Comprehensive Lipid Lecture Notes
Overview of Lipid Super-Classes
- Lipids are unified by amphipathic nature – a hydrophobic hydrocarbon region + a polar head.
- Two structural “platforms” dominate:
- Glycerol-based (3-carbon tri-alcohol)
- Sphingosine-based (18-carbon amino-alcohol with an internal amide)
- Exam navigation rule:
- Identify the platform (glycerol vs sphingosine)
- Look for a phosphate – determines whether it is a phospholipid
- Look for carbohydrates – determines “glyco-” subclasses
Glycerophospholipids (a.k.a. Phosphoglycerides)
- Platform = glycerol (no carbon–carbon extensions off the 3-C backbone)
- Two esterified fatty-acyl chains at C1 & C2
- C3 bears a phosphate (± additional headgroup)
- Key headgroups to remember (Table 10-3):
- Phosphatidic acid (PA) – only PO_4^{2-} attached; minimal head
- Phosphatidylethanolamine (PE) – \mathrm{–CH2–CH2–NH_3^+}
- Phosphatidylcholine (PC) – choline: tetra-alkyl ammonium \mathrm{N^+(CH3)3} gives overall +1 formal charge
- Phosphatidylserine (PS) – the amino-acid serine supplies –CH2–CH(COO^-)–NH3^+
- Phosphatidylinositol (PI) – cyclic poly-alcohol (inositol) – resembles carbohydrate but ring contains only carbon atoms.
- Recognising trick: three isolated C’s + two ester bonds + phosphate = glycerophospholipid.
Glycoglycerolipids (plant / bacterial membranes)
- Same glycerol platform & two fatty acids
- Headgroup = one or several sugars (no phosphate) → NOT a phospholipid.
- Rare in animals; still examinable for recognition.
Sphingolipids / Ceramides
- Platform = sphingosine
- 18-carbon skeleton, long hydrocarbon tail is part of backbone.
- Two –OH, one –NH_2 (amide-forming site).
- Numbering note: textbook mislabels C-1; correct numbering starts at the head end.
- A single fatty acid is attached through an amide to the platform ⇒ core unit = ceramide.
- Diagnostic recognition:
- Presence of an internal amide on the platform (peptide-like bond)
- Long pre-existing hydrocarbon chain before any fatty-acyl addition
- If nitrogen appears within backbone → likely sphingolipid.
Sphingomyelin – the lone sphingophospholipid
- Ceramide + phosphate + choline head.
- Only sphingolipid that is also a phospholipid.
- Major component of neuronal myelin sheaths – critical during development.
Glycosphingolipids
- Ceramide + one or more sugars (no phosphate).
- Subclasses: cerebrosides, gangliosides, etc.
- Clinical/MCAT hook: ABO blood-group antigens are glycosphingolipid head variations (one extra sugar distinguishes A vs B; O = basic core).
Phospholipid vs Non-phospholipid Recap
- Glycerophospholipids + sphingomyelin = phospholipids (contain PO_4^{2-})
- Glycoglycerolipids & glycosphingolipids lack phosphate → not phospholipids.
Cholesterol & Steroid Lipids
- Synthesised from acetyl-CoA / fatty acids; 27 carbons.
- Structure: four fused rings + 8-carbon tail + single –OH → tiny polar head.
- Functions
- Membrane constituent (animals): modulates fluidity.
- Precursor of steroid hormones (testosterone, oestrogen, cortisol, etc.).
- Precursor of bile acids – emulsify dietary fat (soap analogy).
Cholesterol & Membrane Fluidity
- Key concept = van der Waals interactions → packing.
- Temperature effects (see textbook melting-curve graph):
- Low T°: bulky rigid rings disrupt packing ⇒ ↑ fluidity (prevents gelling)
- High T°: rings provide large contact area ⇒ restrain motion ⇒ ↓ fluidity (prevents membrane disintegration)
- Net effect: broadens phase transition – membranes stay functional over wider T° range.
Physical Analogies & Everyday Products
- Waxes = long-chain fatty acid esterified to a long-chain alcohol → extremely hydrophobic, solid at room T°; melt easily because only van der Waals hold molecules together (no covalent cross-links).
- Soap (saponified fatty acid salts)
- Generated by base (NaOH/KOH) hydrolysis of triglycerides.
- Amphipathic ions form micelles: hydrophobic tails sequester grease, polar carboxylate faces water → lifts fat off fabric/skin.
- Pop-culture link: “Fight Club” scene—human fat + lye → soap; NaOH burn neutralised by acid (vinegar).
- Glycerol + three fatty acids (no polar head other than ester carbonyls) – entirely hydrophobic.
- Stored in adipocytes (adipose tissue)
- Energy reservoir (more ATP per C than carbohydrate because carbons are more reduced)
- Cushioning of organs
- Thermal insulation (poor conductor of heat)
- Brown adipose tissue in infants & hibernators: uncoupled electron transport generates heat (non-shivering thermogenesis).
β-Oxidation – Using Fat for Energy
- Goal: convert fatty acids → \text{acetyl-CoA} for TCA cycle.
- Step 1 – Activation: \text{Fatty acid} + CoA + ATP \rightarrow \text{Fatty acyl-CoA} + AMP + PP_i
- Step 2 – Transport (Carnitine Shuttle):
- Fatty acyl group transferred to carnitine ⇒ fatty acyl-carnitine crosses inner mitochondrial membrane.
- Re-exchange for CoA inside matrix ⇒ fatty acyl-CoA ready for oxidation.
- Step 3 – Repeated 4-reaction cycle (dehydrogenation, hydration, dehydrogenation, thiolysis) shortens chain by 2 C per turn, releasing \text{acetyl-CoA} and generating FADH_2 & NADH.
- Analogy to glycolysis: different chemistry (redox of fully reduced hydrocarbons) but same endpoint – feed TCA & oxidative phosphorylation.
- \text{Glucose} \xrightarrow{glycolysis} \text{pyruvate} \xrightarrow{PDH} \text{acetyl-CoA} ↔ fatty-acid synthesis
- Fatty acids → TAG storage or membrane lipids.
- Fatty acids → cholesterol → steroid hormones & bile acids.
- TAGs → β-oxidation → acetyl-CoA → ATP + heat.
Key Exam / MCAT Tips
- Be able to:
- Recognise glycerol vs sphingosine backbones.
- Decide “phospho-” vs “glyco-” vs simple storage lipid.
- Name the five classic glycerophospholipid heads (PA, PE, PC, PS, PI) & choline structure \mathrm{N^+(CH3)3}.
- Remember: sphingomyelin = ONLY sphingo-phospholipid; everything else with sphingosine & sugars = glycosphingolipid.
- Explain cholesterol’s bidirectional effect on membrane fluidity.
- Outline the carnitine shuttle logic & why activation needs ATP.
- Practice: instructor will “throw a structure” – run platform → phosphate? → sugar? → name pathway.
