Step by Step
Gly
Glycerol backbone — the foundation
Glycerophospholipids are built on a glycerol backbone (3-carbon alcohol). Carbon 1 (sn-1) and carbon 2 (sn-2) are esterified to fatty acids. Carbon 3 (sn-3) is esterified to a phosphate group. The sn-2 position often carries an unsaturated fatty acid — creating the membrane kink.
Phos
Phosphate group and head group
The phosphate at sn-3 connects to a polar head group that determines the class: Phosphatidylcholine (PC) — most abundant, neutral. Phosphatidylethanolamine (PE) — inner leaflet, involved in fusion. Phosphatidylserine (PS) — inner leaflet, negative charge, apoptosis signal. Phosphatidylinositol (PI) — signaling precursor (PIP₂ → IP₃ + DAG).
Amp
Amphipathic structure — why membranes form
The combination of two hydrophobic fatty acid tails and one hydrophilic phosphate-head group makes glycerophospholipids amphipathic. This drives spontaneous bilayer formation in aqueous environments — the hydrophobic effect buries the tails, while the heads interact with water.
Asym
Membrane asymmetry
The two leaflets of the bilayer have different phospholipid compositions: Outer leaflet: PC, sphingomyelin. Inner leaflet: PE, PS, PI. PS on the outer leaflet is an 'eat me' signal for macrophages — a hallmark of apoptosis. Flippases maintain this asymmetry.
Applied Walkthrough
1
A glycerophospholipid in the outer leaflet of a red blood cell membrane: PC head group (choline), palmitate (16:0) at sn-1, oleate (18:1) at sn-2.
2
The unsaturated oleate at sn-2 creates a kink, preventing tight packing and maintaining membrane fluidity at body temperature.
3
During apoptosis, flippases are inactivated and scramblases expose PS to the outer leaflet — macrophages recognize PS and phagocytose the dying cell.
4
Phosphatidylinositol (PI) in the inner leaflet is phosphorylated to PIP₂. When cleaved by phospholipase C: IP₃ (triggers Ca²⁺ release) + DAG (activates protein kinase C) — two critical second messengers.
Exam Application
Exams test the glycerophospholipid structure (glycerol + 2 FA + phosphate + head group), the major head groups and their classes (PC, PE, PS, PI), membrane asymmetry, and PI's role in signaling (PIP₂ → IP₃ + DAG). Know that PS on the outer leaflet signals apoptosis — a classic exam question.
⚠ Common Trap
Students mix up the phospholipid head groups. The most important to memorize: PC = most abundant (outer leaflet). PS = inner leaflet, negative charge, flips out during apoptosis. PI = inner leaflet, signaling precursor. PE = inner leaflet, involved in membrane fusion. Also: the sn-2 position is almost always unsaturated in biological membranes.
✓ Quick Self-Check
1. What are the four components of a glycerophospholipid?
Glycerol backbone + 2 fatty acids (at sn-1 and sn-2) + phosphate group + polar head group (at sn-3).
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2. What determines the class of a glycerophospholipid?
The identity of the polar head group attached to the phosphate (choline = PC, ethanolamine = PE, serine = PS, inositol = PI).
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3. Which phospholipid is the precursor for the second messengers IP₃ and DAG?
Phosphatidylinositol bisphosphate (PIP₂) — cleaved by phospholipase C into IP₃ and DAG.
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4. What does phosphatidylserine (PS) on the outer leaflet signal?
Apoptosis — macrophages recognize externalized PS as an 'eat me' signal and phagocytose the dying cell.
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5. Why do glycerophospholipids spontaneously form bilayers?
They are amphipathic — hydrophobic tails avoid water (hydrophobic effect), hydrophilic heads interact with water — driving spontaneous bilayer assembly.
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