Phospholipids and Cholesterol

Spec mapping — OCR H420 Module 2.1.2 — Biological molecules. This lesson develops the structure of phospholipids (glycerol + 2 fatty acids + phosphate head) and cholesterol (four fused rings), focusing on the amphipathic property of phospholipids that drives spontaneous bilayer self-assembly in water, and cholesterol's role as a membrane fluidity buffer. The content connects directly forward to Module 2.1.5 (biological membranes) (refer to the official OCR H420 specification document for exact wording).

Lipids are not only energy stores — they are essential components of every biological membrane. This lesson focuses on phospholipids and cholesterol, the two lipid classes that define the structure and properties of the cell surface membrane and internal membranes.

1. Phospholipids — the Building Blocks of Membranes

A phospholipid is similar to a triglyceride, but with one key difference: one of the three fatty acids is replaced by a phosphate group. The result is a molecule with two hydrocarbon tails and a phosphate-containing head.

Key Definition — Phospholipid: A lipid molecule composed of glycerol, two fatty acid tails, and a phosphate group (often attached to a further polar group). It is amphipathic — having both hydrophilic and hydrophobic regions.

1.1 Structure

Glycerol backbone — three carbons
Two fatty acid tails (can be saturated or unsaturated)
Phosphate group on the third carbon of glycerol; typically bonded to an additional polar group such as choline (giving phosphatidylcholine, the commonest phospholipid in animal membranes)
Three ester bonds in total: two between fatty acids and glycerol, one between phosphate and glycerol (also called a phosphoester bond)

1.2 Amphipathic Nature

The phosphate head is charged and polar, so it is hydrophilic — it forms hydrogen bonds with water.

The two fatty acid tails are non-polar hydrocarbons, so they are hydrophobic — they repel water but interact favourably with other non-polar molecules.

A molecule with both hydrophilic and hydrophobic regions is called amphipathic (or amphiphilic). This dual nature is the reason phospholipids spontaneously form membranes.

2. Phospholipid Behaviour in Water

When phospholipids are placed in water, they spontaneously organise themselves to minimise unfavourable interactions between water and the hydrophobic tails. Several arrangements are possible:

2.1 Monolayer

At the air-water interface, phospholipids form a single layer with heads in the water and tails projecting into the air.

2.2 Micelle

In the bulk of water, phospholipids can form micelles — small spherical clusters with tails in the core and heads facing outward.

2.3 Bilayer (Membrane)

The most biologically important arrangement is the phospholipid bilayer. Two layers of phospholipids orient with their heads facing the watery environments on each side of the membrane and their tails buried in the centre of the bilayer, shielded from water.

This bilayer structure is the fundamental architecture of all biological membranes, including the plasma membrane, nuclear envelope, endoplasmic reticulum, Golgi apparatus, mitochondrial membranes and thylakoid membranes.

2.4 Fluid Mosaic Model

Phospholipid molecules in a bilayer are not fixed — they can move laterally within each layer, giving the membrane a fluid quality (like a two-dimensional liquid). Proteins are embedded in or attached to the bilayer, creating the fluid mosaic model of membrane structure (Singer and Nicolson, 1972).

2.5 Role of Unsaturated Fatty Acids

Unsaturated fatty acid tails have kinks (due to C=C double bonds) that prevent tight packing.
Membranes with more unsaturated phospholipids are more fluid.
Organisms in cold environments (e.g., Arctic fish) have more unsaturated fatty acids in their membranes to maintain fluidity at low temperatures.

3. Biological Functions of Phospholipids

Form membranes — bilayer structure is the backbone of every biological membrane.
Barrier to water-soluble molecules — polar and charged molecules cannot cross the hydrophobic core without assistance.
Allow selective transport — in conjunction with embedded transport proteins.
Cell signalling — specific phospholipids (e.g., phosphatidylinositol) generate second messengers.
Lung surfactant — phospholipids lining alveoli reduce surface tension, preventing collapse.

4. Cholesterol — a Membrane Steroid

Cholesterol is a steroid lipid — it belongs to a class of lipids with a characteristic four-fused-ring structure. It is not built from glycerol and fatty acids, so it is structurally very different from triglycerides and phospholipids. Nevertheless, it plays crucial roles in animal cell membranes.

4.1 Structure

Cholesterol consists of:

Four fused hydrocarbon rings (three six-membered and one five-membered) — the steroid backbone.
A short hydrocarbon tail at one end.
A single hydroxyl group (–OH) at the other end, providing a small hydrophilic region.

The hydroxyl group makes cholesterol weakly amphipathic: mostly hydrophobic but with one polar end. This allows cholesterol to orient itself within a phospholipid bilayer with the –OH close to the phosphate heads and the rest of the molecule buried among the fatty acid tails.

4.2 Roles of Cholesterol in Membranes

Cholesterol has two main structural roles, both related to membrane fluidity:

At high temperatures: cholesterol reduces fluidity by binding to adjacent phospholipid tails and restricting their movement. This prevents the membrane from becoming too fluid or leaky.
At low temperatures: cholesterol maintains fluidity by preventing fatty acid tails from packing too tightly together. This stops the membrane from becoming rigid and cracked in the cold.

Cholesterol therefore acts as a fluidity buffer, keeping the membrane at a stable fluidity across a range of temperatures.

4.3 Other Roles of Cholesterol

Beyond its membrane role, cholesterol is the precursor for:

Steroid hormones — testosterone, oestrogen, progesterone, cortisol, aldosterone.
Bile salts — emulsify fats in the small intestine.
Vitamin D — synthesised in the skin from a cholesterol derivative by UV light.

4.4 Cholesterol and Health

While cholesterol is essential, excess blood cholesterol — especially as low-density lipoprotein (LDL) — is associated with the build-up of plaques in artery walls (atherosclerosis) and increased risk of coronary heart disease and stroke. High-density lipoprotein (HDL) cholesterol is considered protective because it transports cholesterol back to the liver for excretion.

5. Comparing Triglycerides, Phospholipids and Cholesterol

Feature	Triglyceride	Phospholipid	Cholesterol
Glycerol backbone?	Yes	Yes	No
Fatty acids	3	2	0
Phosphate group?	No	Yes	No
Hydrophilic/hydrophobic	Entirely hydrophobic	Amphipathic	Mostly hydrophobic, small polar –OH
Bonds	3 ester	2 ester + 1 phosphoester	Fused ring structure
Main role	Energy storage	Membrane structure	Membrane fluidity + steroid precursor

graph TD
  L[Lipids] --> T["Triglycerides<br/>glycerol + 3 fatty acids"]
  L --> P["Phospholipids<br/>glycerol + 2 fatty acids + phosphate"]
  L --> S["Steroids<br/>4 fused rings"]
  T --> T1[Energy storage]
  P --> P1[Membrane bilayer]
  S --> S1["Cholesterol<br/>membrane fluidity"]
  S --> S2[Steroid hormones]
  S --> S3[Bile salts, Vitamin D]

6. Experimental Identification of Lipids — the Emulsion Test

The emulsion test is the standard biochemical test for lipids:

Dissolve the sample in absolute ethanol (lipids are soluble in ethanol).
Add an equal volume of water and shake.
A white, cloudy emulsion indicates the presence of lipids.

The principle: ethanol extracts lipids from the sample; when water is added, the lipid comes out of solution as tiny droplets that scatter light, producing the cloudiness. The test is qualitative, not quantitative.

Lesson 7: Phospholipids and Cholesterol