Lipids & Other Biomolecules – Detailed Lecture 5 Notes

Overview of Biomolecules

• Four fundamental biomolecule groups covered in General Biology II so far:
  • Carbohydrates → energy & structural cell‐wall material in bacteria/plants/algae.
  • Nucleic acids → encode & transmit genetic information.
  • Proteins → structural support & biological catalysts (enzymes).
  • Lipids → focus of Lecture 5; make up membranes, store energy, serve as signaling molecules.
• Lipids are not polymers; they are grouped together because they are predominantly hydrophobic hydrocarbons containing relatively little O.
• Core biological/physiological functions of lipids:
  1. Energy storage (highest energy per gram among biomolecules).
  2. Insulation (thermal) & mechanical protection of organs.
  3. Structural (major constituents of biological membranes).
  4. Precursors for steroids (hormones, vitamin D, cholesterol) & eicosanoids.

Definitions & Learning Objectives

• Differentiate fat (solid at room T°, usually saturated animal triglycerides) vs oil (liquid at room T°, usually unsaturated plant/ fish triglycerides).
• Lipid classes to recognize:
  • Fatty acids & triglycerides (neutral fats)
  • Waxes
  • Phospholipids
  • Sphingolipids
  • Glycolipids
  • Steroids
  • Eicosanoids
• Key conceptual abilities required by syllabus:
  • Write/recognize general fatty-acid formula; distinguish saturated vs unsaturated; explain cis vs trans; define essential FAs.
  • Show dehydration synthesis of triglyceride (formation of ester linkages, release of $3\,H_2O$) & its hydrolysis by lipases; explain neutrality, saponification, emulsification by soaps.
  • Describe hydrogenation & health impact of trans fats.
  • Compare triglycerides, phospholipids, sphingolipids, waxes; highlight amphipathic nature of emulsifiers.
  • Draw/describe steroid nucleus; list cholesterol roles, steroid hormones, bile acids, fat-soluble vitamins.
  • Explain amphipathicity of bile acids & phospholipids.
  • Differentiate hormone (intra-organismic signal) vs pheromone (inter-organismic signal).
  • Define eicosanoid, prostaglandin, leukotriene, thromboxane; relate to action of aspirin & acetaminophen.

Fatty Acids

• General structural formula (saturated): $\mathrm{CH<em>3(CH</em>2)_nCOOH}\,.$
  • At physiological pH, the –COOH deprotonates → $\mathrm{COO^-}$ (anion).
  • Amphipathic: polar carboxylate head (hydrophilic) + long apolar hydrocarbon tail (hydrophobic).
• Length: most common 16-22 C (can vary 2-26+).
• Saturated FAs
  • All C–C single bonds; "saturated with H".
  • Pack tightly → more van-der-Waals contacts → solid at room T° (e.g., butter).
• Unsaturated FAs
  • ≥1 C=C double bond, usually cis → kinks, less packing → liquid at room T° (olive oil).
  • Each C=C reduces van-der-Waals interactions & melting point.
• Trans fats
  • Formed industrially during hydrogenation (addition of $H_2$ + catalyst to saturate oils for shelf stability).
  • Some C=C re-form in trans geometry → linear tail, packs like saturated fat but raises LDL, lowers HDL, increases atherosclerosis risk.
• Essential fatty acids (EFA)
  • Cannot be synthesized by humans; must be obtained from diet.
  • Two parents:
  • Linoleic acid (LA) $18:2\,n{-}6$ (omega-6)
  • \alpha-Linolenic acid (ALA) $18:3\,n{-}3$ (omega-3)
  • Desaturase & elongase enzymes convert parents → long-chain PUFAs (e.g., AA, EPA, DHA); compete for same enzymes → dietary $\omega<em>6:\omega</em>3$ ratio important (Western ≈15:1; recommended much lower).
  • Biological roles: membrane fluidity, vision & CNS (DHA dominant PUFA in retina/neuron), precursors for eicosanoids.

Triglycerides (Triacylglycerols, TAG)

• Constructed from glycerol (a 3-carbon triol) + 1-3 fatty acids.
  • Monoglyceride (1 FA), diglyceride (2 FAs), triglyceride (3).
• Dehydration synthesis / esterification:
  $\text{Glycerol} + 3\,\text{Fatty Acids} \xrightarrow[\text{Esterase\, reversible}]{\text{Dehydration}} \text{Triglyceride} + 3\,H_2O$
• Ester bond: $\mathrm{R{-}COO{-}CH_2}$ linkage between FA carboxylate & glycerol OH.
• Neutral fats
  • Non-ionic (esterified acid loses charge) → "neutral".
• Functions
  1. Energy reserve (double energy density of polysaccharides; fat 9 kcal/g vs carbs 4 kcal/g; also stored anhydrously unlike glycogen that binds $2\,g\,H_2O$ per g).
  2. Insulation (subcutaneous adipose).
  3. Cushioning of organs.
• Hydrolysis
  • Enzyme: lipases (pancreatic, hormone-sensitive, etc.) cleave ester bonds → glycerol + free FAs.
• Saponification (soap making)
  • Base-catalyzed hydrolysis with strong alkali (NaOH/KOH):
    $\text{TAG} + 3\,OH^- \rightarrow \text{Glycerol} + 3\,\text{Fatty Acid Salts (soap)}$
  • Soap = sodium/potassium carboxylate; amphipathic, forms micelles → emulsifies grease.
• Physiological emulsification
  • In intestine, large TAG droplets broken by bile salts into micelles ↑surface area for pancreatic lipase.
  • Products (2-monoacylglycerol + free FAs) diffuse into enterocytes → re-esterified → chylomicrons → lymphatics → blood.
• Health link
  • Diets rich in saturated or trans FAs ↑ risk of atherosclerosis (plaque, vessel stiffening, MI).

Phospholipids

• Backbone: glycerol + 2 FAs (positions 1 & 2) + phosphate esterified to a polar head group at position 3.
  • Common head groups:
  • Choline (phosphatidylcholine – most abundant)
  • Ethanolamine (PE)
  • Serine (PS)
  • Inositol (PI)
• Amphipathic:
  • Hydrophobic tails = FA chains.
  • Hydrophilic head = phosphate + charged group + glycerol carbonyls.
• In water → self-assemble:
  • Bilayers (basis of plasma & organelle membranes)
  • Micelles (small single-layer spheres)
  • Liposomes (bilayer vesicles; drug delivery models).
• Membrane fluidity governed by FA length & unsaturation (#double bonds) and cholesterol; organisms adjust composition seasonally.

Sphingolipids

• Built on sphingosine (18-C amino-diol) instead of glycerol.
• Core = ceramide (sphingosine + FA amide-linked to –NH₂).
• Variants:
  • Sphingomyelin: phosphocholine head; abundant in myelin sheath → electrical insulation; demyelination → multiple sclerosis.
  • Glycosphingolipids: saccharide head groups.
  • Gangliosides (complex oligosaccharides + sialic acid); cell-cell recognition, nerve tissues; GM₂ accumulation (lack of hexosaminidase A) → Tay-Sachs disease.

Glycoconjugates (lipid- or protein-linked carbohydrates)

• Glycoproteins: proteins + few oligosaccharides; extracellular side of membranes; cell‐cell recognition (e.g., immune receptors).
• Proteoglycans: core proteins + very large glycosaminoglycan (GAG) chains (≈95 % carbohydrate); major ECM component; store water → compressive resistance (cartilage).
• Glycolipids: carbohydrate attached to lipid (often ceramide or glycerolipid); amphipathic like phospholipids.
  • ABO blood group antigens are glycolipids on erythrocyte membrane; type‐O core present in all; mismatched antigen triggers antibodies.

Waxes

• Long-chain fatty acid esterified to long-chain fatty alcohol (not glycerol) → two long hydrocarbon tails.
• Extremely hydrophobic; water-repellent coatings on leaves, feathers, exoskeleton.
• Examples:
  • Cetyl palmitate – principal component of spermaceti (sperm-whale head oil).
  • Triacontanyl palmitate – beeswax.

Steroids

• Sterol nucleus: four fused rings (3 hexagons + 1 pentagon) ≈ $\mathrm{C_{17}}$ core; side-chains & substituents confer identity.
• Cholesterol
  • Inserted between phospholipid tails; modulates membrane fluidity:
  • Above $37\,^\circ!\mathrm{C}$: restrains movement (↓fluidity).
  • Below transition T°: prevents packing (↑fluidity).
  • Precursor for all other steroids.
• Steroid hormones (lipophilic → cross membranes, bind nuclear receptors, regulate gene expression):
  • Sex hormones: testosterone, estradiol.
  • Adrenal cortex: cortisol (stress/glucose), aldosterone (Na⁺ balance).
• Bile acids (e.g., cholic acid): amphipathic detergents secreted into intestine to emulsify dietary lipids (physiological equivalent of soap).
• Vitamin D family: UV-photolysis of 7-dehydrocholesterol → cholecalciferol (D₃) → liver/kidney hydroxylations → $1,25\,(\mathrm{OH})<em>{2}!\text{D}</em>3$; hormone regulating Ca²⁺/phosphate homeostasis.
• Terminology:
  • Hormone = endogenous signaling molecule within one organism.
  • Pheromone = exogenous signaling molecule between organisms of same species.

Eicosanoids

• Derived from 20-C PUFAs (mainly arachidonic acid, AA; 20:4\,n-6).
• Liberation: phospholipase A₂ cleaves AA from membrane phospholipids.
• Branch pathways:
  • Cyclooxygenase (COX) → cyclic endoperoxide → prostaglandins (pain, fever, inflammation, gastric protection) & thromboxanes (platelet aggregation, vasoconstriction) .
  • Lipoxygenase → leukotrienes (bronchoconstriction, allergy/asthma).
• Pharmacology:
  • NSAIDs (Aspirin, ibuprofen) irreversibly/competitively inhibit COX-1 & COX-2 → ↓prostaglandins & thromboxanes; side-effects (bleeding, ulcers, renal) due to COX-1 inhibition.
  • COX-2 selective inhibitors (celecoxib) spare gastric/platelet functions.
  • Corticosteroids up-regulate lipocortin → inhibit phospholipase A₂ → block both prostaglandin & leukotriene synthesis.
  • Acetaminophen (Tylenol) antipyretic/analgesic; central mechanism; minimal anti-inflammatory activity (mode still debated).

Hormones (General Perspective)

• Chemical messengers secreted by one cell/tissue, travel (blood or local diffusion) to target cells with specific receptors → trigger signal-transduction cascades.
• Three chemical categories:
  1. Peptide/Protein hormones (e.g., insulin, growth hormone).
  2. Lipid derivatives (steroids, eicosanoids).
  3. Monoamines (amino-acid derived, e.g., dopamine, epinephrine).

Vitamins (Brief Survey)

• Defined as organic compounds required in trace amounts that cannot be synthesized by the organism; specificity means a chemical can be vitamin for one species but not another.
• Fat-soluble (A, D, E, K)
  • A (retinol) – vision (rhodopsin), immune; deficiency → night blindness.
  • D (cholecalciferol) – calcium metabolism (see steroids).
• Water-soluble B-complex (B₁, B₂, B₃, B₅, B₆, B₇, B₉, B₁₂) – metabolic coenzymes.
  • B₁₂ deficiency → neurological damage.
• Vitamin C (ascorbic acid) – antioxidant, collagen synthesis; deficiency → scurvy.

Practical & Ethical Implications

• Industrial hydrogenation prolongs shelf-life but produces harmful trans fats; public-health regulations now limit trans-fat content.
• Over-consumption of saturated/trans fats contributes to cardiovascular disease; dietary guidelines emphasize PUFA/MUFA and balanced $\omega<em>6:\omega</em>3$ ratio.
• NSAID overuse risks GI bleeding & renal impairment; COX-2 inhibitors mitigate some risks but raise concerns about thrombosis.
• Genetic lipid disorders (e.g., Tay-Sachs ganglioside accumulation) highlight necessity of neonatal screening & ethical counseling.

Numerical / Statistical Highlights

• Energy comparison: $1\,\text{g fat} \approx 9\,\text{kcal},\quad 1\,\text{g carbohydrate/protein} \approx 4\,\text{kcal}.$
• Glycogen stores water at roughly $2\,\text{g H}_2\text{O}$ per gram; TAG stores virtually none.
• Western diet average $\omega<em>6:\omega</em>3 \approx 15:1$; suggested optimum ≤$4:1$.

Concept Map / Interconnections

• Fatty acids are building blocks for triglycerides (energy) & phospholipids/sphingolipids (membranes) & cholesteryl esters.
• Membrane phospholipids not only form bilayers but serve as reservoirs of arachidonic acid for eicosanoid biosynthesis.
• Cholesterol both stabilizes membranes and acts as precursor to steroid hormones, bile acids, vitamin D.
• Bile acids, phospholipids, and soaps share amphipathic structure → emulsification principle repeated in digestion, metabolism, and industry.