Phospholipids

Core Concepts

The glycerol backbone and phosphate head

A glycerophospholipid (the major class) is glycerol with three substituents:

• Position 1: a fatty acid ester (saturated, e.g., palmitate 16:0)
• Position 2: a fatty acid ester (often unsaturated, e.g., oleate 18:1)
• Position 3: a phosphate diester to a head-group alcohol

Phosphatidic acid — glycerol + two fatty acids + one phosphate — is the parent compound. Esterifying the phosphate with an alcohol X–OH gives the full phospholipid. The most common head groups:

At physiological pH the phosphate carries a negative charge and choline/ethanolamine heads carry positive charge, so the head region is both charged and highly polar — very different from the neutral, greasy tails.

Why two tails mean a bilayer, not a micelle

Single-tailed amphiphiles (soaps, detergents) pack into micelles because a micelle's interior is small; the cone-shaped molecule fits perfectly. A double-tailed phospholipid is more like a cylinder — a large cross-section at the head and two tails that demand more interior volume. Packing cylinders into a sphere forces a hole in the middle, which costs energy. Instead, cylinders pack into a flat bilayer: heads on both faces, tails buried in the middle. This is a spontaneous, entropy-driven self-assembly, not a chemical reaction. The bilayer is about 4–5 nm thick, seals against ions and polar molecules, and lets small nonpolar molecules (O₂, CO₂) pass freely — the basis of the selectively permeable membrane.

Head-group identity controls function

The four head groups are not decoration. Phosphatidylcholine is the most abundant membrane lipid and the lecithin of commerce (an emulsifier in chocolate and salad dressings). Phosphatidylethanolamine favors curved regions. Phosphatidylserine, normally kept on the inner leaflet, flips to the outside when a cell dies — a signal for macrophages to engulf it. Phosphatidylinositol is the anchor for signaling cascades: cleavage of its head group releases second messengers (inositol trisphosphate, diacylglycerol). Head-group chemistry, in other words, is cell biology.

Membrane fluidity and the role of unsaturation

Membrane behavior depends on which fatty acids occupy positions 1 and 2. Cis-unsaturated tails kink and prevent tight packing, keeping the bilayer fluid; more unsaturation means a more fluid (lower-melting) membrane. Organisms adjust chain length and unsaturation to keep membranes functional at their body temperature — fish living in cold water carry more unsaturated fatty acids in their membranes than warm-water fish. Cholesterol (Topic 6) inserts into the bilayer and modulates fluidity in both directions: stiffening it when warm, preventing crystallization when cold.

Sphingophospholipids: a serine-based alternative

Sphingomyelin replaces glycerol with the amino alcohol sphingosine, CH₃(CH₂)₁₂CH=CHCH(OH)CH(NH₂)CH₂OH. One fatty acid is attached by an amide bond (forming a ceramide) and the terminal OH carries the phosphocholine head. Sphingomyelin is abundant in the myelin sheath that insulates nerve axons — a phospholipid built on a different backbone but the same head-tail logic.

How It Works / Step-by-Step Process

Reading a phospholipid structure:

1. Find the glycerol carbon skeleton (three carbons).
2. Identify the two ester linkages to fatty acids — note chain length and any C=C.
3. Find the phosphate on carbon 3: -OPO₃^-.
4. Identify the head-group alcohol esterified to the phosphate (choline = -CH₂CH₂N⁺(CH₃)₃).
5. Classify: PC, PE, PS, or PI, and state whether the tails are saturated or unsaturated.

Predicting aggregation in water: one tail and a cone shape → micelle; two tails and a cylinder shape → bilayer; three or more tails or bulky hydrophobic parts → hexagonal or inverted phases (beyond this course).

Common Confusions