Saturated fatty acids differ from unsaturated ones in:
A — Saturated fatty acids have NO C=C double bonds. Every carbon is “saturated” with hydrogen. This gives them a straight chain that packs tightly → solid at room temperature (e.g., butter, lard). Unsaturated fatty acids (B) have one or more C=C bonds. Option C is wrong; chain length is independent of saturation. Option D is wrong; saturated fats are common in animals.
McMurry & Ballantine 8e Ch 29 §29.1; Clayden Organic Chemistry 2e Ch 49
Question 2
Cis double bonds in unsaturated fatty acids:
B — Each cis double bond introduces a ~30° kink in the chain. This prevents close packing of adjacent chains → weaker van der Waals forces → lower melting point → oils (liquid at room temp). Trans double bonds (D) produce a straighter chain that packs more like saturated fats and arise during partial hydrogenation. Cis fats are actually thermodynamically less stable than trans (C is wrong).
McMurry 8e §29.1; Stryer Biochemistry 8e Ch 26
Question 3
Trans fats are harmful because:
C — Trans fats are technically unsaturated but their near-straight geometry behaves metabolically like saturated fats. They raise LDL (“bad”) cholesterol and lower HDL (“good”) cholesterol, increasing cardiovascular disease risk. They do NOT contain cholesterol (D is wrong). Formed by partial hydrogenation of vegetable oils (margarines, fried foods).
McMurry 8e §29.1; WHO guidelines on trans fatty acids
Question 4
Palmitic acid has the shorthand notation:
D — Palmitic acid = C16:0. Notation: C[chain length]:[double bonds]. A = stearic acid (C18:0, also saturated). B = oleic acid (C18:1, one double bond Δ9, monounsaturated). C = arachidonic acid (C20:4, four double bonds, ω-6 PUFA, precursor of prostaglandins).
McMurry 8e Table 29.1; Stryer Biochemistry 8e Ch 26
Question 5
An essential fatty acid must be obtained from diet because the body cannot synthesise it. Which of the following is NOT essential?
A — Palmitic acid is NOT essential. It is a saturated fatty acid synthesised de novo by the body from acetyl-CoA via fatty acid synthase. The two truly essential fatty acids are linoleic acid (ω-6) and α-linolenic acid (ω-3) — humans lack the desaturase enzymes to introduce double bonds beyond C9. Arachidonic acid (D) is conditionally essential (can be synthesised from linoleic acid if dietary supply is adequate).
McMurry 8e §29.1; Stryer 8e Ch 26.1
Question 6
A triglyceride (triacylglycerol) contains:
B — Triacylglycerol = glycerol backbone + 3 fatty acids joined by ester (C–O–CO–) bonds at the sn-1, sn-2, and sn-3 positions. A = wrong (that would be something like ATP). C = phospholipid (glycerophospholipid) structure. D = glycogen/starch. TAGs are the primary long-term energy storage form in adipose tissue; they yield ~9 kcal/g on oxidation.
McMurry 8e §29.2; Stryer 8e Ch 26.1
Question 7
The caloric (energy) value of dietary fat is approximately:
C — Fat yields ~9 kcal/g. Compare: carbohydrates and proteins yield ~4 kcal/g each; alcohol yields ~7 kcal/g. Fat’s high energy density reflects the highly reduced (electron-rich) C–H bonds in fatty acid chains — complete oxidation to CO₂ + H₂O releases more energy per gram.
McMurry 8e §29.2; Stryer 8e Ch 22
Question 8
Saponification of a fat with NaOH produces:
D — Saponification: fat + NaOH → glycerol + 3 fatty acid sodium salts (soaps). The three ester bonds are hydrolysed under alkaline conditions. The products are glycerol (water-soluble) and soap molecules (amphipathic: non-polar tail + polar carboxylate head). A = acid hydrolysis product (free fatty acids, not salts). This reaction is the industrial basis of soap manufacture.
McMurry 8e §29.3; reaction: (RCOO)₃C₃H₅ + 3NaOH → C₃H₅(OH)₃ + 3 RCOONa
Question 9
The enzyme that digests triglycerides in the small intestine is:
A — Pancreatic lipase cleaves fatty acids from the sn-1 and sn-3 positions of TAGs → 2-monoacylglycerol + 2 free fatty acids, absorbed by enterocytes. Bile salts emulsify fat droplets (increase surface area). B = starch digestion. C = protein digestion. D = lactose digestion. Lipase inhibitor orlistat blocks this enzyme as an anti-obesity drug.
Stryer 8e Ch 26.1; Rang & Dale Pharmacology 9e
Question 10
Phospholipids form bilayers because:
B — Amphipathic structure drives self-assembly into bilayers. The polar phosphate + head group faces water (hydrophilic exterior); the two fatty acid chains hide from water in the bilayer interior (hydrophobic core). This is the structural basis of all cell membranes. A = wrong; unsaturation introduces kinks that increase membrane fluidity. C = most phospholipids are zwitterionic (net neutral) or anionic.
McMurry 8e §29.4; Stryer 8e Ch 12.2
Question 11
Surfactant (DPPC — dipalmitoylphosphatidylcholine) deficiency in premature infants causes:
C — Neonatal RDS (Hyaline Membrane Disease). Surfactant is produced by type II pneumocytes from ~24 weeks gestation. It reduces alveolar surface tension, preventing collapse on expiration. Premature infants lack sufficient surfactant → alveoli collapse → respiratory distress. Treatment: exogenous surfactant instillation + antenatal maternal corticosteroids to accelerate fetal lung maturation.
Nelson Textbook of Paediatrics 21e Ch 122; McMurry 8e §29.4
Question 12
The steroid backbone (sterane nucleus) consists of:
D — The steroid nucleus: rings A, B, C are cyclohexane (6-membered); ring D is cyclopentane (5-membered). All four are fused. Total carbon skeleton = 17 carbons in the rings alone. Cholesterol has an additional 8-carbon side chain at C17 (total 27 carbons). Testosterone loses the side chain; estradiol is further aromatised at ring A.
McMurry 8e §29.5; Stryer 8e Ch 26.3
Question 13
Cholesterol is the precursor for:
A — Cholesterol is the precursor of: (1) all steroid hormones (glucocorticoids, mineralocorticoids, sex hormones); (2) bile acids (bile salts = emulsifiers for fat digestion); (3) vitamin D₃ (formed in skin by UV-B irradiation of 7-dehydrocholesterol). B = nucleotides come from ribose + nitrogen bases. C = amino acids from diet/protein. D = cholesterol cannot be converted back to glucose (the acetyl-CoA carbons are lost as CO₂).
Stryer 8e Ch 26.3; McMurry 8e §29.5
Question 14
LDL (“Low-Density Lipoprotein”) is considered “bad” cholesterol because:
B — LDL carries cholesterol from the liver to peripheral tissues. When LDL is oxidised or present in excess, it is taken up by macrophages in arterial walls → foam cells → fatty streaks → atheromatous plaques → coronary artery disease/MI/stroke. A = that is HDL’s role (reverse cholesterol transport). LDL is produced in the liver from VLDL.
Stryer 8e Ch 26.3; Kumar & Clark’s Clinical Medicine 10e Ch 34
Question 15
HDL (“High-Density Lipoprotein”) is “good” because:
C — HDL = reverse cholesterol transport. HDL picks up excess cholesterol from macrophages and peripheral cells (via ABCA1 transporter) → returns it to the liver → excreted in bile. High HDL is therefore protective against atherosclerosis. HDL is ~50% protein by weight (apoA-I is the major apoprotein); LDL is ~25% protein. A = the opposite (that is LDL). B = wrong; HDL has the highest protein:lipid ratio of all lipoproteins.
Stryer 8e Ch 26.3; Rang & Dale 9e Ch 23
Question 16
Statins lower cholesterol by inhibiting:
D — HMG-CoA reductase (3-hydroxy-3-methylglutaryl-CoA reductase) catalyses HMG-CoA → mevalonate, the rate-limiting step in cholesterol synthesis. Statins (e.g., atorvastatin, rosuvastatin) are competitive inhibitors. Blocking hepatic synthesis lowers intracellular cholesterol → liver upregulates LDL receptors → clears more LDL from blood. A = orlistat inhibits lipase. Statin discovery earned the 2008 Lasker Award.
Stryer 8e Ch 26.3; Rang & Dale 9e Ch 23
Question 17
Fat-soluble vitamins that are stored in adipose tissue and the liver are:
A — ADEK are the four fat-soluble vitamins. They are absorbed with dietary fat (require bile salts and chylomicrons for absorption) and stored in fat/liver. Because they accumulate, overdose (hypervitaminosis) is possible, especially for vitamins A and D. Water-soluble vitamins (B-complex, C) are excreted in urine and not stored to dangerous levels.
McMurry 8e §28.8; Stryer 8e Ch 19
Question 18
Vitamin D deficiency causes:
B — Vitamin D deficiency → reduced calcium & phosphate absorption from gut → defective bone mineralisation. In children (growing bones): rickets (bowed legs, soft skull, rachitic rosary on ribs). In adults: osteomalacia (bone pain, muscle weakness, stress fractures). A = Vitamin C deficiency. C = Vitamin A deficiency. D = Vitamin K deficiency. Active form = calcitriol (1,25-dihydroxycholecalciferol).
Stryer 8e §26.3; Kumar & Clark 10e Ch 18
Question 19
Vitamin K is required for:
C — Vitamin K is the cofactor for γ-glutamyl carboxylase. This enzyme γ-carboxylates specific Glu residues in clotting factors II (prothrombin), VII, IX, and X, as well as proteins C and S. γ-Carboxylation allows these proteins to bind Ca²⁺ and participate in the coagulation cascade. Deficiency → bleeding diathesis (prolonged PT/INR). Warfarin inhibits vitamin K epoxide reductase → anticoagulation. A = Vit A. B = Vit E. D = Vit D.
Stryer 8e §35.2; Kumar & Clark 10e Ch 35
Question 20
Waxes are esters of:
D — Waxes = long-chain fatty acid + long-chain alcohol (C₁⁶–C₃₀) joined by an ester bond. They are highly hydrophobic and solid at room temperature. Biological examples: carnauba wax (palm leaves), beeswax, sebum (skin surface waterproofing), spermaceti (whale). A = triacylglycerol (fat/oil). B = cholesterol esters (stored form of cholesterol). C = lysophospholipid or phospholipid precursor.
McMurry 8e §29.2; Stryer 8e Ch 26.1
D-1. Saturated fatty acid▼
A fatty acid with no carbon–carbon double bonds in the hydrocarbon chain. Every carbon is “saturated” with hydrogen. The straight, unbranched chain allows tight van der Waals packing → solid at room temperature (e.g., butter, lard). Key examples: palmitic acid (C16:0) and stearic acid (C18:0). Synthesised de novo in the liver from acetyl-CoA via fatty acid synthase; not dietary essentials. Contrast: unsaturated fatty acids carry one or more C=C double bonds (cis configuration in nature) that introduce kinks, reduce packing efficiency, and lower the melting point → oils.
McMurry 8e §29.1; Stryer 8e Ch 26.1
D-2. Triacylglycerol (triglyceride, TAG)▼
A lipid consisting of one glycerol backbone esterified with three fatty acids (at sn-1, sn-2, sn-3 positions via ester bonds). The major storage form of metabolic energy in adipose tissue; yields ~9 kcal/g on complete oxidation. TAGs are hydrophobic and stored in anhydrous fat droplets (efficient energy stores compared with hydrated glycogen). Digestion: pancreatic lipase cleaves sn-1 and sn-3 fatty acids → 2-monoacylglycerol + 2 free fatty acids. Hydrolysis by NaOH (saponification) → glycerol + fatty acid sodium salts (soap). Synthesis (in liver/adipose): from glycerol-3-phosphate + fatty acyl-CoA via GPAT, AGPAT, phosphatase, and DGAT.
McMurry 8e §29.2; Stryer 8e Ch 22.1
D-3. Saponification▼
Alkaline hydrolysis of an ester bond in a fat or oil by a strong base (NaOH or KOH). General equation: (RCOO)₃C₃H₅ + 3 NaOH → C₃H₅(OH)₃ + 3 RCOONa (soap). The reaction is irreversible under these conditions (contrast: acid hydrolysis is reversible). Products: glycerol (water-soluble) + fatty acid salts (soap; amphipathic molecules that form micelles to emulsify grease). Saponification number = mg KOH required to saponify 1 g of fat; higher value → shorter average chain length. The mechanism is nucleophilic acyl substitution: OH⁻ attacks the ester carbonyl → tetrahedral intermediate → alkoxide expelled → carboxylate salt.
McMurry 8e §29.3; Clayden 2e Ch 12
D-4. Phospholipid (glycerophospholipid)▼
A lipid containing a glycerol backbone, two fatty acid chains (sn-1 and sn-2), a phosphate group (sn-3), and a polar head group attached to phosphate. The fatty acid chains are hydrophobic; the phosphate + head group is hydrophilic → amphipathic molecule. In aqueous environments, phospholipids spontaneously self-assemble into bilayers (cell membranes) or micelles. Key phospholipids: phosphatidylcholine (lecithin), phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol. DPPC (dipalmitoylphosphatidylcholine) is the major component of pulmonary surfactant; deficiency in premature neonates causes respiratory distress syndrome (RDS). The sn-2 position commonly holds an unsaturated fatty acid, modulating membrane fluidity.
McMurry 8e §29.4; Stryer 8e Ch 12.2
D-5. Cholesterol▼
A 27-carbon sterol with the characteristic four-ring steroid backbone (three 6-membered rings A, B, C + one 5-membered ring D), an 8-carbon branched side chain at C17, an –OH group at C3, and a double bond at C5-C6. Biosynthesised in the liver from acetyl-CoA (via mevalonate and squalene; rate-limiting step: HMG-CoA reductase). Functions: (1) membrane fluidity regulator (intercalates between phospholipid fatty acid chains); (2) precursor of steroid hormones (cortisol, aldosterone, testosterone, oestrogen, progesterone); (3) precursor of bile acids (primary: cholic + chenodeoxycholic; enable fat digestion); (4) precursor of vitamin D (7-dehydrocholesterol → cholecalciferol by UV-B → 25-OH-D → calcitriol). Transported in blood as LDL (atherogenic) and HDL (protective).
McMurry 8e §29.5; Stryer 8e Ch 26.3
D-6. Statin (HMG-CoA reductase inhibitor)▼
A class of drugs that competitively inhibit HMG-CoA reductase (3-hydroxy-3-methylglutaryl-coenzyme A reductase), the enzyme catalysing HMG-CoA → mevalonate — the rate-limiting step in cholesterol biosynthesis in the liver. Mechanism of LDL lowering: reduced intracellular cholesterol → upregulation of hepatic LDL receptors → increased clearance of LDL from blood → lower plasma LDL. Examples: atorvastatin, rosuvastatin, simvastatin. Indications: primary and secondary prevention of cardiovascular disease, hypercholesterolaemia. Side effects: myopathy (myalgia → rhabdomyolysis, rare); elevated liver enzymes. Structural basis: statins mimic the HMG-CoA transition state at the active site of the enzyme.
Stryer 8e Ch 26.3; Rang & Dale 9e Ch 23
E1. Compare saturated and unsaturated fatty acids in structure, melting point, and health implications. Include cis vs trans configuration. (7 marks)7 marks
Structure:
Property
Saturated
Unsaturated (cis)
Trans fat
C=C bonds
None
One or more (cis)
One or more (trans)
Chain shape
Straight
Kinked (~30° per bond)
Near-straight
Packing
Tight
Loose
Semi-tight
Physical state (RT)
Solid (e.g., butter, lard)
Liquid (e.g., olive oil)
Semisolid (margarine)
Melting point
High
Low
Intermediate to high
Cis vs Trans: Natural unsaturated fats are cis (H atoms on same side of double bond) → kink prevents tight packing. Trans double bonds (H atoms on opposite sides) produce a straighter chain resembling saturated fats; formed by partial hydrogenation of vegetable oils (shortening, margarines, fried foods).
Health implications:
Saturated fats: raise LDL, increase cardiovascular risk; recommended <10% of energy intake.
Cis-unsaturated fats: monounsaturated (MUFA, e.g., oleic acid in olive oil) — neutral to protective; polyunsaturated (PUFA, ω-3 and ω-6) — anti-inflammatory, cardioprotective at moderate intake.
Trans fats: raise LDL and lower HDL simultaneously → doubly atherogenic; associated with MI, stroke; WHO calls for global elimination.
Essential fatty acids: linoleic (ω-6) and α-linolenic (ω-3) must come from diet; precursors of eicosanoids (prostaglandins, leukotrienes).
McMurry 8e §29.1; Stryer 8e Ch 26.1; WHO Trans Fat Elimination Plan 2018
E2. Describe the structure of a phospholipid and explain how it forms a bilayer. Why is surfactant (DPPC) critical for lung function, and what happens when it is absent in premature infants? (7 marks)7 marks
Phospholipid structure (glycerophospholipid):
Glycerol backbone with: fatty acid (sn-1, often saturated) + fatty acid (sn-2, often unsaturated) + phosphate + polar head group (sn-3).
Common head groups: choline (phosphatidylcholine/lecithin), ethanolamine, serine, inositol.
Result: amphipathic molecule — hydrophilic (polar) head + two hydrophobic (non-polar) tails.
Bilayer formation:
In aqueous solution, the hydrophobic effect drives phospholipids to orient with tails facing inward (away from water) and heads facing outward.
Two leaflets of phospholipids face each other tail-to-tail → lipid bilayer: hydrophilic exterior + hydrophobic core (~3 nm thick).
Bilayers are self-sealing, flexible, and the structural foundation of all cell membranes.
Membrane fluidity is modulated by: degree of unsaturation in tails (more kinks = more fluid) and cholesterol (buffers against temperature changes).
Surfactant (DPPC) and lung function:
Surfactant is produced by type II alveolar pneumocytes from ~24 weeks gestation; major component = DPPC (dipalmitoylphosphatidylcholine, fully saturated fatty acids for stability at body temperature).
At the air–liquid interface in alveoli, surfactant reduces surface tension during expiration (preventing alveolar collapse) and allows easy re-expansion during inspiration.
Physical principle: La Place’s law — the smaller the alveolus, the greater the tendency to collapse; surfactant counteracts this by reducing surface tension as alveolar radius decreases.
Alveoli collapse on each expiration → massive work of breathing → respiratory failure.
Fibrin + necrotic cells line the alveoli → hyaline membranes (histological hallmark).
Management: exogenous surfactant instillation (bovine/porcine extract) via endotracheal tube; antenatal corticosteroids (betamethasone) to accelerate fetal surfactant production.
McMurry 8e §29.4; Stryer 8e Ch 12.2; Nelson Paediatrics 21e Ch 122
E3. Explain the process of saponification. Write a general equation for the saponification of a triglyceride, name the products, and explain how soap micelles remove grease. (6 marks)6 marks
Definition: Saponification is the alkaline hydrolysis of ester bonds in fats/oils by a strong base (NaOH or KOH) to produce glycerol and fatty acid salts (soaps).
Mechanism (nucleophilic acyl substitution): OH⁻ is a strong nucleophile; it attacks the carbonyl carbon of each ester bond → tetrahedral intermediate → collapse expels the alkoxide (glycerol portion) → carboxylate is the stable product (irreversible due to resonance stabilisation of carboxylate).
How soap micelles remove grease:
In water, soap molecules aggregate into micelles: spherical structures with hydrophobic tails pointing inward and hydrophilic carboxylate heads pointing outward.
Grease/oil molecules are trapped inside the micelle core (like-dissolves-like: non-polar inside).
The outer hydrophilic shell keeps the grease-loaded micelle suspended in water → rinsed away.
Hard water (Ca²⁺, Mg²⁺) precipitates fatty acid salts as insoluble scum; hence synthetic detergents (sulfonate head groups, not affected by Ca²⁺) were developed.
Saponification number = mg KOH per gram of fat; higher value indicates shorter average chain length (more ester bonds per gram).
McMurry 8e §29.3; Clayden 2e Ch 12
E4. Describe the role of cholesterol in the body. Explain the functions of LDL and HDL, and the mechanism of action of statins. (8 marks)8 marks
Roles of cholesterol:
Membrane component: intercalates between phospholipids in cell membranes; modulates fluidity (prevents crystallisation at low temp, prevents excess fluidity at high temp) — “membrane fluidity buffer.”
Precursor of bile acids: cholic and chenodeoxycholic acids → conjugated with glycine/taurine → bile salts → emulsify dietary fats, enabling lipase action and fat-soluble vitamin absorption.
Precursor of vitamin D: 7-dehydrocholesterol → (UV-B in skin) → cholecalciferol (D₃) → (liver 25-hydroxylation) → 25(OH)D → (kidney 1α-hydroxylation) → calcitriol (1,25(OH)₂D, active form).
Biosynthesis: liver from acetyl-CoA via mevalonate pathway; rate-limiting step = HMG-CoA reductase.
LDL — Low-Density Lipoprotein:
Carries cholesterol esters and triglycerides from the liver to peripheral tissues.
When LDL is elevated (or oxidised), it is taken up by macrophages in arterial intima → foam cells → fatty streaks → atherosclerotic plaques → coronary artery disease, MI, stroke.
Performs reverse cholesterol transport: picks up excess free cholesterol from peripheral cells (ABCA1/ABCG1 transporters, macrophages) → carries it to the liver → excreted in bile or recycled.
Anti-atherogenic; high HDL is independently protective. HDL has the highest protein:lipid ratio (~50% protein, major apoprotein = apoA-I).
Stryer 8e Ch 26.3; Kumar & Clark 10e Ch 34; Rang & Dale 9e Ch 23
E5. Fat-soluble vitamins A, D, E, K: for each, state the active form, one key biochemical function, and the consequence of deficiency. (8 marks)8 marks
Night blindness (nyctalopia, earliest sign); progresses to xerophthalmia (corneal ulceration, Bitot’s spots); increased susceptibility to infections; keratomalacia (corneal softening, blindness).
D (Cholecalciferol)
Calcitriol [1,25(OH)₂D₃] — formed by sequential hydroxylation in liver (C25) then kidney (C1α)
Calcitriol binds VDR (nuclear receptor) → transcription of TRPV6 (intestinal Ca²⁺ channel) and calbindin → increases intestinal Ca²⁺ and phosphate absorption; promotes bone mineralisation.
Rickets in children (bowed legs, rachitic rosary, craniotabes); osteomalacia in adults (bone pain, proximal muscle weakness, pseudo-fractures); secondary hyperparathyroidism.
E (α-Tocopherol)
α-Tocopherol (most active form)
Lipid-soluble antioxidant: donates H to lipid peroxyl radicals (ROO•) within cell membranes → terminates lipid peroxidation chain reactions → protects polyunsaturated fatty acids in membranes from oxidative damage.
Rare in adults; haemolytic anaemia in premature infants (fragile red cell membranes); spinocerebellar ataxia and peripheral neuropathy (abetalipoproteinaemia).
K (Phylloquinone K₁; Menaquinone K₂)
Vitamin K hydroquinone (KH₂) — the active reduced cofactor
Cofactor for γ-glutamyl carboxylase: carboxylates specific Glu residues → γ-carboxyglutamate (Gla) in clotting factors II, VII, IX, X and anticoagulant proteins C and S → allows Ca²⁺-dependent phospholipid binding → coagulation cascade activation.
Bleeding diathesis: prolonged PT (factors II, VII ↓) and APTT (factors IX, X ↓). In newborns: Haemorrhagic Disease of the Newborn (HDN) → prophylactic IM vitamin K given at birth. Warfarin antagonises vitamin K → therapeutic anticoagulation.
Stryer 8e Ch 19; McMurry 8e §28.8; Kumar & Clark 10e Ch 16 & 35