Lipids and Biological Membranes

Fatty Acids

Fatty acids are monocarboxylic acids with long hydrocarbon chains (typically 4–36 carbons, with 12–24 being most common in human biochemistry). Systematic nomenclature: chain length followed by number of double bonds and their positions. Palmitic acid = hexadecanoic acid = 16:0 (16 carbons, 0 double bonds). Oleic acid = octadecenoic acid = 18:1(Δ9) = 18:1 cis-9 (18 carbons, 1 double bond at carbon 9, cis configuration). The carboxyl carbon is C1; the terminal methyl carbon is the omega (ω) carbon. Omega-nomenclature counts from the methyl end: linoleic acid = 18:2(Δ9,12) = 18:2 ω-6. Omega-3 fatty acids have the first double bond at carbon 3 from the methyl end (e.g., α-linolenic acid 18:3 ω-3). Omega-6 fatty acids have the first double bond at carbon 6 from the methyl end. Saturated fatty acids have no double bonds; their straight hydrocarbon chains pack tightly in crystalline arrays, giving them higher melting points (stearic acid 18:0 melts at 69.6°C; palmitic acid 16:0 at 63.1°C). Unsaturated fatty acids have one or more double bonds; natural double bonds are almost always cis, which introduces a rigid 30° kink that prevents tight packing and lowers the melting point (oleic acid 18:1 melts at 13.4°C). Trans fatty acids are produced industrially by partial hydrogenation of vegetable oils; the trans double bond resembles a saturated chain in its linear geometry, so trans fats pack more tightly than cis and have higher melting points. Trans fats raise LDL and lower HDL, increasing cardiovascular risk. Essential fatty acids cannot be synthesized by humans because we lack the Δ12 and Δ15 desaturases needed to introduce double bonds beyond C9: linoleic acid (18:2 ω-6) and α-linolenic acid (18:3 ω-3) are essential and must be obtained from the diet. From these, humans synthesize arachidonic acid (20:4 ω-6, the eicosanoid precursor), EPA, and DHA. Fatty acid melting points increase with chain length (more van der Waals interactions) and decrease with unsaturation (kinks prevent packing). Short-chain fatty acids (≤6 carbons) are water-soluble; medium- and long-chain fatty acids are increasingly hydrophobic and must be transported bound to albumin in the blood.

Triacylglycerols

Triacylglycerols (triglycerides, TAGs) are triesters of glycerol (a three-carbon trialcohol) with three fatty acids. They are neutral, nonpolar, hydrophobic molecules—the body's primary long-term energy storage form. TAGs are stored in adipocytes as large, anhydrous lipid droplets that occupy most of the cell volume. The complete oxidation of fatty acids yields approximately 9 kcal/g, compared to 4 kcal/g for carbohydrates and proteins. This superior caloric density has two reasons: (1) fatty acids are more reduced than carbohydrates (more C–H bonds per carbon = more electrons to donate to the electron transport chain), and (2) TAGs are stored anhydrously (glycogen is stored with ~2 g water per gram, diluting its effective energy density). Lipases hydrolyze TAGs to release free fatty acids and glycerol during fasting, exercise, or stress. Hormone-sensitive lipase (HSL) in adipocytes is activated by glucagon and epinephrine via cAMP-dependent protein kinase A (PKA) phosphorylation. The released free fatty acids travel in the blood bound to serum albumin and are taken up by tissues (muscle, heart, liver) for β-oxidation. Glycerol is phosphorylated to glycerol-3-phosphate, which can enter glycolysis or gluconeogenesis. The distinction between fats and oils is purely physical: fats are solid at room temperature (high saturated fatty acid content) while oils are liquid (high unsaturated content). Adipose tissue is not merely passive storage; it is an endocrine organ secreting leptin (satiety signal), adiponectin (insulin sensitizer), and inflammatory cytokines. Brown adipose tissue (BAT) expresses uncoupling protein 1 (UCP-1, thermogenin), which dissipates the proton gradient to generate heat instead of ATP—a process called non-shivering thermogenesis important in infants and hibernating animals. TAG synthesis (lipogenesis) occurs primarily in the liver and adipose tissue from glycerol-3-phosphate and fatty acyl-CoAs. The MCAT may ask you to calculate the net ATP yield from complete oxidation of a TAG given the component fatty acid chain lengths.

Phospholipids

Phospholipids are the fundamental structural lipids of biological membranes. They are amphipathic: they contain a hydrophilic (polar) head group and two hydrophobic fatty acid tails. This amphipathicity drives the spontaneous self-assembly of lipid bilayers in aqueous environments via the hydrophobic effect—water molecules are released from ordered cages around the hydrophobic tails, creating a net increase in entropy that is thermodynamically favorable. Glycerophospholipids (phosphoglycerides) are built on a glycerol-3-phosphate backbone: C1 and C2 of glycerol are esterified to two fatty acids (typically a saturated fatty acid at C1 and an unsaturated fatty acid at C2), and C3 is linked to a phosphate group, which is further esterified to an alcohol head group. The head-group alcohol defines the phospholipid class: phosphatidic acid (PA, –H as head group, the biosynthetic precursor), phosphatidylcholine (PC, lecithin, choline head group), phosphatidylethanolamine (PE, cephalin, ethanolamine head group), phosphatidylserine (PS, serine head group—net negative charge; its externalization to the outer leaflet is an apoptotic signal), phosphatidylinositol (PI, inositol head group—the phosphorylated derivatives PIP2 and PIP3 are key second messengers in signal transduction), phosphatidylglycerol (PG, glycerol head group), and cardiolipin (diphosphatidylglycerol, two PAs linked by a glycerol—found exclusively in the inner mitochondrial membrane, essential for crista structure and ETC supercomplex assembly). Plasmalogens have an ether-linked (vinyl ether, not ester) fatty acid at C1 instead of an ester-linked fatty acid; they are enriched in heart and brain tissue and their deficiency is associated with peroxisomal disorders. Platelet-activating factor (PAF) is a plasmalogen with an acetyl group at C2—it is a potent signaling molecule mediating inflammation and anaphylaxis at picomolar concentrations. The asymmetric distribution of phospholipids across the bilayer is actively maintained by flippases (ATP-dependent, move PS and PE to the inner leaflet), floppases (ATP-dependent, move PC and sphingomyelin to the outer leaflet), and scramblases (Ca2+-activated, bidirectional, collapse asymmetry during platelet activation and apoptosis). Phospholipases hydrolyze specific bonds in phospholipids: PLA1 cleaves the C1 ester, PLA2 cleaves the C2 ester (releases arachidonic acid—the rate-limiting step in eicosanoid synthesis), PLC cleaves the glycerol-phosphate bond (releases DAG and IP3), PLD cleaves the head-group-phosphate bond (releases phosphatidic acid and the free alcohol head group).

Sphingolipids

Sphingolipids are a class of membrane lipids built on sphingosine (an 18-carbon amino alcohol with a trans double bond between C4 and C5) rather than glycerol. The sphingosine backbone has three functional regions: a polar head (C1–C3 with amino and hydroxyl groups), an amide-linked fatty acid (forming ceramide), and a hydrocarbon tail. Ceramide is the simplest sphingolipid: sphingosine with a fatty acid attached via an amide bond to the C2 amino group. Ceramide serves as the biosynthetic precursor for all complex sphingolipids. Sphingomyelin is ceramide with a phosphocholine or phosphoethanolamine head group attached to the C1 hydroxyl. It is the only sphingolipid that contains phosphate and is a major component of the myelin sheath that insulates axons (together with galactocerebroside). Sphingomyelin is enriched in the outer leaflet of the plasma membrane. It is structurally similar to phosphatidylcholine (both have a phosphocholine head group) but uses ceramide as its hydrophobic anchor instead of diacylglycerol. Cerebrosides are ceramide with a single monosaccharide (glucose in glucocerebroside, galactose in galactocerebroside) attached at C1 via a glycosidic bond. Cerebrosides are neutral glycolipids—they have no net charge at physiological pH. Galactocerebroside is a major component of myelin. Globosides are ceramide with an oligosaccharide head group (2+ sugars): neutral glycolipids with no charge. Gangliosides are ceramide with an oligosaccharide head group containing one or more sialic acid residues (N-acetylneuraminic acid, NANA), which carry a negative charge at physiological pH. Gangliosides are concentrated in the outer leaflet of neuronal plasma membranes, where they contribute to the glycocalyx and participate in cell-cell recognition. The ganglioside GM1 is the receptor for cholera toxin; GM2 accumulation causes Tay-Sachs disease (deficiency of hexosaminidase A, which removes the terminal N-acetylgalactosamine from GM2). Sphingolipid storage diseases (sphingolipidoses) result from deficiencies in lysosomal enzymes that degrade sphingolipids: Gaucher disease (glucocerebrosidase deficiency → glucocerebroside accumulation), Niemann-Pick disease (sphingomyelinase deficiency → sphingomyelin accumulation), Fabry disease (α-galactosidase A deficiency → globotriaosylceramide accumulation), Tay-Sachs (hexosaminidase A deficiency → GM2 accumulation), Krabbe disease (galactocerebrosidase deficiency → galactocerebroside accumulation). All are autosomal recessive except Fabry (X-linked recessive).

Steroids

Steroids are lipids characterized by a core structure of four fused rings: three six-membered cyclohexane rings (A, B, C) and one five-membered cyclopentane ring (D)—the steroid nucleus (gonane). Cholesterol is the most abundant steroid in animals and the precursor for all other animal steroids: steroid hormones (glucocorticoids, mineralocorticoids, androgens, estrogens, progestins), bile acids, and vitamin D. Cholesterol has the four-ring steroid nucleus with a hydroxyl group at C3 (the only polar group—it orients toward the aqueous interface in membranes), two methyl groups at C18 and C19, an eight-carbon branched hydrocarbon tail at C17, and a double bond between C5 and C6. Cholesterol in membranes: intercalates between phospholipid fatty acid chains, with its hydroxyl group hydrogen-bonding to the ester carbonyl of phospholipids near the polar head-group region. This positioning enables cholesterol's dual effect on membrane fluidity: at temperatures above the phase-transition temperature (Tm), the rigid steroid ring system restrains fatty acyl chain motion, decreasing fluidity and reducing permeability; at temperatures below Tm, cholesterol disrupts the tight, ordered packing of saturated fatty acid chains, preventing the transition to the gel (solid-ordered) phase and maintaining fluidity. Cholesterol thus acts as a fluidity buffer—it broadens the phase transition and eliminates the sharp melting point of pure phospholipid bilayers. Lipid rafts are cholesterol- and sphingolipid-enriched microdomains in the plasma membrane that are more ordered and thicker than the surrounding membrane. They serve as platforms for signaling protein assembly and membrane trafficking. Cholesterol is transported in the blood as cholesterol esters (a fatty acid esterified to the C3 hydroxyl) packaged in lipoprotein particles. Cholesterol biosynthesis occurs primarily in the liver and begins with acetyl-CoA → HMG-CoA → mevalonate (the rate-limiting step catalyzed by HMG-CoA reductase, the target of statin drugs). Bile acids (cholic acid, chenodeoxycholic acid) are synthesized from cholesterol in the liver, conjugated to glycine or taurine, and secreted into bile to solubilize dietary fats for absorption. Steroid hormones: progesterone (C21, corpus luteum, maintains pregnancy), cortisol (C21, glucocorticoid, adrenal cortex—raises blood glucose, suppresses inflammation), aldosterone (C21, mineralocorticoid, adrenal cortex—increases Na+ reabsorption and K+ secretion in the kidney), testosterone (C19, androgen, testes—male sexual development), estradiol (C18, estrogen, ovaries—female sexual development). Vitamin D3 (cholecalciferol) is synthesized in the skin from 7-dehydrocholesterol upon UV exposure and is hydroxylated first in the liver (25-hydroxylation) then in the kidney (1α-hydroxylation) to the active form, calcitriol (1,25-dihydroxyvitamin D3), which regulates calcium and phosphate homeostasis.

Eicosanoids

Eicosanoids are a family of 20-carbon (Greek eikosi = twenty) signaling molecules derived from the polyunsaturated fatty acid arachidonic acid (20:4 ω-6). They are paracrine and autocrine agents—they act locally on nearby cells or on the same cell that produced them, have extremely short half-lives (seconds to minutes), and are not stored but synthesized on demand. The rate-limiting step is the release of arachidonic acid from membrane phospholipids by phospholipase A2 (PLA2), which is activated by Ca2+ and various stimuli (hormones, inflammatory signals, mechanical damage). Corticosteroids inhibit PLA2 via lipocortin (annexin-1), thereby blocking all eicosanoid synthesis—this is the molecular basis of their anti-inflammatory action. Once free, arachidonic acid is metabolized by two major pathways: (1) Cyclooxygenase (COX) pathway → prostanoids: prostaglandins (PGD2, PGE2, PGF2α), prostacyclin (PGI2), and thromboxanes (TXA2). COX has two isoforms: COX-1 (constitutively expressed in most tissues, produces prostaglandins for gastric mucosal protection, renal blood flow, and platelet aggregation) and COX-2 (inducible by inflammatory cytokines at sites of inflammation). NSAIDs (aspirin, ibuprofen, naproxen) inhibit both COX-1 and COX-2. Aspirin irreversibly acetylates COX (serine residue in the active site), while other NSAIDs are reversible competitive inhibitors. Selective COX-2 inhibitors (celecoxib, rofecoxib) spare the gastric COX-1-dependent protection but may increase cardiovascular risk by reducing PGI2 (vasodilator, anti-platelet) without affecting TXA2 (platelet aggregator, vasoconstrictor). (2) Lipoxygenase pathway → leukotrienes (LTB4, LTC4, LTD4, LTE4) and lipoxins. Leukotrienes are produced predominantly by leukocytes and are potent bronchoconstrictors (1000× more potent than histamine) and pro-inflammatory mediators—they are major players in asthma (targeted by leukotriene receptor antagonists like montelukast) and anaphylaxis (the slow-reacting substance of anaphylaxis, SRS-A, is a mixture of LTC4, LTD4, and LTE4). Prostaglandins: PGE2 mediates fever (acts on the hypothalamic thermoregulatory center), pain sensitization, and uterine contractions (used clinically for labor induction; PGE2 also keeps the ductus arteriosus patent in neonates). PGI2 (prostacyclin) is produced by endothelial cells, causes vasodilation, and inhibits platelet aggregation. TXA2 is produced by platelets, causes vasoconstriction, and promotes platelet aggregation. The balance between PGI2 and TXA2 regulates vascular tone and hemostasis. Low-dose aspirin selectively inhibits platelet TXA2 production (platelets cannot synthesize new COX because they lack nuclei) while sparing endothelial PGI2 production (endothelial cells can synthesize new COX), shifting the balance toward anti-thrombosis. PGF2α causes uterine contraction and is used for labor induction; it also lowers intraocular pressure (latanoprost, a PGF2α analog, is used for glaucoma).

Lipoproteins and Membrane Fluidity

Lipoproteins are macromolecular complexes that transport hydrophobic lipids (triacylglycerols and cholesterol esters) through the aqueous blood. Their structure: a hydrophobic core containing triacylglycerols and cholesterol esters, surrounded by a monolayer shell of phospholipids, free cholesterol, and apolipoproteins (apo). Apolipoproteins serve structural roles (apoB-100 in VLDL/LDL, apoB-48 in chylomicrons), act as ligands for receptors (apoB-100 and apoE for the LDL receptor, apoA-I for the HDL receptor), and activate enzymes (apoC-II activates lipoprotein lipase). The major lipoprotein classes, in order of increasing density (decreasing size and lipid content): Chylomicrons (largest, least dense, transport dietary triacylglycerols from the intestine to peripheral tissues; contain apoB-48). VLDL (very low-density lipoprotein, transports endogenously synthesized triacylglycerols from the liver to peripheral tissues; contains apoB-100, apoC-II, apoE). IDL (intermediate-density lipoprotein, a VLDL remnant; further metabolized to LDL). LDL (low-density lipoprotein, transports cholesterol to peripheral tissues; contains apoB-100; 'bad cholesterol'—elevated LDL is a major risk factor for atherosclerosis. LDL is taken up by cells via LDL receptor-mediated endocytosis). HDL (high-density lipoprotein, smallest, most dense, transports cholesterol from peripheral tissues back to the liver—reverse cholesterol transport; contains apoA-I; 'good cholesterol'). Lipoprotein lipase (LPL), located on capillary endothelial cells of muscle and adipose tissue, is activated by apoC-II and hydrolyzes triacylglycerols in chylomicrons and VLDL to release free fatty acids for tissue uptake. The LDL receptor recognizes apoB-100 and apoE; familial hypercholesterolemia results from defective or absent LDL receptors, causing elevated plasma LDL and premature atherosclerosis. Membrane fluidity is a critical property of biological membranes that affects permeability, protein diffusion, and membrane function. It is determined by three main factors: (1) Fatty acid saturation—unsaturated fatty acids with cis double bonds create kinks that prevent tight packing, increasing fluidity. Saturated fatty acids pack tightly, decreasing fluidity. Organisms regulate membrane fluidity by adjusting the ratio of saturated to unsaturated fatty acids (homeoviscous adaptation). (2) Cholesterol content—as described above, cholesterol buffers fluidity: it restricts motion at high temperatures (reducing fluidity) and prevents crystallization at low temperatures (maintaining fluidity). At very high concentrations, cholesterol can abolish the phase transition entirely. (3) Temperature—increased temperature increases fatty acyl chain motion, increasing fluidity. Decreased temperature reduces motion, decreasing fluidity and eventually causing the transition from the liquid-crystalline (fluid) phase to the gel (solid-ordered) phase at the phase-transition temperature (Tm). The fluid mosaic model (Singer-Nicolson, 1972): membranes are two-dimensional fluids in which both lipids and proteins are free to diffuse laterally within the plane of the bilayer. However, this diffusion is not entirely unrestricted—membrane proteins can be constrained by interactions with the cytoskeleton (e.g., spectrin in erythrocytes), by tight junctions (which separate apical and basolateral domains in epithelial cells), and by partitioning into lipid rafts. Transverse diffusion (flip-flop) of phospholipids from one leaflet to the other is extremely slow (hours to days) without enzyme catalysis because the polar head group must traverse the hydrophobic core. This is why flippases, floppases, and scramblases exist to catalyze transverse movement. The membrane also exhibits transmembrane asymmetry: phosphatidylserine and phosphatidylethanolamine are concentrated in the inner (cytoplasmic) leaflet, while phosphatidylcholine and sphingomyelin are concentrated in the outer leaflet. This asymmetry is functionally important—PS externalization marks cells for apoptotic clearance; PI(4,5)P2 in the inner leaflet is the substrate for PLC in signal transduction.

How it works

Lipid biology is governed by the hydrophobic effect—the thermodynamic drive to minimize water's contact with nonpolar surfaces. Fatty acids are the simplest lipids: a carboxylic acid head and a hydrocarbon tail. Saturate the tail (no double bonds) and it crystallizes at body temperature; add a cis double bond and the permanent kink prevents close packing, lowering the melting point. Esterify three fatty acids to glycerol and you have a triacylglycerol—an anhydrous, energy-dense fuel that yields 9 kcal/g. Replace one fatty acid with a phosphate-containing head group and the molecule becomes amphipathic: the basis of all biological membranes. The phospholipid bilayer is a two-dimensional fluid where individual lipids diffuse laterally but rarely flip-flop. The Singer-Nicolson fluid mosaic model describes this dynamic architecture, while cholesterol fine-tunes fluidity across temperature ranges. Sphingolipids, built on sphingosine, add structural diversity and are enriched in myelin and neuronal membranes. Eicosanoids are 20-carbon locals: they are made on demand from arachidonic acid, act within seconds, and are destroyed almost immediately—this is the biochemistry of inflammation, pain, and fever. Lipoproteins solve the solubility problem: how to move oily cargo through watery blood. Their density gradient—chylomicrons < VLDL < IDL < LDL < HDL—reflects their lipid-to-protein ratio, and each class has a distinct physiological role. The MCAT weaves these topics together: how does a cis double bond affect membrane fluidity? Why does aspirin reduce fever? What happens when LDL receptors are defective? Answering these questions requires connecting lipid structure to physiological function.

How it works

Lipid biology is governed by the hydrophobic effect—the thermodynamic drive to minimize water's contact with nonpolar surfaces. Fatty acids are the simplest lipids: a carboxylic acid head and a hydrocarbon tail. Saturate the tail (no double bonds) and it crystallizes at body temperature; add a cis double bond and the permanent kink prevents close packing, lowering the melting point. Esterify three fatty acids to glycerol and you have a triacylglycerol—an anhydrous, energy-dense fuel that yields 9 kcal/g. Replace one fatty acid with a phosphate-containing head group and the molecule becomes amphipathic: the basis of all biological membranes. The phospholipid bilayer is a two-dimensional fluid where individual lipids diffuse laterally but rarely flip-flop. The Singer-Nicolson fluid mosaic model describes this dynamic architecture, while cholesterol fine-tunes fluidity across temperature ranges. Sphingolipids, built on sphingosine, add structural diversity and are enriched in myelin and neuronal membranes. Eicosanoids are 20-carbon locals: they are made on demand from arachidonic acid, act within seconds, and are destroyed almost immediately—this is the biochemistry of inflammation, pain, and fever. Lipoproteins solve the solubility problem: how to move oily cargo through watery blood. Their density gradient—chylomicrons < VLDL < IDL < LDL < HDL—reflects their lipid-to-protein ratio, and each class has a distinct physiological role. The MCAT weaves these topics together: how does a cis double bond affect membrane fluidity? Why does aspirin reduce fever? What happens when LDL receptors are defective? Answering these questions requires connecting lipid structure to physiological function.

Comparisons

• B/B (Membrane structure): The fluid mosaic model, lipid bilayer asymmetry, and the effects of saturation/cholesterol on fluidity are foundational concepts that connect to cell signaling, transport, and organelle identity.
• B/B (Eicosanoids and inflammation): The COX pathway, the PGI2-TXA2 balance, and the mechanism of NSAIDs and corticosteroids link biochemistry to pharmacology and pathophysiology.
• B/B (Lipoproteins and cardiovascular disease): Chylomicron/VLDL/LDL/HDL metabolism, the LDL receptor pathway, and familial hypercholesterolemia are high-yield connections between biochemistry and pathology.
• B/B (Sphingolipidoses): Tay-Sachs, Gaucher, Niemann-Pick, Fabry, and Krabbe diseases test the connection between a specific enzyme deficiency and the accumulating sphingolipid substrate.
• C/P (Thermodynamics of self-assembly): Micelle, bilayer, and liposome formation driven by the hydrophobic effect (entropy-driven) connects lipid chemistry to thermodynamic principles.
• B/B (Steroid hormones): Cholesterol as the precursor for cortisol, aldosterone, testosterone, and estradiol—this links lipid structure to endocrine physiology and the HPA and HPG axes.
• C/P (Lipid solubility and drug design): The relationship between hydrophobicity, partition coefficients, and membrane permeability is tested in the context of drug absorption and blood-brain barrier crossing.

Common confusions

• Confusing cis and trans fatty acids. Cis double bonds create a kink (30°) and increase fluidity. Trans double bonds resemble saturated chains—straight geometry, tighter packing, higher melting point. Trans fats are industrially produced and atherogenic.
• Forgetting that natural unsaturated fatty acids are cis. The MCAT may show you a structure with a trans double bond and ask if it's naturally occurring—it is not (except in small amounts from bacterial fermentation in ruminants).
• Misidentifying which phospholipase cleaves which bond. PLA2 releases arachidonic acid from C2—this is the rate-limiting step for eicosanoid synthesis and is inhibited by corticosteroids. Know PLA1, PLA2, PLC, and PLD.
• Not knowing the difference between COX-1 and COX-2. COX-1 is constitutive (GI protection, platelet function). COX-2 is inducible (inflammation). Aspirin inhibits both irreversibly; celecoxib is COX-2 selective.
• Confusing the eicosanoid pathways. COX pathway produces prostaglandins, prostacyclin, and thromboxanes. Lipoxygenase pathway produces leukotrienes. NSAIDs block COX but not lipoxygenase.
• Reversing the LDL/HDL relationship. LDL delivers cholesterol to peripheral tissues (atherogenic—'bad'). HDL removes cholesterol from tissues and returns it to the liver (reverse cholesterol transport—'good'). This reversal is a classic trap.
• Thinking cholesterol only decreases membrane fluidity. At LOW temperatures, cholesterol PREVENTS tight packing and MAINTAINS fluidity. At HIGH temperatures, it restrains motion and DECREASES fluidity. It's a fluidity buffer, not a simple fluidity reducer.
• Confusing micelles, bilayers, and liposomes. Micelles form from single-tailed amphipathic molecules (detergents, fatty acid salts) and are spherical with hydrophobic tails inside. Bilayers form from two-tailed amphipathic molecules (phospholipids). Liposomes are spherical bilayer vesicles with an aqueous interior.
• Forgetting that triacylglycerols are the body's most efficient energy storage (9 kcal/g, stored anhydrously), not carbohydrates. A passage comparing TAG storage to glycogen storage is testing this energy-density distinction.
• Mixing up sphingolipid storage diseases. Tay-Sachs = GM2 ganglioside + hexosaminidase A. Gaucher = glucocerebroside + glucocerebrosidase. Niemann-Pick = sphingomyelin + sphingomyelinase. Fabry = globotriaosylceramide + α-galactosidase A. Krabbe = galactocerebroside + galactocerebrosidase.

Quick review

• Fatty acids = carboxylic acid + hydrocarbon tail. Saturated = no double bonds, straight, high MP. Unsaturated = cis double bonds, kinked, low MP. Natural = cis. Essential: linoleic (ω-6) and α-linolenic (ω-3).
• Triacylglycerols = glycerol + 3 fatty acids. Energy storage: 9 kcal/g, anhydrous. Stored in adipocytes. HSL (hormone-sensitive lipase) releases FAs during fasting via PKA phosphorylation.
• Phospholipids = glycerol-3-P + 2 fatty acids + polar head group. Amphipathic → bilayers. Classes: PC, PE, PS, PI, PG, cardiolipin. Asymmetric distribution maintained by flippase/floppase/scramblase.
• Phospholipases: PLA1 (C1 ester), PLA2 (C2 ester → releases arachidonic acid, inhibited by corticosteroids), PLC (glycerol-PO4 → DAG + IP3), PLD (head-group-PO4 → PA).
• Sphingolipids = sphingosine backbone + amide-linked FA + head group. Types: ceramide (simplest), sphingomyelin (phosphocholine, in myelin), cerebroside (1 sugar), globoside (2+ sugars), ganglioside (sialic acid).
• Sphingolipidoses: Tay-Sachs (GM2 + hexosaminidase A), Gaucher (glucocerebroside + glucocerebrosidase), Niemann-Pick (sphingomyelin + sphingomyelinase), Fabry (Gb3 + α-galactosidase A, X-linked).
• Steroids = 4-ring core. Cholesterol: membrane fluidity buffer (restrains at high T, prevents crystallization at low T). Precursor for steroid hormones, bile acids, vitamin D.
• Rate-limiting step in cholesterol synthesis: HMG-CoA → mevalonate (HMG-CoA reductase, target of statins).
• Eicosanoids = 20C signaling molecules from arachidonic acid. COX pathway → prostaglandins, prostacyclin, thromboxanes. Lipoxygenase pathway → leukotrienes. PLA2 release of AA is rate-limiting.
• COX-1 (constitutive, GI protection) vs COX-2 (inducible, inflammation). NSAIDs inhibit both; aspirin irreversibly acetylates COX. Low-dose aspirin favors anti-thrombotic PGI2/TXA2 balance.
• Lipoproteins (ascending density): Chylomicrons (dietary TAGs, apoB-48) → VLDL (hepatic TAGs, apoB-100) → IDL → LDL (cholesterol delivery, apoB-100, 'bad') → HDL (reverse cholesterol transport, apoA-I, 'good').
• LPL (lipoprotein lipase) activated by apoC-II; hydrolyzes TAGs in chylomicrons and VLDL. LDL receptor recognizes apoB-100 and apoE.
• Membrane fluidity increased by: unsaturation (cis double bonds, kinks), higher temperature. Decreased by: saturation (straight chains), cholesterol at high T. Cholesterol buffers fluidity at both extremes.
• Fluid mosaic model: 2D fluid, lipids and proteins diffuse laterally. Flip-flop is slow without enzymes. Membrane asymmetry: PS and PE inner leaflet, PC and sphingomyelin outer leaflet.