Unit 18 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 four major lipoprotein classes, in order of INCREASING density, are ( ).
Answer: D
The organising principle: lipid is less dense than protein, so the more lipid a particle carries, the larger and less dense it is. Chylomicrons are ~99% lipid and float; HDL is about half protein and is the densest. Density and diameter therefore run in opposite directions — get that straight and the whole table follows.Harper's ch.25, p.254
2The four lipoprotein classes and their principal lipid cargo are correctly matched in ( ).
Answer: E
Two triacylglycerol-rich particles and two cholesterol-rich ones. The distinction between the first pair is the source: chylomicrons carry dietary (exogenous) fat from the intestine, VLDL carries endogenous fat made by the liver.Harper's ch.25, p.254
3The general structure of a plasma lipoprotein is ( ).
Answer: A
The design solves one problem: lipids are insoluble in plasma. Hide the hydrophobic cargo in the middle, turn the amphipathic molecules outward with their polar faces to the water, and the whole assembly becomes soluble. Free cholesterol is on the surface; cholesteryl ester is in the core — a distinction examiners like.Harper's ch.25, p.255
4Which apolipoprotein is the essential structural protein of LDL and the ligand for the LDL receptor?
Answer: B
Learn the five that matter. B-100 — made in liver, on VLDL/IDL/LDL, the LDL-receptor ligand. B-48 — made in intestine, on chylomicrons; it is 48% of the length of B-100, from the same gene by RNA editing, and lacks the receptor-binding domain. A-I — HDL, activates LCAT. C-II — activates lipoprotein lipase. E — remnant uptake.Harper's ch.25, pp.255, 258
5Lipoprotein lipase is ( ).
Answer: C
Note the elegance of the apo C-II requirement: the enzyme cannot act until it meets a particle carrying the right passport, so the lipoprotein itself licenses its own digestion. Insulin induces it in adipose tissue — in the fed state, fat is directed to storage. Option A describes hormone-sensitive lipase, option B LCAT, option D pancreatic lipase.Harper's ch.25, pp.256, 259
6LCAT (lecithin:cholesterol acyltransferase) ( ).
Answer: D
Why esterify? Free cholesterol sits on the surface; cholesteryl ester is nonpolar and sinks into the core. LCAT therefore keeps the surface concentration low so more cholesterol can flow in — the pump that drives reverse cholesterol transport. Option C is CETP; option E is HMG-CoA reductase.Harper's ch.25, p.261
7Reverse cholesterol transport is the process by which ( ).
Answer: E
This is why HDL is “good” cholesterol and LDL “bad”: they run in opposite directions. Cholesterol efflux from the tissue is mediated by the transporter ABCA1, and its deficiency causes Tangier disease — near-absent HDL, with cholesteryl ester deposited in tissues.Harper's ch.25, pp.261–262
8The LDL receptor-mediated uptake pathway of Brown and Goldstein proceeds by ( ).
Answer: A
The released cholesterol then does three regulatory things: it inhibits HMG-CoA reductase, suppresses synthesis of the LDL receptor, and activates ACAT to store the surplus as ester. The cell measures its own cholesterol and shuts off both making and importing.Harper's ch.25, pp.258–259 · Harper's ch.26
9Familial hypercholesterolemia is caused by ( ).
Answer: B
Without functional receptors, LDL cannot be cleared, plasma LDL rises, and cholesterol is deposited in arteries and tendons — premature atherosclerosis. Contrast familial lipoprotein lipase deficiency (type I), which causes hypertriacylglycerolemia with chylomicronemia, and abetalipoproteinemia, a failure to synthesise apo B.Harper's ch.25, pp.259, 264
10Chylomicron remnants are cleared by the liver by a receptor recognising ( ).
Answer: C
This is the point of the earlier detail — apo B-48 lacks the LDL-receptor-binding domain, so the remnant needs a different ticket, and apo E is that ticket. Note that apo E is a determinant of Alzheimer disease risk as well, an association worth knowing.Harper's ch.25, p.258
11During digestion, dietary triacylglycerol is emulsified by ( ) and hydrolysed by ( ).
Answer: D
Bile salts are amphipathic detergents that increase the surface area available to the enzyme — they do not hydrolyse anything. Colipase anchors pancreatic lipase to the emulsion in the presence of bile salts. The products, 2-monoacylglycerol and free fatty acids, are absorbed in mixed micelles.Harper's ch.25 · TMU Lecture 14
12After absorption, long-chain fatty acids in the enterocyte are ( ).
Answer: E
Contrast short- and medium-chain fatty acids, which are water-soluble enough to pass directly into the portal blood — the reason MCT oil is used clinically when lymphatic transport or micelle formation fails. Chylomicrons take the lymphatic route via the thoracic duct, bypassing the liver on first pass.Harper's ch.25 · TMU Lecture 14
13The metabolic fate of a chylomicron follows the order ( ).
Answer: A
The detail that HDL lends apo C-II and apo E and takes apo C-II back is exactly the sort of thing a 3-mark definition rewards. It also shows that HDL is not merely a scavenger but the plasma's apolipoprotein reservoir.Harper's ch.25, pp.257–258
14VLDL is converted in the circulation to LDL via ( ).
Answer: B
So LDL is what remains of a VLDL particle after its triacylglycerol has been stripped away — which is precisely why it ends up cholesterol-rich. IDL (VLDL remnant) is either taken up by the liver or converted onward. Roughly half of VLDL is recycled to LDL.Harper's ch.25, pp.259–260
15Hormone-sensitive lipase in adipose tissue is ( ).
Answer: C
The cascade is identical in shape to glycogenolysis (Unit 12): hormone → cAMP → protein kinase A → phosphorylation → activation. Two lipases, opposite jobs: lipoprotein lipase brings fat INTO the adipocyte and insulin induces it; hormone-sensitive lipase lets fat OUT and insulin inhibits it. Insulin is the principal antilipolytic hormone.Harper's ch.25, pp.262–263
16Free fatty acids are transported in plasma ( ).
Answer: D
This explains why free fatty acids cannot cross the blood-brain barrier — the albumin complex is far too large — and hence why the brain needs water-soluble ketone bodies in starvation (Unit 17). Free fatty acid turnover is very rapid, and the plasma concentration rises in starvation, diabetes and after epinephrine.Harper's ch.25, p.262
17Which statement about brown adipose tissue is correct?
Answer: E
This is Unit 9's uncoupling made physiological: a proton conductance pathway that short-circuits ATP synthase, so oxidation proceeds with heat as the product instead of ATP. The brown colour comes from the dense mitochondria and rich vascularisation. It is prominent in the newborn and in hibernating animals.Harper's ch.25, p.263 · Harper's ch.13
18Fatty liver of the non-alcoholic type may result from all of the following EXCEPT ( ).
Answer: A
More apo B-100 would help — it would export more triacylglycerol as VLDL. Harper's groups the causes into two categories: (1) too much fat arriving, as in starvation and diabetes; (2) a metabolic block in VLDL production, which may occur at any of the points in B, C, D or E. Choline deficiency is the classic example of the phospholipid failure, and its lipotropic action reverses it.Harper's ch.25, pp.264–265
19Ethanol causes fatty liver principally because ( ).
Answer: B
Alcohol dehydrogenase and aldehyde dehydrogenase both generate NADH, and the resulting redox shift has consequences across the liver's metabolism — it also impairs gluconeogenesis by favouring lactate over pyruvate, causing hypoglycemia. One altered ratio, several diseases.Harper's ch.25, p.265
20Cholesteryl ester transfer protein (CETP) ( ).
Answer: C
A useful discrimination question — four cholesterol-handling proteins, distinguished only by function. Option A is LCAT, option B is ABCA1. CETP provides an alternative route by which HDL-derived cholesterol returns to the liver: as LDL, rather than directly.Harper's ch.25, p.261
21Which lipoprotein has the HIGHEST protein content?
Answer: D
Roughly 50% protein in HDL, against 1–2% in chylomicrons. Since protein is denser than lipid, this is simply the same fact as “HDL is the densest” stated in another way. If you can reconstruct the density series from the protein content, you never need to memorise the table.Harper's ch.25, p.254
22Which fate is NOT available to acyl-CoA in the liver?
Answer: E
Fatty acids are not glucogenic, because pyruvate dehydrogenase is irreversible — the two carbons entering as acetyl-CoA cannot come back out as pyruvate. The sole exception is the propionyl-CoA from odd-chain acids (Unit 17). This is one of the most frequently examined negative facts in the whole subject.Harper's ch.19, p.193 · Harper's ch.22
23The 'lipotropic' action of choline refers to its ability to ( ).
Answer: A
Trace the mechanism back and it lands squarely on the lipoprotein structure question: the surface monolayer is made of phospholipid, so no phosphatidylcholine means no surface, no VLDL assembly, and triacylglycerol accumulates in the hepatocyte. Structure explains pathology.Harper's ch.25, p.265
24In the fed state, the fate of dietary fat is best described as ( ).
Answer: B
And the fasting picture is the exact inverse: insulin falls, hormone-sensitive lipase is activated, free fatty acids leave the adipocyte bound to albumin, muscle oxidises them, and the liver converts the surplus to ketone bodies. Two hormonal states, one set of enzymes read in opposite directions.Harper's ch.25, pp.259, 262–263
25Adipose tissue triacylglycerol synthesis requires glycerol-3-phosphate, which the adipocyte obtains ( ).
Answer: C
A consequence worth stating in an exam: the glycerol released by lipolysis cannot be reused by the adipocyte and passes into the blood, to be taken up by the liver, which does have glycerol kinase. It follows that fat storage depends on a supply of glucose — and hence on insulin — which is why lipolysis is unrestrained in uncontrolled diabetes.Harper's ch.24 · Harper's ch.25, p.262
1 Lipoproteins — 3′ — PROVEN 2020/21 Section I term+
Macromolecular complexes of lipid and protein that transport water-insoluble lipids in the blood plasma.
Structure: a nonpolar core of triacylglycerol and cholesteryl ester, surrounded by a surface monolayer of amphipathic phospholipid, free cholesterol and apolipoprotein, whose polar faces contact the aqueous plasma.
Four major classes, in order of increasing density and decreasing size:
• Chylomicrons — from the intestine, carry dietary triacylglycerol, apo B-48
• VLDL — from the liver, carry endogenous triacylglycerol, apo B-100
• LDL — the end product of VLDL catabolism, cholesterol-rich, delivers cholesterol to tissues
• HDL — reverse cholesterol transport, apo A-I, highest protein content (~50%)
Since protein is denser than lipid, the more lipid a particle carries the larger and less dense it is.Harper's ch.25, pp.254–255
Structure: a nonpolar core of triacylglycerol and cholesteryl ester, surrounded by a surface monolayer of amphipathic phospholipid, free cholesterol and apolipoprotein, whose polar faces contact the aqueous plasma.
Four major classes, in order of increasing density and decreasing size:
• Chylomicrons — from the intestine, carry dietary triacylglycerol, apo B-48
• VLDL — from the liver, carry endogenous triacylglycerol, apo B-100
• LDL — the end product of VLDL catabolism, cholesterol-rich, delivers cholesterol to tissues
• HDL — reverse cholesterol transport, apo A-I, highest protein content (~50%)
Since protein is denser than lipid, the more lipid a particle carries the larger and less dense it is.Harper's ch.25, pp.254–255
2 Apolipoproteins — 3′ — PROVEN 2019 Section I term+
The protein moieties of the plasma lipoproteins, situated in the amphipathic surface monolayer.
Three functions: (1) structural — they hold the particle together and confer solubility; (2) enzyme cofactors; (3) ligands for cell-surface receptors, determining where the particle is delivered.
The principal ones:
• apo B-100 — liver; VLDL, IDL, LDL; the ligand for the LDL receptor
• apo B-48 — intestine; chylomicrons; 48% of the length of B-100, from the same gene by RNA editing, and lacks the receptor-binding domain
• apo A-I — HDL; activates LCAT
• apo C-II — activates lipoprotein lipase
• apo E — mediates hepatic uptake of chylomicron remnants and IDLHarper's ch.25, pp.255–258
Three functions: (1) structural — they hold the particle together and confer solubility; (2) enzyme cofactors; (3) ligands for cell-surface receptors, determining where the particle is delivered.
The principal ones:
• apo B-100 — liver; VLDL, IDL, LDL; the ligand for the LDL receptor
• apo B-48 — intestine; chylomicrons; 48% of the length of B-100, from the same gene by RNA editing, and lacks the receptor-binding domain
• apo A-I — HDL; activates LCAT
• apo C-II — activates lipoprotein lipase
• apo E — mediates hepatic uptake of chylomicron remnants and IDLHarper's ch.25, pp.255–258
3 Lipoprotein lipase — 2′+
The enzyme on the capillary endothelium of extrahepatic tissues — chiefly adipose tissue, heart and skeletal muscle — which hydrolyses the triacylglycerol of chylomicrons and VLDL, releasing fatty acids for uptake by the tissue.
It requires apo C-II as an activator and phospholipid as a cofactor; insulin induces its synthesis in adipose tissue, directing fat to storage in the fed state.
Do not confuse it with hormone-sensitive lipase, which is intracellular, releases fatty acids out of the adipocyte, is activated by phosphorylation in response to epinephrine and glucagon, and is inhibited by insulin.
Deficiency causes familial hypertriacylglycerolemia (type I) with chylomicronemia.Harper's ch.25, pp.256, 262–263
It requires apo C-II as an activator and phospholipid as a cofactor; insulin induces its synthesis in adipose tissue, directing fat to storage in the fed state.
Do not confuse it with hormone-sensitive lipase, which is intracellular, releases fatty acids out of the adipocyte, is activated by phosphorylation in response to epinephrine and glucagon, and is inhibited by insulin.
Deficiency causes familial hypertriacylglycerolemia (type I) with chylomicronemia.Harper's ch.25, pp.256, 262–263
4 Reverse cholesterol transport — 2′+
The process by which HDL removes cholesterol from extrahepatic tissues and returns it to the liver, the only organ that can excrete cholesterol — in bile, as cholesterol or bile acids.
Nascent discoidal HDL from liver and intestine takes up free cholesterol from cell membranes via the transporter ABCA1. LCAT, activated by apo A-I, esterifies it using a fatty acid from phosphatidylcholine; the nonpolar ester moves into the core, keeping the surface concentration low so more cholesterol can flow in, and the disc becomes spherical HDL₃ then HDL₂.
The cholesteryl ester returns to the liver either directly, via scavenger receptor B1, or indirectly, transferred by CETP to VLDL and LDL.
This explains the inverse relation between HDL concentration and coronary risk. ABCA1 deficiency = Tangier disease.Harper's ch.25, pp.261–262
Nascent discoidal HDL from liver and intestine takes up free cholesterol from cell membranes via the transporter ABCA1. LCAT, activated by apo A-I, esterifies it using a fatty acid from phosphatidylcholine; the nonpolar ester moves into the core, keeping the surface concentration low so more cholesterol can flow in, and the disc becomes spherical HDL₃ then HDL₂.
The cholesteryl ester returns to the liver either directly, via scavenger receptor B1, or indirectly, transferred by CETP to VLDL and LDL.
This explains the inverse relation between HDL concentration and coronary risk. ABCA1 deficiency = Tangier disease.Harper's ch.25, pp.261–262
5 Fatty liver (hepatic steatosis) — 2′+
Accumulation of triacylglycerol in the liver, occurring when the rate at which triacylglycerol enters or is formed exceeds the rate at which it is exported as VLDL or oxidised.
Two categories of cause: (1) raised plasma free fatty acids from adipose tissue, as in starvation, diabetes mellitus and high-fat diets; (2) a metabolic block in VLDL production — a block in apolipoprotein synthesis, a failure to provide phospholipid (as in choline deficiency, whose reversal is the lipotropic action), or a failure of the secretory mechanism.
Ethanol causes fatty liver by raising the NADH/NAD⁺ ratio, which inhibits fatty acid oxidation and the citric acid cycle and favours esterification. Prolonged steatosis may progress to fibrosis and cirrhosis.Harper's ch.25, pp.264–265
Two categories of cause: (1) raised plasma free fatty acids from adipose tissue, as in starvation, diabetes mellitus and high-fat diets; (2) a metabolic block in VLDL production — a block in apolipoprotein synthesis, a failure to provide phospholipid (as in choline deficiency, whose reversal is the lipotropic action), or a failure of the secretory mechanism.
Ethanol causes fatty liver by raising the NADH/NAD⁺ ratio, which inhibits fatty acid oxidation and the citric acid cycle and favours esterification. Prolonged steatosis may progress to fibrosis and cirrhosis.Harper's ch.25, pp.264–265
1
Describe the classes of plasma lipoproteins, their apolipoproteins and their metabolic fates.
10′
The problem lipoproteins solve
Lipids are insoluble in water, yet must be moved between organs in an aqueous plasma. The solution is a particle with a nonpolar core of triacylglycerol and cholesteryl ester, wrapped in a surface monolayer of amphipathic phospholipid, free cholesterol and apolipoprotein. Because protein is denser than lipid, the more lipid a particle carries, the larger and the less dense it is — so density and diameter run in opposite directions across the four classes.
| Class | Origin | Main lipid | Main apo | Function |
|---|---|---|---|---|
| Chylomicrons | Intestine | Dietary TAG | B-48, C-II, E | Transport of dietary fat |
| VLDL | Liver | Endogenous TAG | B-100, C-II, E | Export of hepatic fat |
| LDL | From VLDL | Cholesterol | B-100 | Cholesterol to tissues |
| HDL | Liver, intestine | Phospholipid, cholesterol | A-I | Reverse cholesterol transport |
The apolipoproteins do three jobs
They are structural, they act as enzyme cofactors, and they are ligands for receptors. apo C-II activates lipoprotein lipase; apo A-I activates LCAT; apo B-100 binds the LDL receptor; apo E mediates hepatic remnant uptake. apo B-48 is 48% of the length of B-100, transcribed from the same gene and shortened by RNA editing, and it lacks the receptor-binding domain — which is exactly why chylomicron remnants must be cleared through apo E instead.
The exogenous pathway — dietary fat
Dietary triacylglycerol is emulsified by bile salts, hydrolysed by pancreatic lipase with colipase to 2-monoacylglycerol and free fatty acids, and absorbed in mixed micelles. In the enterocyte it is re-esterified by the monoacylglycerol pathway and packaged with apo B-48 into chylomicrons, which enter the lymph, not the portal blood. (Short- and medium-chain fatty acids go straight into the portal blood.)
In the circulation the chylomicron acquires apo C-II and apo E from HDL. Lipoprotein lipase on the capillary endothelium, activated by apo C-II, strips the triacylglycerol; the apo C-II is returned to HDL; and the remnant is taken up by the liver through apo E.
The endogenous pathway — hepatic fat
The liver secretes VLDL carrying apo B-100. Lipoprotein lipase removes its triacylglycerol progressively, forming IDL and then LDL — so LDL is simply the cholesterol-rich residue of a VLDL particle. LDL is taken up by receptor-mediated endocytosis: apo B-100 binds the receptor, the particle clusters in clathrin-coated pits, and lysosomal hydrolysis releases free cholesterol, which inhibits HMG-CoA reductase, suppresses LDL-receptor synthesis and activates ACAT.
Reverse transport — HDL
Nascent discoidal HDL takes up free cholesterol from cell membranes via ABCA1. LCAT, activated by apo A-I, esterifies it; the nonpolar ester sinks into the core, keeping the surface concentration low so more cholesterol can flow in, and the disc rounds into HDL₃ then HDL₂. The cholesteryl ester returns to the liver directly via scavenger receptor B1 or indirectly via CETP. Only the liver can excrete cholesterol, as cholesterol or bile acids in bile.
Clinical correlates
- Familial hypercholesterolemia — defective LDL receptor; raised LDL, premature atherosclerosis.
- Familial lipoprotein lipase deficiency (type I) — chylomicronemia and hypertriacylglycerolemia.
- Abetalipoproteinemia — failure to synthesise apo B; no chylomicrons or VLDL, fatty liver.
- Tangier disease — ABCA1 deficiency; near-absent HDL.
- LDL correlates positively and HDL inversely with coronary risk — because they carry cholesterol in opposite directions.
Marking guide: lipoprotein structure 1 · the four classes with density order 2 · apolipoprotein functions, at least three named correctly 2 · exogenous pathway including lipoprotein lipase and apo C-II 2 · VLDL→IDL→LDL and receptor uptake 1.5 · reverse cholesterol transport with LCAT 1 · one clinical correlate 0.5.
2
Discuss the causes of fatty liver.
5′
The balance that is disturbed
The hepatocyte is a busy transit point for fat, and triacylglycerol accumulates whenever the rate at which it arrives or is synthesised exceeds the rate at which it is exported as VLDL or oxidised. Every cause of fatty liver is a disturbance of one side of that balance, and Harper's groups them into two categories.
Category 1 — too much fat arriving
Raised plasma free fatty acids released from adipose tissue overwhelm the liver's export capacity. This occurs in starvation, diabetes mellitus and diets high in fat — all states of low insulin, in which hormone-sensitive lipase is unrestrained. It is accompanied by ketosis, since the same acetyl-CoA surplus drives ketogenesis.
Category 2 — a metabolic block in VLDL production
The liver cannot export what it cannot package. The block may lie at any point in the assembly line:
- A block in apolipoprotein synthesis — no apo B-100, no VLDL. The congenital form is abetalipoproteinemia; toxins such as carbon tetrachloride, chloroform, phosphorus, lead and arsenic and antibiotics such as puromycin produce the same effect acquired. Protein deficiency (kwashiorkor) acts here too.
- A failure to provide phospholipid for the surface monolayer — the classic case is choline deficiency, and the reversal of it is what is meant by the lipotropic action of choline. Essential fatty acid deficiency acts similarly.
- A failure of the secretory mechanism itself.
Ethanol — the important special case
Alcohol dehydrogenase and aldehyde dehydrogenase both generate NADH, so ethanol oxidation raises the NADH/NAD⁺ ratio. This inhibits fatty acid oxidation and the citric acid cycle, both of which require NAD⁺, and so diverts fatty acids into esterification. The same redox shift impairs gluconeogenesis by favouring lactate over pyruvate — hence alcoholic hypoglycemia. Chronically, the microsomal ethanol-oxidising system is induced, and prolonged steatosis may progress to fibrosis and cirrhosis.
Marking guide: statement of the export/input balance 1 · category 1 with two examples 1 · category 2 with at least two of the three blocks named 1.5 · choline and lipotropic action 0.5 · ethanol and the NADH mechanism 1.