Chapter 34 — Quiz

Twenty-five questions on lipids, fatty acid biosynthesis, terpenes, and steroids. ∗ marks questions answered in the answer key.

Multiple choice

1.∗ Fatty acids are: (a) polar small molecules (b) long-chain carboxylic acids (typically C12-C22) (c) cyclic (d) only saturated

2.∗ Fatty acid biosynthesis adds 2 carbons per cycle from: (a) acetyl-CoA + malonyl-CoA (malonate provides the chain extension; CO₂ is released) (b) propanoate (c) acetyl-CoA only (d) glucose

3.∗ A phospholipid has: (a) only polar head (b) polar head + nonpolar tails (amphiphilic) (c) only nonpolar tails (d) only one fatty acid

4.∗ An isoprene unit has: (a) C₃ (3 carbons) (b) C₅ (5 carbons; 2-methyl-1,3-butadiene) (c) C₂ (d) C₁₀

5.∗ A monoterpene has: (a) C₁₀ (2 isoprenes) (b) C₅ (1 isoprene) (c) C₂₀ (4 isoprenes) (d) C₃₀

6.∗ Squalene is: (a) C₃₀ (the linear precursor to cholesterol) (b) C₁₀ (a monoterpene) (c) C₂₀ (a diterpene) (d) C₄₀ (a tetraterpene)

7.∗ Cholesterol is a: (a) triterpene-derived sterol (C₂₇, after losing 3 methyls from C₃₀ lanosterol) (b) primary alcohol (c) fatty acid (d) phospholipid

8.∗ β-oxidation of fatty acids yields: (a) acetyl-CoA + NADH + FADH₂ (b) ATP only (c) only acetyl-CoA (d) glucose

9.∗ A cell membrane is: (a) a lipid bilayer (~5 nm thick) (b) a single layer of lipids (c) a triglyceride layer (d) a protein layer

10.∗ A saturated fat has: (a) no C=C in the fatty acid chains (b) all C=C (c) one C=C (d) variable

11.∗ Why are most natural fatty acids cis-unsaturated? (a) cis is the kinetic product of the desaturase enzymes (b) cis is more stable than trans (c) trans isomers are toxic (d) all of the above

12.∗ The mevalonate pathway is the source of: (a) all terpenes (via IPP and DMAPP) (b) only fatty acids (c) only amino acids (d) carbohydrates

13.∗ HMG-CoA reductase is: (a) the rate-limiting step of cholesterol biosynthesis (the target of statins) (b) the rate-limiting step of fatty acid biosynthesis (c) the rate-limiting step of glycolysis (d) not an enzyme

14.∗ Statins lower cholesterol by: (a) inhibiting HMG-CoA reductase, blocking mevalonate formation, blocking cholesterol biosynthesis (b) blocking dietary absorption (c) increasing excretion (d) blocking acetyl-CoA

15.∗ The squalene cyclization to lanosterol: (a) is a single enzyme-catalyzed cationic polyene cyclization, setting 7 stereocenters in one step (b) requires multiple enzymes (c) occurs spontaneously without enzymes (d) is photochemical

16.∗ Vitamin D is made from: (a) 7-dehydrocholesterol + UV light + thermal isomerization (in the skin) (b) cholesterol + reduction (c) phenol + iodide (d) glucose

17.∗ Steroid hormones are derived from: (a) cholesterol (via cleavage of the side chain to give pregnenolone, then specific modifications) (b) amino acids (c) fatty acids (d) DNA

18.∗ ω-3 fatty acids (EPA, DHA) are essential because: (a) mammals lack the enzymes to introduce double bonds beyond Δ9 (b) they are toxic to make (c) they're acidic (d) all are correct

19.∗ Aspirin inhibits cyclooxygenase (COX), the enzyme that makes: (a) prostaglandins from arachidonic acid (C20:4 ω-6) (b) cholesterol from squalene (c) testosterone from cholesterol (d) glucose

20.∗ Triglycerides are: (a) the energy storage form of lipids (stored in adipose tissue) (b) cell membrane material (c) hormones (d) coenzymes

Short answer

21. Outline one cycle of fatty acid biosynthesis. Show acetyl-ACP + malonyl-ACP → β-keto-butyryl-ACP + CO₂ + ACP-SH; then the reduce-dehydrate-reduce sequence to give butyryl-ACP. Identify the 4 steps and the 4 enzymes (FAS or β-ketoacyl-ACP synthase, β-ketoacyl-ACP reductase, β-hydroxyacyl-ACP dehydratase, enoyl-ACP reductase).

22. Sketch the four levels of cholesterol's biosynthesis: (1) acetyl-CoA → mevalonate; (2) mevalonate → IPP; (3) IPP/DMAPP → squalene (via GPP, FPP); (4) squalene → lanosterol → cholesterol. Identify the rate-limiting step.

23. Compare and contrast: fatty acid biosynthesis vs β-oxidation. Use a 2-column table.

24. Sketch a phospholipid (e.g., phosphatidylcholine) and explain why it forms a bilayer in water.

25. Explain how statins lower LDL cholesterol. Connect to HMG-CoA reductase, mevalonate, and the upregulation of LDL receptors.

Answer key

  1. b — Long-chain carboxylic acids.
  2. a — Acetyl-CoA + malonyl-CoA, releasing CO₂.
  3. b — Phospholipid is amphiphilic.
  4. b — Isoprene = C₅.
  5. a — Monoterpene = C₁₀.
  6. a — Squalene = C₃₀.
  7. a — Cholesterol is C₂₇ (sterol).
  8. a — β-oxidation gives acetyl-CoA + NADH + FADH₂.
  9. a — Lipid bilayer.
  10. a — Saturated = no C=C.
  11. a — Cis is the kinetic product of desaturase.
  12. a — Mevalonate pathway → IPP → all terpenes.
  13. a — HMG-CoA reductase is the rate-limiting step.
  14. a — Statins inhibit HMG-CoA reductase.
  15. a — Polyene cyclization, 7 stereocenters in one step.
  16. a — Vitamin D from 7-dehydrocholesterol + UV.
  17. a — Steroid hormones from cholesterol.
  18. a — Mammals lack the enzymes for ω-3 desaturation.
  19. a — COX makes prostaglandins from arachidonic acid.
  20. a — Triglycerides are energy storage.

21. Cycle: - Step 1 (β-ketoacyl-ACP synthase): acetyl-ACP + malonyl-ACP → β-ketobutyryl-ACP + CO₂ + ACP-SH (the Claisen condensation; CO₂ release is the driving force). - Step 2 (β-ketoacyl-ACP reductase + NADPH): β-keto → β-hydroxy. - Step 3 (β-hydroxyacyl-ACP dehydratase): β-hydroxy → α,β-unsaturated (loss of water). - Step 4 (enoyl-ACP reductase + NADPH): α,β-unsaturated → saturated chain (now butyryl-ACP, 4 carbons). Net: 2 carbons added per cycle. 7 cycles for palmitate (16:0). 8 cycles for stearate (18:0).

22. Cholesterol biosynthesis: 1. Mevalonate phase: 2 acetyl-CoA → acetoacetyl-CoA (Claisen). + 1 acetyl-CoA → HMG-CoA. HMG-CoA + 2 NADPH → mevalonate (HMG-CoA reductase, the rate-limiting step). 2. Isoprene-formation phase: mevalonate + 3 ATP → IPP (3 phosphorylation + decarboxylation steps). IPP ↔ DMAPP. 3. Polyisoprene assembly: DMAPP + IPP → GPP (C₁₀); GPP + IPP → FPP (C₁₅); 2 FPP → squalene (C₃₀, head-to-head). 4. Cyclization to lanosterol: squalene → 2,3-oxidosqualene (via squalene monooxygenase) → lanosterol (cyclic, polyene cyclization). 5. Lanosterol → cholesterol: ~25 steps; remove 3 methyls; modify some C=C. Rate-limiting step: HMG-CoA reductase.

23. Comparison: | Feature | Biosynthesis | β-Oxidation | |---|---|---| | Location | Cytosol | Mitochondrion | | Direction | Build up (anabolic) | Break down (catabolic) | | Carrier | ACP (in fatty acid synthase) | CoA | | Reductant | NADPH | NAD⁺ → NADH; FAD → FADH₂ | | Driving force | CO₂ release (in Claisen) | Coenzyme reduction → ATP | | Per cycle | +2 carbons | -2 carbons (acetyl-CoA released) | | Rate-limiting step | Acetyl-CoA carboxylase | Carnitine palmitoyltransferase | | Substrate of cycle 1 | Acetyl-ACP + malonyl-ACP | Palmitoyl-CoA |

24. A phospholipid (e.g., phosphatidylcholine, POPC): - Polar head: phosphate + choline (positively charged at pH 7). - Two nonpolar fatty acid tails (e.g., palmitoyl + oleoyl). - Glycerol backbone.

In water, the polar head (which interacts favorably with water) faces outward; the nonpolar tails (which dislike water) face each other. Two layers of phospholipids form a bilayer: heads on the outside, tails facing each other in the middle. This is the lipid bilayer of cell membranes — ~5 nm thick. The driving force is the hydrophobic effect: nonpolar tails clustering releases water from their surfaces, which is entropically favorable.

25. Statins (atorvastatin, rosuvastatin, etc.) bind to HMG-CoA reductase's active site, mimicking the natural substrate's tetrahedral intermediate. This blocks the reductase's catalytic activity. Without HMG-CoA reductase, mevalonate isn't made; cholesterol biosynthesis is blocked. The liver responds by upregulating LDL receptors to take up LDL cholesterol from the blood (compensating for the reduced internal synthesis). Net result: blood LDL cholesterol drops by 30-60%. Long-term: less plaque formation in arteries → reduced cardiovascular events (heart attack, stroke).