 180, unchanged
• Liver glucose output 150 → 80; liver ketone bodies 150 → 150TMU Lecture 18 slides 12–15
4 The metabolic picture of untreated diabetes mellitus — 3′+
Untreated diabetes resembles starvation in several ways — without insulin the tissues cannot take up glucose and behave as though there were none, despite hyperglycemia.
A low insulin/glucagon ratio results eventually in hyperglycemia, muscle wasting and ketosis.
Liver: hepatic output of glucose is increased because of stimulation of glycogenolysis and gluconeogenesis. The increased supply of FFA to the liver, combined with the removal of oxaloacetate by the gluconeogenic pathway, shunts excessive amounts of acetyl-CoA into the production of ketone bodies — at a rate much greater than is seen in starvation.
Adipose tissue: the low ratio signals fasting, so lipolysis is unopposed; reduced lipoprotein lipase activity causes elevation of chylomicrons and VLDL; and too little glucose is taken up.
Muscle: skeletal muscle needs insulin to keep proteins from being degraded; without it, protein synthesis is decreased and degradation is increased.TMU Lecture 18 slides 16–19
A low insulin/glucagon ratio results eventually in hyperglycemia, muscle wasting and ketosis.
Liver: hepatic output of glucose is increased because of stimulation of glycogenolysis and gluconeogenesis. The increased supply of FFA to the liver, combined with the removal of oxaloacetate by the gluconeogenic pathway, shunts excessive amounts of acetyl-CoA into the production of ketone bodies — at a rate much greater than is seen in starvation.
Adipose tissue: the low ratio signals fasting, so lipolysis is unopposed; reduced lipoprotein lipase activity causes elevation of chylomicrons and VLDL; and too little glucose is taken up.
Muscle: skeletal muscle needs insulin to keep proteins from being degraded; without it, protein synthesis is decreased and degradation is increased.TMU Lecture 18 slides 16–19
1
Describe the metabolic responses to the well-fed state, fasting and starvation.
10′
The problem being solved
The first priority of metabolism is to provide sufficient glucose to the brain and red blood cells, and the blood glucose level must be maintained above 2.2 mmol/L. The brain uses glucose almost exclusively and cannot oxidise fatty acids; the erythrocyte has no mitochondria at all. Every adaptation below defends that supply. The master signal throughout is the RATIO of insulin to glucagon.
The well-fed state
The ratio of insulin to glucagon is high, indicating that fuel storage is taking place.
- Liver. Glucokinase is adapted to trap large influxes of glucose from the hepatic portal vein. Its Km is 10 mM against 0.1 mM for hexokinase, so it works only above the fasting level of 5 mM — like the ~22 mM of the portal vein after a meal — and unlike hexokinase it is not inhibited by glucose 6-phosphate. High insulin/glucagon increases glycogen synthase and pyruvate dehydrogenase activity, so glucose becomes glycogen, and the surplus acetyl-CoA becomes fatty acids exported as VLDL.
- Muscle. Insulin increases glycogen synthase activity and protein synthesis. Except for short elevations in energy demand, the preferential fuel for muscle is fat.
- Adipose tissue. Insulin induces lipoprotein lipase and inhibits hormone-sensitive lipase; glucose supplies glycerol-3-phosphate, since the adipocyte lacks glycerol kinase.
Fasting
Beginning 3 to 32–36 hours after a meal, the insulin/glucagon ratio falls because the blood sugar concentration falls.
- Glucagon activates glycogen phosphorylase while glycogen synthase is inhibited.
- Glucagon lowers fructose 2,6-bisphosphate, removing the inhibitor of fructose 1,6-bisphosphatase, so gluconeogenesis proceeds.
- Progressive release of alanine from muscle and mobilization of free fatty acids and glycerol.
How fat drives the process: hepatic FFA oxidation raises acetyl-CoA → citrate → stimulation of fructose 1,6-bisphosphatase; acetyl-CoA stimulates pyruvate carboxylase → oxaloacetate → PEP; and acetyl-CoA increases citric acid cycle activity, raising ATP, which inhibits glycolysis. Fatty acids contribute no carbon to glucose — pyruvate dehydrogenase is irreversible — but they signal, fund and spare. The fat is the fuel; the amino acids and glycerol are the carbon.
Muscle donates amino acids for gluconeogenesis but keeps its glycogen to itself, having no glucose-6-phosphatase; the branched-chain amino acids are transaminated to α-ketoacids locally rather than released.
Starvation
The aims are explicit: to conserve blood glucose and to spare protein from continual degradation.
Gluconeogenesis slows down; free fatty acids continue to be mobilized and fatty acid oxidation continues unabated, so with oxaloacetate diverted into gluconeogenesis the acetyl-CoA overflows into ketone bodies. Muscle increases its reliance on free fatty acids and spares ketones for use by the brain, and the brain defers to the red blood cells in the consumption of glucose.
| g / 24 h | Day 3 | Day 40 |
|---|---|---|
| Brain — glucose | 100 | 40 |
| Brain — ketone bodies | 50 | 100 |
| Adipose lipolysis | 180 | 180 |
| Muscle-protein degradation | 75 | 20 |
| Liver — glucose out | 150 | 80 |
| Liver — ketone bodies out | 150 | 150 |
Read as one argument: the brain has switched fuel rather than reduced consumption; the payoff is that muscle-protein degradation falls from 75 to 20 g/day; fat is drawn on at a constant rate throughout, so survival time is set by the size of the fat depot; and some glucose must always be made, because the erythrocyte has no alternative. Ketone bodies exist to spare protein.
Marking guide: the priority of brain and erythrocyte glucose 1 · insulin/glucagon ratio as master signal 0.5 · glucokinase kinetics 1.5 · fed-state changes in three tissues 2 · fasting switches, with fructose 2,6-bisphosphate named 1.5 · how fat oxidation drives gluconeogenesis 1.5 · the starvation figures, at least three rows 1.5 · the protein-sparing conclusion 0.5.
2
Compare the metabolic state of untreated diabetes mellitus with that of starvation.
8′
The resemblance, and its cause
Untreated diabetes resembles starvation in several ways. The reason is that without insulin the tissues cannot take up glucose and therefore behave exactly as though there were none — whatever the blood concentration. It is starvation in the midst of plenty: the signals the tissues receive say “fasting”, and they respond accordingly.
| Starvation | Untreated diabetes | |
|---|---|---|
| Blood glucose | Low-normal | HIGH |
| Insulin | Low but present | Absent or ineffective |
| Hepatic glucose output | Appropriate | Inappropriately increased |
| Lipolysis | High but restrained by residual insulin | Completely unopposed |
| Ketogenesis | High; ketone bodies consumed by brain and muscle | Much greater; not consumed → ketoacidosis |
| Muscle protein | Spared as adaptation proceeds | Wasting |
| Purpose | Adaptive — protects the brain | Maladaptive — no shortage exists |
Organ by organ in diabetes
- Liver. Hepatic output of glucose is increased because of stimulation of glycogenolysis and gluconeogenesis — this leads to hyperglycemia. The increased supply of FFA, combined with the removal of oxaloacetate by the gluconeogenic pathway, shunts excessive amounts of acetyl-CoA into the production of ketone bodies, at a rate much greater than is seen in starvation.
- Adipose tissue. The low insulin/glucagon ratio signals fasting, so FFA mobilization is a normal response to the glucagon signal, especially when insulin is low. Diabetics have reduced lipoprotein lipase activity, causing an elevation in chylomicrons and VLDL, and the absence of insulin causes adipose tissue to take up too little glucose, contributing to higher blood glucose levels.
- Skeletal muscle. Skeletal muscle needs insulin to keep proteins from being degraded. The lack of insulin prevents glucose uptake, causing reliance on muscle glycogen stores and increased blood glucose level. Protein synthesis is decreased and degradation is increased — hence the wasting.
Why diabetic ketoacidosis, and not mere ketosis
Both states divert oxaloacetate into gluconeogenesis and overflow acetyl-CoA into ketogenesis, so the pathway is the same. Two differences make the outcome different.
First, the brake. Insulin is the principal antilipolytic hormone. In starvation it is low but present, and lipolysis remains restrained; in type 1 diabetes there is none at all, and free fatty acid delivery to the liver is enormous.
Second, the consumer. In starvation glucose is scarce, so the brain adapts and burns ketone bodies — up to 100 g/day by day 40. In diabetes blood glucose is high and no such adaptation occurs, so the ketone bodies accumulate. Production is maximal and consumption is not.
Since acetoacetate and 3-hydroxybutyrate are relatively strong acids, the result is ketoacidosis rather than the harmless ketosis of fasting.
The summary sentence
In starvation the metabolic response is appropriate to a real shortage; in diabetes an identical response is mounted against a shortage that does not exist, and the hyperglycemia and acidosis are the price.
Marking guide: the resemblance stated with its cause 1.5 · at least four correct contrasts 2 · the three tissues in diabetes 2 · the two reasons ketogenesis exceeds that of starvation 2 · a closing statement of adaptive vs maladaptive 0.5.