Unit 2: Lipids and Amino acids

I. Orientation: Two Building Blocks of Life

Lipids and amino acids are the second and third great classes of biomolecules (after carbohydrates), one defined by solubility, the other by function. Lipids are grouped not by a shared structure but by a shared behaviour — insolubility in water and solubility in non-polar solvents (chloroform, ether). Amino acids are the monomers of proteins, defined by a fixed chemical skeleton bearing distinct side chains.

• Lipid defining trait: solubility, not structure — hydrophobic or amphipathic molecules that store energy (9 kcal/g vs 4 kcal/g for carbohydrate), form membranes, and act as signals.
• Amphipathy: many lipids carry both a hydrophobic tail and a polar head, driving self-assembly into bilayers and micelles.
• Amino acid skeleton: a central α-carbon bonded to an amino group (–NH₂), a carboxyl group (–COOH), a hydrogen, and a variable side chain (R).
• Zwitterion convention: at physiological pH the α-COOH is deprotonated (–COO⁻) and the α-NH₂ protonated (–NH₃⁺), so the free amino acid carries opposite charges simultaneously.
• The 20 standard set: proteins are built from 20 genetically encoded α-amino acids, all L-configuration except glycine (achiral).

II. Lipids — Storage, Structure and Signalling Molecules

A. Fatty acids and their properties

Fatty acids are long-chain monocarboxylic acids, the fundamental hydrocarbon unit of most lipids.

• General formula: CH₃–(CH₂)ₙ–COOH; a carboxyl head on a hydrocarbon tail, usually with an even number of carbons (C12–C24).
• Saturation:
  • Saturated: no C=C double bonds; straight chains that pack tightly — palmitic acid (16:0), stearic acid (18:0); solid at room temperature.
  • Unsaturated: one or more cis double bonds introduce a ~30° kink — oleic acid (18:1, Δ9), linoleic acid (18:2); liquid oils.
• Shorthand notation: written as carbons:double bonds, with double-bond position after Δ — 18:1 Δ9 is oleic acid.
• Melting point trend: rises with chain length, falls with unsaturation, because cis kinks disrupt packing and weaken van der Waals contacts.
• Essential fatty acids: linoleic (ω-6) and α-linolenic (ω-3) cannot be synthesised by humans and must come from diet.
• Amphipathic behaviour: the –COO⁻ head is hydrophilic, the tail hydrophobic, so fatty acids form micelles in water.

B. Classification of lipids

Lipids divide by whether they yield fatty acids on hydrolysis and by the presence of extra groups.

• Simple lipids: esters of fatty acids with alcohols — triacylglycerols (with glycerol) and waxes (with long-chain alcohols).
• Complex (compound) lipids: esters containing an additional group besides fatty acid and alcohol.
  • Phospholipids: contain phosphoric acid and often a nitrogen base.
  • Glycolipids: contain a carbohydrate residue.
• Derived lipids: hydrolysis products with lipid character — fatty acids, glycerol, steroids (cholesterol), fat-soluble vitamins (A, D, E, K).
• Functional grouping: storage lipids (fats), membrane lipids (phospho- and glycolipids, cholesterol), and lipids as signals or cofactors.

C. Triacylglycerol

Triacylglycerol (TAG) is the principal storage form of energy in animals and plants.

• Structure: glycerol esterified at all three hydroxyls by fatty acids.

        O
        ||
CH2–O–C–R1
        O
        ||
CH –O–C–R2
        O
        ||
CH2–O–C–R3

• Simple vs mixed: simple TAG has three identical fatty acids (tristearin); mixed TAG has different ones — the biological norm.
• Energy density: highly reduced and anhydrous, so it stores more than twice the energy per gram of glycogen.
• Hydrolysis: lipases cleave the ester bonds to free fatty acids and glycerol; alkaline hydrolysis (saponification) yields glycerol plus fatty-acid salts (soaps).
• Physical state: fats (solid, saturated-rich, animal) versus oils (liquid, unsaturated-rich, plant).

D. Waxes

Waxes are the simplest lipids — esters of long-chain fatty acids with long-chain monohydric alcohols.

• Structure: R–COO–R′, both R and R′ being C14–C36 chains, giving a fully hydrophobic, high-melting solid.
• Example: beeswax is largely myricyl palmitate (palmitic acid + C30 alcohol).
• Function: waterproofing and protection — plant cuticle, animal fur and skin, bird feathers.
• Inertness: no glycerol and no reactive polar head, so waxes resist hydrolysis and store energy poorly.

E. Phospholipids and glycolipids

Both are amphipathic membrane lipids; they differ in the polar group attached.

1. Phospholipids: built on a phosphate-linked head.
   • Glycerophospholipids: glycerol backbone, two fatty acids, and a phosphate esterified to a head group — choline (phosphatidylcholine/lecithin), ethanolamine, serine, or inositol.
   • Sphingophospholipids: sphingosine backbone instead of glycerol — sphingomyelin, abundant in nerve myelin.
   • Role: the primary bilayer-forming lipids of all cell membranes; the phosphate head faces water, the two tails face inward.
2. Glycolipids: built on a sugar head, no phosphate.
   • Cerebrosides: ceramide (sphingosine + fatty acid) bearing a single sugar (glucose or galactose).
   • Gangliosides: ceramide with a branched oligosaccharide including sialic acid (NANA); concentrated in neuronal membranes.
   • Role: cell-surface recognition, blood-group antigens, receptor sites — always on the outer membrane leaflet.

F. Cholesterol and its significance

Cholesterol is the principal steroid of animal tissue and the parent of all steroid derivatives.

• Structure: a rigid four-ring steroid nucleus (three six-membered + one five-membered ring), a hydroxyl at C3, and a branched C8 hydrocarbon tail — weakly amphipathic.
• Membrane role: its rigid ring system modulates fluidity, stiffening membranes above transition temperature and preventing tight packing below it.
• Biosynthetic precursor:
  • Bile acids/salts: for fat emulsification and absorption.
  • Steroid hormones: glucocorticoids, mineralocorticoids, and sex hormones (testosterone, estradiol).
  • Vitamin D: formed from 7-dehydrocholesterol in skin on UV exposure.
• Transport and significance: carried in blood as lipoproteins — LDL delivers cholesterol to tissues, HDL returns it to the liver; excess LDL deposits in arteries, driving atherosclerosis.

III. Amino acids — Monomers of Proteins

A. Structure and classification of amino acids

Amino acids share one skeleton but differ entirely in the side chain, which dictates classification.

• Common structure: the α-carbon bears –NH₃⁺, –COO⁻, –H and –R.
• Classification by R-group polarity:
  • Non-polar/hydrophobic: aliphatic or aromatic tails — glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan.
  • Polar uncharged: capable of hydrogen bonding — serine, threonine, cysteine, tyrosine, asparagine, glutamine.
  • Acidic (negatively charged): carboxylate side chains — aspartate, glutamate.
  • Basic (positively charged): amine or ring nitrogens — lysine, arginine, histidine.
• Nutritional class: essential (must be dietary) versus non-essential (synthesised in the body).

B. Stereochemistry of amino acids

Because the α-carbon carries four different groups, amino acids are chiral and optically active.

• Chiral centre: the α-carbon is asymmetric in all standard amino acids except glycine, whose R = H makes it achiral.
• D/L convention: configuration is assigned by comparison with glyceraldehyde, drawn as a Fischer projection with –COOH at top; the –NH₃⁺ on the left gives L, on the right gives D.
• Biological rule: proteins are built exclusively from L-α-amino acids.
• Isomer count: amino acids with two stereocentres (threonine, isoleucine) have four stereoisomers, including diastereomers (allo forms).
• Optical activity: each enantiomer rotates plane-polarised light equally but oppositely; L designation refers to configuration, not the sign of rotation.

C. Un-common amino acids

Beyond the 20 standard residues, cells contain modified and non-protein amino acids.

• Post-translationally modified residues: produced after protein synthesis.
  • 4-Hydroxyproline and 5-hydroxylysine: stabilise collagen triple helix.
  • γ-Carboxyglutamate: in prothrombin, binds Ca²⁺ for clotting.
  • Phosphoserine, phosphothreonine, phosphotyrosine: regulatory phosphorylation sites.
• Rare encoded residues: selenocysteine (the "21st") and pyrrolysine, inserted via special codon reassignment.
• Non-protein amino acids: metabolic intermediates never incorporated into proteins — ornithine and citrulline (urea cycle), GABA and homocysteine.

D. Titration curve of amino acids

The titration curve reveals the ionisable groups of an amino acid and their pKa values.

• Ionisable groups: at least two — α-COOH (pKa ≈ 2) and α-NH₃⁺ (pKa ≈ 9.5); acidic/basic side chains add a third.
• Sequence of proton loss: as pH rises, the strongest acid dissociates first — α-COOH before the side chain before α-NH₃⁺.
• Buffer regions: the curve shows plateaus centred on each pKa, where pH resists change; here [protonated] = [deprotonated].
• Henderson–Hasselbalch relation:

pH = pKa + log([A⁻]/[HA])

where HA is the protonated form, A⁻ the deprotonated form.

• Isoelectric point (pI): the pH of zero net charge, the average of the two pKa values flanking the zwitterion.

pI = (pKa1 + pKa2) / 2

• Worked example — glycine: with pKa1 = 2.34 and pKa2 = 9.60, pI = (2.34 + 9.60)/2 = 5.97; at this pH glycine exists almost entirely as the neutral zwitterion and does not migrate in an electric field.
• Charged side chains: for acidic or basic residues the pI uses the two pKa values bracketing the neutral species, shifting pI low for acidic (aspartate ≈ 2.8) and high for basic (lysine ≈ 9.7) amino acids.