Olive oil, butter, the wax on an apple and cholesterol look nothing alike on paper. Yet none of them dissolves in water, and all of them dissolve in hexane, a nonpolar solvent. That shared behavior makes each of them a lipid: a molecule from a living thing that dissolves in nonpolar solvents and not in water.
Lipids are therefore the one class of biomolecule defined by a physical property rather than by a functional group. As a result, lipids come in very different structures. For most lipids, the shape of the molecule matters more than its functional group.
Fatty acids, and the kink that changes everything
Stearic acid, CH3(CH2)16COOH, is a chain of eighteen carbons with a carboxylic acid group at one end. It is a typical fatty acid: a carboxylic acid with a long, unbranched carbon chain, usually 12 to 20 carbons long.
Natural fatty acids almost always have an even number of carbons, because cells build the chain two carbons at a time. Each round is a Claisen condensation (see Claisen reactions).
Stearic acid has no C=C bonds, so it is saturated: every chain carbon carries as many hydrogens as it can. Oleic acid has the same eighteen carbons and one C=C, between C9 and C10. A fatty acid with one or more C=C bonds is unsaturated.
The double bond in oleic acid is cis: the two parts of the chain leave it on the same side (Cis/trans and E/Z). Nearly every unsaturated fatty acid in nature has cis double bonds, and that one fact explains how fats behave.
Reading the shorthand: Δ and ω numbers
Oleic acid is written 18:1 cis-Δ9, where Δ (delta) gives the carbon at which a double bond starts. Read it in order: eighteen carbons, one C=C, cis, starting at C9. The count starts at the carboxyl carbon, which is C1, so the double bond joins C9 and C10.
In the same shorthand, stearic acid is 18:0. Linoleic acid is 18:2 cis,cis-Δ9,12, with two cis double bonds starting at C9 and C12. α-Linolenic acid is 18:3 cis,cis,cis-Δ9,12,15.
The ω (omega) system counts from the other end, where the CH3 carbon is ω1. A fatty acid is called ω-n when the double bond nearest the CH3 end starts at ωn. In α-linolenic acid that double bond joins C15 and C16. Counted from the CH3 end, C16 is ω3, so α-linolenic acid is an ω-3 fatty acid.
You can convert without redrawing: subtract the Δ number of the last double bond from the number of carbons. For α-linolenic acid that is 18 − 15 = 3. For linoleic acid it is 18 − 12 = 6, so linoleic acid is an ω-6 acid, and oleic acid (18 − 9) is ω-9.
Shape sets the melting point
Stearic acid melts at 69 °C. Oleic acid has the same eighteen carbons but melts at 13 °C, so it is a liquid at room temperature. The one difference between them is a cis double bond.
Fatty acid chains attract each other by London dispersion forces, the weak attractions between nonpolar molecules described in Bond polarity. Each contact is weak, so the total depends on how much of one chain touches the next. Melting pulls the chains apart, and the more contact they have, the higher the melting point.
A saturated chain is straight, so neighboring chains lie flat against each other along their whole length. A cis double bond puts a permanent bend, or kink, in the chain. Kinked chains cannot line up, so they touch less and melt lower.
Each extra cis double bond adds another kink and lowers the melting point again. Linoleic acid, with two, melts at about −5 °C.
Elaidic acid is oleic acid with its double bond trans instead, so the two parts of the chain leave it on opposite sides. The chain stays nearly straight. Elaidic acid therefore packs almost like stearic acid and melts at 44 °C, although it has a double bond. The melting point follows the shape of the chain, not the number of double bonds.
Where trans fats come from
Most of the trans fat in processed food came from partial hydrogenation. Adding H2 over a nickel catalyst saturates some of the double bonds in a vegetable oil (a liquid fat whose chains are mostly cis-unsaturated) and hardens it. It is the reaction from Catalytic hydrogenation, stopped partway.
On the metal surface the two hydrogens do not arrive together. One H atom adds first and leaves a half-hydrogenated intermediate, in which one carbon has its new H and the other is still bonded to the metal. The C–C bond in this intermediate is single, and a single bond can rotate. From here the intermediate can take a second H and become saturated. Or the surface can take an H back and re-form the double bond. If the chain rotated first, the double bond comes back trans.
A partially hydrogenated oil therefore contains trans chains that were never saturated. They are still unsaturated, but they pack like saturated chains, so they raise the melting point too.
Triglycerides are triesters
Glycerol is propane-1,2,3-triol, HOCH2–CH(OH)–CH2OH: three carbons with an OH on each. Link each OH to a stearic acid through an ester, and you get glyceryl tristearate, also called tristearin. Each ester forms with loss of one water, so three waters leave in all.
Any glycerol carrying three fatty acids this way is a triglyceride (biochemists also say triacylglycerol). It is a triester, and it is the form in which living things store fatty acids for energy. Everything an ester does, a triglyceride does.
On paper, each ester is what a Fischer esterification of one OH with one acid would give (Nucleophilic acyl substitution). Cells take another route. They transfer each acyl group, the R–C=O part of the acid, from a thioester (an ester with S in place of the single-bonded O), the same activated acid derivative that fatty acid synthesis uses.
A natural fat is rarely made from one acid. One glycerol usually carries two or three different fatty acids, often a mix of saturated and unsaturated ones. So a single fat can behave partly as a solid and partly as an oil.
"Fat" and "oil" name physical states, not two kinds of compound. A triglyceride that is solid at room temperature is a fat, and one that is liquid is an oil. Which one it is depends on its chains. Butter is rich in saturated chains and is solid; olive oil is rich in cis-unsaturated chains and is liquid.
Saponification: soap from a fat
Heat tristearin with aqueous NaOH, and it breaks into glycerol and three molecules of sodium stearate, which is a soap. This reaction is saponification: the base hydrolysis of an ester, here run on all three esters of a triglyceride.
Each ester reacts by the base-promoted mechanism from Nucleophilic acyl substitution. Hydroxide adds to the carbonyl carbon and gives a tetrahedral intermediate. The intermediate collapses, and the glycerol oxygen leaves as an alkoxide. The alkoxide then takes the proton from the new carboxylic acid.
That last proton transfer drives the reaction to completion. A carboxylic acid is about ten pKa units more acidic than an alcohol, so the proton ends up on the alkoxide. The carboxylate left behind is a poor electrophile, and nothing attacks it, so the reaction cannot run backwards. Overall, each ester consumes one hydroxide, so each triglyceride consumes three.
A triglyceride carries one stearic, one oleic and one palmitic acid on its glycerol. It is refluxed with excess aqueous NaOH, and the mixture is then acidified. What comes out, and how much of each?
Count the esters. There are three, so there are three hydrolyses, and three hydroxides are used up.
Name the products before acidification. One glycerol and three different carboxylate salts: sodium stearate, sodium oleate and sodium palmitate, one of each. A soap made from a natural fat is a mixture for exactly this reason.
Then acidify. Acid protonates the three carboxylates and gives the three free fatty acids. These are no longer salts, so they no longer dissolve in water, and they separate from it as a greasy, partly solid layer. That is how acid destroys a soap, and it is why soap works badly in acidic water.
Soaps and micelles
Sodium stearate has two very different ends. The carboxylate end, –CO2− Na+, is ionic and dissolves in water. The seventeen-carbon tail is nonpolar and dissolves in grease. A molecule with one water-loving end and one water-avoiding end is amphipathic.
In water, soap molecules gather into a micelle: a sphere with the tails packed inside and the charged heads on the surface, facing the water. Grease dissolves in the nonpolar core. The micelle, grease and all, stays spread through the water and rinses away.
Phospholipids and the bilayer
Take a triglyceride and replace one of its end fatty acids with a phosphate group. Then link a small polar molecule, such as choline (HOCH2CH2N+(CH3)3), to the phosphate. The result is a phospholipid. The one drawn below, a phosphatidylcholine, belongs to the most common family of phospholipids in animal cell membranes.
A phospholipid has two nonpolar tails and one charged head. At pH 7 the phosphate carries a negative charge and the choline nitrogen a positive one. Like a soap, it is amphipathic, but it has two tails instead of one.
The second tail changes the structure the molecules form. One tail makes a soap molecule taper like a wedge, and wedges pack into a sphere. Two tails make a phospholipid roughly a cylinder, and cylinders pack into a flat sheet. Phospholipids therefore form a bilayer: two sheets of molecules, tail to tail, with heads facing the water on both sides. That bilayer is the basic structure of nearly every cell membrane.
No covalent bonds hold a micelle or a bilayer together. Water drives both, through the hydrophobic effect: water has to take up a more ordered arrangement around an exposed hydrocarbon surface, and hiding the tails frees that water. The same effect buries the nonpolar side chains inside a folded protein (Peptides and proteins).
Steroids: the other kind of lipid
Cholesterol, C27H46O, passes the lipid solubility test but shares no structure with a fatty acid. Its core is four rings fused together: three six-membered rings and one five-membered ring. Every steroid is built on this same four-ring skeleton.
The rings are lettered A to D, from the six-membered ring at the left to the five-membered ring at the right. The seventeen carbons of the skeleton are numbered from C1 in ring A round to C17 in ring D. A steroid's name is usually that fixed skeleton plus the positions of its oxygens, methyls and double bonds. Cholesterol has an OH on C3, a double bond from C5 to C6, methyls (C18 and C19) on C13 and C10, and an eight-carbon side chain on C17.
Cholesterol is the parent steroid in animals. It sits among the phospholipid tails of a membrane and moderates its fluidity. Its flat, rigid rings stiffen a membrane that would otherwise be too fluid, and they keep a cold membrane from setting solid.
Cells also make the steroid hormones from cholesterol. Two of them, testosterone and estradiol, differ only around ring A. The enzyme aromatase turns testosterone into estradiol. It removes C19, the methyl on C10, and makes ring A aromatic, so the ketone on C3 becomes the OH of a phenol.
Prostaglandins: fatty acids that signal
One more family is worth naming: the prostaglandins. They are C20 acids made from arachidonic acid (20:4, an ω-6 acid), and each carries a five-membered ring with two long side chains on it. They act as local signals for inflammation, pain and fever, rather than travelling through the blood as hormones do. Closely related C20 signals, the thromboxanes, make platelets clump when blood clots.
Aspirin blocks the enzyme that makes them: it moves its own acetyl group onto a serine OH in the enzyme. That is an acyl transfer from an ester, the same kind of reaction as saponification with a different nucleophile.
Waxes and terpenes
Beeswax is mostly esters, and its main ester joins a C16 acid to a C30 alcohol. A wax is the simplest ester lipid: one long-chain acid joined to one long-chain alcohol by a single ester.
The two long saturated chains pack well, and the one polar group is buried between them. The result is a hard, water-repellent solid, which is why waxes coat leaves, feathers and fruit. Hydrolyzing a wax gives exactly two products, an acid and an alcohol, in equal amounts.
Limonene, the smell of orange peel, has ten carbons. It is a terpene: a lipid whose carbon skeleton is built from five-carbon isoprene units. Isoprene is 2-methylbuta-1,3-diene, CH2=C(CH3)–CH=CH2, a four-carbon chain with a one-carbon branch on C2. Cells do not use isoprene itself; they build terpenes from five-carbon building blocks with the same branched skeleton.
Limonene is two isoprene units joined by two bonds. One bond joins the far end of one unit to the end next to the branch in the other. This link is called head to tail, and it is the usual one. The second bond closes the ring.
Because each unit brings five carbons, terpene carbon counts come in multiples of five. Menthol and limonene have ten. Squalene has thirty. Its two fifteen-carbon halves meet in the middle, where the same kind of end on each half is bonded to the other, not head to tail. Squalene is epoxidized and then closes into the four-ring steroid skeleton (as lanosterol, C30), which loses three carbons on the way to cholesterol's twenty-seven. Counting the carbons in fives is the fastest way to recognize a terpene.
Why fat is the storage molecule
Living things store energy as fat rather than as sugar, and the reason is oxidation level. A fatty acid chain is almost entirely CH2: each carbon has only C–H and C–C bonds and no bond to oxygen, which is as reduced as a carbon inside a chain can be (see Oxidation levels in organic chemistry). A carbohydrate already carries an oxygen on nearly every carbon. Burning fat to CO2 therefore releases much more energy: roughly twice as much per gram. Storing energy means storing reduced carbon, and a triglyceride is the most reduced carbon a cell can conveniently keep.
What carries forward
Two threads run through this page, and neither is new. The ester chemistry, formation and hydrolysis, is Carboxylic Acids & Derivatives applied to a large molecule. The shape argument, that cis chains cannot pack, is the dispersion-force reasoning from Bond polarity, here deciding whether a fat is butter or oil. The same packing argument returns for plastics in Polymers.