Unit 17 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
1Fatty acids are activated before oxidation by ( ).
Answer: C
ATP is converted to AMP and PPi, and the PPi is then hydrolysed by inorganic pyrophosphatase — a loss of a further ~P, ensuring that the overall reaction goes to completion. Two high-energy phosphates spent to start; this is why the net yield of palmitate oxidation is 106 and not 108.Harper's ch.22, p.227
2Long-chain acyl-CoA cannot penetrate the inner mitochondrial membrane. It is carried across ( ).
Answer: D
Carnitine (β-hydroxy-γ-trimethylammonium butyrate) is widely distributed and particularly abundant in muscle. Contrast the citrate shuttle of Unit 16, which carries acetyl units OUT — carnitine carries acyl groups IN. Getting these two the wrong way round is the classic error.Harper's ch.22, p.227
3Place the three components of the carnitine shuttle in the correct order.
Answer: E
CPT-I, on the outer membrane, converts long-chain acyl-CoA to acylcarnitine. The translocase, an inner-membrane exchange transporter, takes acylcarnitine in and carnitine out. CPT-II, on the inner surface, regenerates acyl-CoA in the matrix — and carnitine is returned, so it is a catalytic carrier, not a consumed substrate.Harper's ch.22, p.227
4The rate-limiting step of fatty acid oxidation, and its principal inhibitor, are ( ).
Answer: A
This is the single most examinable fact of the unit. Malonyl-CoA is the first committed intermediate of fatty acid SYNTHESIS, so the moment the cell begins making fat it simultaneously bars the door to oxidation. One molecule enforcing reciprocal regulation across two compartments.Harper's ch.22, p.229 · Harper's ch.23
5In each cycle of β-oxidation, the reactions occur in the order ( ).
Answer: B
Learn it as ox–hyd–ox–thio. The carbon oxidised is the β-carbon, hence the name. Option E is the synthesis sequence run in the cytosol (Unit 16) — the mirror image.Harper's ch.22, p.227
6One cycle of β-oxidation of a saturated fatty acid yields ( ).
Answer: C
Using P:O ratios of 2.5 for NADH and 1.5 for FADH₂, that is 4 ATP per cycle from the reducing equivalents alone, before the acetyl-CoA is oxidised in the citric acid cycle. TMU Lecture 15 p.23 uses exactly this 1.5 + 2.5 = 4 arithmetic.Harper's ch.22, p.227 · TMU Lecture 15 p.23
7Complete oxidation of one molecule of palmitate yields how much ATP, net?
Answer: D
Seven cycles give 7 FADH₂ (10.5 ATP) + 7 NADH (17.5 ATP) = 28, plus 8 acetyl-CoA × 10 = 80 — total 108, minus 2 for activation = 106. The older 129/131 figures assume P:O of 3 and 2; this course's own Lectures 10, 11 and 15 use the modern values (see Unit 9 §7).Harper's ch.22, p.228 · TMU Lecture 15
8Oxidation of a fatty acid with an ODD number of carbon atoms yields, in the final cycle, ( ).
Answer: E
Propionyl-CoA is the only part of a fatty acid that is glucogenic. It is carboxylated to methylmalonyl-CoA (biotin) and isomerised to succinyl-CoA (vitamin B₁₂) — entering the citric acid cycle and thence gluconeogenesis. This is why B₁₂ deficiency causes methylmalonic aciduria.Harper's ch.22, p.228
9Peroxisomal β-oxidation differs from the mitochondrial pathway in that ( ).
Answer: A
Peroxisomal β-oxidation is not linked directly to phosphorylation and the generation of ATP. Its function is to shorten very long chain fatty acids (C20, C22) before they are handed to the mitochondrion. Zellweger (cerebrohepatorenal) syndrome — absence of peroxisomes — leads to accumulation of C26–C38 polyenoic acids in the brain.Harper's ch.22, p.228
10The three ketone bodies are ( ).
Answer: B
Note two points the examiner listens for. 3-hydroxybutyrate is quantitatively the predominant ketone body present in the blood and urine in ketosis — not acetoacetate. And acetone is not metabolised and is exhaled, giving the characteristic breath. Strictly, 3-hydroxybutyrate is not a ketone at all — the name is historical.Harper's ch.22, p.229
11Ketogenesis occurs in ( ).
Answer: C
Harper's is emphatic: the liver is the only organ that adds significant quantities of ketone bodies to the blood. Extrahepatic tissues consume them. This division of labour — liver makes, periphery burns — is the whole architecture of the ketone body system.Harper's ch.22, p.229
12The key regulatory enzyme of ketogenesis is ( ).
Answer: D
Distinguish the three HMG-CoA enzymes carefully. Synthase — the regulatory step of ketogenesis, mitochondrial. Lyase — cleaves HMG-CoA to acetoacetate. Reductase — the rate-limiting enzyme of cholesterol synthesis, cytosolic (Unit 19), and the statin target. Same substrate name, three different exam answers.Harper's ch.22, p.230
13Which enzyme is ABSENT from the liver, and why does that matter?
Answer: E
A beautifully economical piece of design. The liver lacks the activating enzyme, so it exports what it makes rather than consuming it. That single missing enzyme is what makes ketone bodies a fuel for other tissues instead of a futile hepatic cycle.Harper's ch.22, p.230
14During prolonged starvation, the tissue that adapts to use ketone bodies as a major fuel is ( ).
Answer: A
Ketone bodies are water-soluble and cross the blood-brain barrier, which free fatty acids — bound to albumin — cannot. This adaptation spares body protein: without it, gluconeogenesis from muscle amino acids would have to supply the brain's entire fuel demand. Options C, D and E are the obligate glycolytic tissues, which have no mitochondria or no alternative and always need glucose.Harper's ch.22, p.229
15Ketosis arises when ( ).
Answer: B
Note the phrasing — ketosis is a matter of RATE, not of a defective pathway. Mild ketonemia, ketonuria and ketotic breath occur normally in starvation, and ketosis is severe in diabetes mellitus. In uncontrolled diabetes the accompanying acid load causes ketoacidosis.Harper's ch.22, pp.230–231
16Ketogenesis is regulated at three successive stages. Which is NOT one of them?
Answer: C
Peripheral oxidation determines whether ketosis develops, but it is not one of the three hepatic control points Harper's lists. Read the three in sequence and the logic is a funnel: how much fat is released → how much enters the mitochondrion → what the acetyl-CoA is used for.Harper's ch.22, pp.229–230
17In the well-fed state, ketogenesis is low principally because ( ).
Answer: D
Both arms of the answer matter. Insulin is the principal antilipolytic hormone, cutting off the substrate supply at source; and lipogenesis is running, so malonyl-CoA is high and CPT-I is shut. Conversely in fasting, glucagon rises, lipolysis is unrestrained, malonyl-CoA falls and the gate opens.Harper's ch.22, pp.229–230
18Which statement about the relationship between fatty acid oxidation and gluconeogenesis is correct?
Answer: E
Three facts sit behind this. Pyruvate dehydrogenase is essentially irreversible, so acetyl-CoA can never become glucose; fatty acids are therefore not glucogenic, apart from the propionyl-CoA of odd-chain acids. But acetyl-CoA is the allosteric activator of pyruvate carboxylase (Unit 13), so fat oxidation funds and signals gluconeogenesis without contributing carbon to it.Harper's ch.19, p.193 · Harper's ch.22
19Carnitine deficiency presents with all of the following EXCEPT ( ).
Answer: A
The clue is the mechanism: if fatty acids cannot enter the mitochondrion, they cannot be oxidised — and ketone bodies are made from the acetyl-CoA that oxidation produces. So carnitine deficiency causes HYPOketonemia, not ketoacidosis, together with hypoglycemia because glucose cannot be spared. Treatment is oral carnitine supplementation.Harper's ch.22, p.230
20Sulfonylurea drugs such as glyburide and tolbutamide reduce fatty acid oxidation and hence ( ).
Answer: B
The logic runs back through Unit 13: block fatty acid oxidation → less acetyl-CoA → less activation of pyruvate carboxylase and less ATP to fund gluconeogenesis → less hepatic glucose output. Note that option D is the statin mechanism, an entirely different HMG-CoA enzyme.Harper's ch.22, p.229
21Which of these is the correct pairing of a disorder with its defect?
Answer: C
The correct versions of the distractors: Refsum disease is a failure of α-oxidation of phytanic acid, a branched-chain acid from dairy and ruminant fat; Zellweger is absence of peroxisomes; dicarboxylic aciduria is a lack of medium-chain acyl-CoA dehydrogenase, with nonketotic hypoglycemia; methylmalonic aciduria is B₁₂ deficiency.Harper's ch.22, pp.228, 230
22Which ketone body predominates in blood and urine in ketosis?
Answer: D
A frequently missed detail. It matters clinically too — the older nitroprusside urine test detects acetoacetate but not 3-hydroxybutyrate, so it can understate the severity of ketoacidosis, particularly when the NADH/NAD⁺ ratio is high and the equilibrium is driven towards 3-hydroxybutyrate.Harper's ch.22, p.229
23The interconversion of acetoacetate and D-3-hydroxybutyrate is catalysed by 3-hydroxybutyrate dehydrogenase and its ratio depends on ( ).
Answer: E
A worked consequence: in the fasting or diabetic liver, β-oxidation raises NADH, so the equilibrium shifts towards 3-hydroxybutyrate — which is exactly why it predominates in ketosis. The two facts are one fact.Harper's ch.22, p.229
24Acetyl-CoA formed in β-oxidation is oxidised in the citric acid cycle only when ( ).
Answer: A
Harper's states it plainly: “fat burns in the flame of carbohydrate.” The mechanism is oxaloacetate. In starvation or diabetes, oxaloacetate is diverted into gluconeogenesis, the cycle cannot accept all the acetyl-CoA arriving, and the surplus is condensed into ketone bodies instead. Ketogenesis is the overflow route.Harper's ch.22, p.229 · Harper's ch.16
25Unsaturated fatty acids require, in addition to the enzymes of β-oxidation, ( ).
Answer: B
Naturally occurring double bonds are in the cis configuration, whereas β-oxidation requires a trans intermediate; hence the isomerase. Yield note: each double bond costs about 1.5 ATP relative to the saturated acid, because the acyl-CoA dehydrogenase step is bypassed and no FADH₂ is made there.Harper's ch.22, p.228
1 β-Oxidation — 3′+
The pathway by which fatty acids are degraded two carbons at a time, occurring in the mitochondrial matrix. It is so named because oxidation occurs at the β-carbon.
The fatty acid is first activated to acyl-CoA by acyl-CoA synthetase at the cost of two high-energy phosphates, then carried across the inner membrane by the carnitine shuttle.
Each cycle comprises oxidation (FAD) → hydration → oxidation (NAD⁺) → thiolytic cleavage, yielding one acetyl-CoA, one FADH₂, one NADH and an acyl-CoA two carbons shorter.
Complete oxidation of palmitate yields 106 ATP net. Fatty acids are not glucogenic, since pyruvate dehydrogenase is irreversible — except for the propionyl-CoA from odd-chain acids.Harper's ch.22, pp.226–228
The fatty acid is first activated to acyl-CoA by acyl-CoA synthetase at the cost of two high-energy phosphates, then carried across the inner membrane by the carnitine shuttle.
Each cycle comprises oxidation (FAD) → hydration → oxidation (NAD⁺) → thiolytic cleavage, yielding one acetyl-CoA, one FADH₂, one NADH and an acyl-CoA two carbons shorter.
Complete oxidation of palmitate yields 106 ATP net. Fatty acids are not glucogenic, since pyruvate dehydrogenase is irreversible — except for the propionyl-CoA from odd-chain acids.Harper's ch.22, pp.226–228
2 The carnitine shuttle — 3′+
The transport system carrying long-chain acyl groups across the inner mitochondrial membrane, which acyl-CoA cannot itself penetrate.
Carnitine (β-hydroxy-γ-trimethylammonium butyrate) is widely distributed and particularly abundant in muscle. Three components act in sequence: CPT-I on the outer membrane forms acylcarnitine; the carnitine-acylcarnitine translocase exchanges it inwards for carnitine; CPT-II on the inner surface regenerates acyl-CoA in the matrix.
CPT-I is the rate-limiting step of fatty acid oxidation and is inhibited by malonyl-CoA, the first committed intermediate of fatty acid synthesis — the reciprocal regulation of the two pathways.
Carnitine deficiency causes hypoglycemia, hypoketonemia, and lipid accumulation with muscular weakness; it responds to oral carnitine.Harper's ch.22, pp.227, 229–230
Carnitine (β-hydroxy-γ-trimethylammonium butyrate) is widely distributed and particularly abundant in muscle. Three components act in sequence: CPT-I on the outer membrane forms acylcarnitine; the carnitine-acylcarnitine translocase exchanges it inwards for carnitine; CPT-II on the inner surface regenerates acyl-CoA in the matrix.
CPT-I is the rate-limiting step of fatty acid oxidation and is inhibited by malonyl-CoA, the first committed intermediate of fatty acid synthesis — the reciprocal regulation of the two pathways.
Carnitine deficiency causes hypoglycemia, hypoketonemia, and lipid accumulation with muscular weakness; it responds to oral carnitine.Harper's ch.22, pp.227, 229–230
3 Ketone bodies — 3′+
The collective term for acetoacetate, D-3-hydroxybutyrate and acetone, formed in the mitochondria of the liver from acetyl-CoA when fatty acid oxidation is rapid.
The liver is the only organ that adds significant quantities of ketone bodies to the blood; the regulatory enzyme is HMG-CoA synthase. 3-hydroxybutyrate is quantitatively predominant in blood and urine, and acetone is not metabolised but is exhaled.
They are water-soluble fuels that cross the blood-brain barrier, and are important substrates for heart muscle and renal cortex, and for the brain in prolonged starvation. The liver cannot use them, since it lacks succinyl-CoA-acetoacetate CoA transferase.
Ketosis results when their production exceeds the capacity of extrahepatic tissues to oxidise them.Harper's ch.22, pp.229–231 · 2019 paper, Section II
The liver is the only organ that adds significant quantities of ketone bodies to the blood; the regulatory enzyme is HMG-CoA synthase. 3-hydroxybutyrate is quantitatively predominant in blood and urine, and acetone is not metabolised but is exhaled.
They are water-soluble fuels that cross the blood-brain barrier, and are important substrates for heart muscle and renal cortex, and for the brain in prolonged starvation. The liver cannot use them, since it lacks succinyl-CoA-acetoacetate CoA transferase.
Ketosis results when their production exceeds the capacity of extrahepatic tissues to oxidise them.Harper's ch.22, pp.229–231 · 2019 paper, Section II
4 Ketogenesis — 2′+
The formation of ketone bodies from acetyl-CoA in hepatic mitochondria.
Two acetyl-CoA condense to acetoacetyl-CoA; HMG-CoA synthase — the regulatory enzyme — adds a third acetyl unit to form HMG-CoA, which HMG-CoA lyase cleaves to acetoacetate.
Regulated at three successive stages: (1) lipolysis in adipose tissue, controlling free fatty acid supply — insulin is the principal antilipolytic hormone; (2) CPT-I activity, determining the partition between oxidation and esterification; (3) the division of acetyl-CoA between ketogenesis and the citric acid cycle.Harper's ch.22, pp.229–230
Two acetyl-CoA condense to acetoacetyl-CoA; HMG-CoA synthase — the regulatory enzyme — adds a third acetyl unit to form HMG-CoA, which HMG-CoA lyase cleaves to acetoacetate.
Regulated at three successive stages: (1) lipolysis in adipose tissue, controlling free fatty acid supply — insulin is the principal antilipolytic hormone; (2) CPT-I activity, determining the partition between oxidation and esterification; (3) the division of acetyl-CoA between ketogenesis and the citric acid cycle.Harper's ch.22, pp.229–230
5 Ketosis — 2′+
The condition in which the rate of ketone body synthesis exceeds the capacity of extrahepatic tissues to oxidise them, so that they accumulate in the blood.
It manifests as ketonemia, ketonuria and a ketotic (acetone) breath. Mild ketosis occurs normally in starvation and after exercise; it is severe in diabetes mellitus, where the accompanying acid load produces ketoacidosis — acetoacetate and 3-hydroxybutyrate are relatively strong acids.Harper's ch.22, pp.230–231
It manifests as ketonemia, ketonuria and a ketotic (acetone) breath. Mild ketosis occurs normally in starvation and after exercise; it is severe in diabetes mellitus, where the accompanying acid load produces ketoacidosis — acetoacetate and 3-hydroxybutyrate are relatively strong acids.Harper's ch.22, pp.230–231
1
What are ketone bodies? Try to describe their metabolic properties.
10′ — REAL 2019 Section II question
Definition and identity
The ketone bodies are acetoacetate, D-3-hydroxybutyrate and acetone. They are water-soluble products of acetyl-CoA formed in the mitochondria of the liver when fatty acid oxidation is rapid. Strictly, 3-hydroxybutyrate is not a ketone; the name is historical.
Where they are made — and the crucial asymmetry
The liver is the only organ that adds significant quantities of ketone bodies to the blood. Extrahepatic tissues consume them. The reason for this division of labour is a single missing enzyme: the liver lacks succinyl-CoA-acetoacetate CoA transferase, the enzyme that activates acetoacetate for oxidation. The liver therefore exports what it cannot itself use — the arrangement that makes ketone bodies a fuel for the rest of the body rather than a futile hepatic cycle.
How they are formed
Two molecules of acetyl-CoA formed in β-oxidation condense to acetoacetyl-CoA. HMG-CoA synthase — the regulatory enzyme of ketogenesis — adds a third acetyl unit to give HMG-CoA, and HMG-CoA lyase cleaves this to acetoacetate. Acetoacetate is then reduced to D-3-hydroxybutyrate by 3-hydroxybutyrate dehydrogenase, or decarboxylates spontaneously to acetone.
Metabolic properties
- They are water-soluble. Free fatty acids must travel bound to albumin; ketone bodies dissolve freely in plasma and require no carrier. This is the property from which all the others follow.
- They cross the blood-brain barrier, which free fatty acids cannot. In prolonged starvation the brain adapts to derive a large part of its energy from them — sparing body protein, since otherwise muscle amino acids would have to be sacrificed to gluconeogenesis to feed it.
- They are normal fuels of respiration. They are important substrates for heart muscle and renal cortex, which prefer them to glucose. Only the liver is excluded.
- The ratio between the two principal bodies reflects redox state. The acetoacetate/3-hydroxybutyrate equilibrium depends on the mitochondrial [NAD⁺]/[NADH] ratio; in fasting, β-oxidation raises NADH and drives the equilibrium towards 3-hydroxybutyrate, which is quantitatively predominant in blood and urine in ketosis.
- Acetone is not metabolised. It is volatile and is exhaled, producing the characteristic ketotic breath.
- They are relatively strong acids. In excess they consume buffer and produce ketoacidosis.
Why they are made — the oxaloacetate argument
Acetyl-CoA can only be oxidised in the citric acid cycle if oxaloacetate is available to condense with it — “fat burns in the flame of carbohydrate.” In starvation and in uncontrolled diabetes, oxaloacetate is drawn off into gluconeogenesis, the cycle cannot absorb the acetyl-CoA arriving from accelerated β-oxidation, and the surplus is condensed into ketone bodies. Ketogenesis is the overflow route for acetyl-CoA the citric acid cycle cannot accept.
Regulation
Ketogenesis is regulated at three successive stages: (1) lipolysis in adipose tissue, which sets the supply of free fatty acids — insulin is the principal antilipolytic hormone; (2) the activity of carnitine palmitoyltransferase-I, inhibited by malonyl-CoA, which decides whether fatty acids are oxidised or esterified; (3) the partition of acetyl-CoA between ketogenesis and the citric acid cycle.
Clinical significance
Ketosis arises when production outstrips peripheral oxidation. It is mild and physiological in starvation, after exercise and in pregnancy; it is severe in diabetes mellitus, where insulin lack removes the restraint on lipolysis and ketoacidosis follows. In ruminants, ketosis is a serious problem in lactating cattle and pregnant ewes.
Marking guide: naming all three bodies 1 · hepatic mitochondrial origin 1 · the missing CoA transferase and its consequence 1.5 · outline of the ketogenic pathway with HMG-CoA synthase named 2 · water-solubility and blood-brain barrier 1.5 · the oxaloacetate/citric-acid-cycle argument 1.5 · ketosis in starvation and diabetes 1.5. Both marking schemes stress the phrase 'the liver is the only organ that adds significant quantities to the blood' — use it verbatim.
2
Describe the pathway of fatty acid oxidation and calculate the ATP yield from palmitate.
8′
1 · Activation — in the cytosol
Acyl-CoA synthetase (thiokinase) converts the fatty acid to acyl-CoA, using ATP. ATP goes to AMP + PPi, and hydrolysis of the pyrophosphate ensures the reaction goes to completion — so the true cost is two high-energy phosphates.
2 · Transport — the carnitine shuttle
Long-chain acyl-CoA cannot cross the inner mitochondrial membrane. CPT-I on the outer membrane forms acylcarnitine; the translocase exchanges it inwards for free carnitine; CPT-II on the inner surface regenerates acyl-CoA in the matrix. CPT-I is the rate-limiting step and is inhibited by malonyl-CoA.
3 · The β-oxidation spiral
Four reactions per cycle, in the matrix — oxidation by acyl-CoA dehydrogenase (FAD) → hydration by enoyl-CoA hydratase → oxidation by 3-hydroxyacyl-CoA dehydrogenase (NAD⁺) → thiolytic cleavage by thiolase. Each cycle releases one acetyl-CoA and leaves an acyl-CoA two carbons shorter, which re-enters the spiral.
4 · The arithmetic for palmitate (C16)
| Source | Number | ATP each | ATP |
|---|---|---|---|
| FADH₂ (7 cycles) | 7 | 1.5 | 10.5 |
| NADH (7 cycles) | 7 | 2.5 | 17.5 |
| Acetyl-CoA in the citric acid cycle | 8 | 10 | 80 |
| Gross | 108 | ||
| Less activation | −2 | ||
| Net | 106 |
Note that C16 requires 7 cycles, not 8 — the last cycle produces two acetyl-CoA at once. State the P:O values you are using; with the older 3 and 2 the answer is 129 net, and this course's Lectures 10, 11 and 15 use the modern 2.5/1.5 figures.
5 · Variants
- Odd-chain acids end with propionyl-CoA, converted via methylmalonyl-CoA (biotin) to succinyl-CoA (vitamin B₁₂) — the only glucogenic part of a fatty acid.
- Unsaturated acids need an isomerase and a reductase, and yield about 1.5 ATP less per double bond.
- Peroxisomal β-oxidation shortens very long chain acids; its FADH₂ is oxidised directly to H₂O₂, so the energy is not captured as ATP.
- α-Oxidation handles branched-chain phytanic acid; its failure is Refsum disease.
Marking guide: activation with the two-phosphate cost 1 · carnitine shuttle, all three components 2 · the four reactions in correct order 2 · correct ATP arithmetic with the P:O values stated 2 · one variant pathway 1.