Fatty acid

Fatty acids are fundamental organic molecules that play key roles in energy storage, membrane structure and metabolic regulation in living organisms. Chemically, they are carboxylic acids with long aliphatic hydrocarbon chains, which may be saturated (containing no carbon–carbon double bonds) or unsaturated (containing one or more double bonds). In biological systems, fatty acids rarely exist in isolation; they are typically incorporated into complex lipids such as triglycerides, phospholipids and cholesteryl esters. These compounds are vital both as dietary fuels and as structural components of cell membranes.

Definition and general structure

A fatty acid consists of:

• a terminal carboxyl group (–COOH) at one end, and
• a hydrophobic hydrocarbon chain at the other, terminating in a methyl group (–CH₃).

Most naturally occurring fatty acids have an even number of carbon atoms, typically between 4 and 28. This reflects their biosynthesis from two-carbon acetyl units. The hydrocarbon chain may be:

• saturated – containing only single C–C bonds, giving a straight chain;
• monounsaturated – containing one C=C double bond; or
• polyunsaturated – containing two or more C=C double bonds.

In lipids such as triglycerides and phospholipids, fatty acids are usually present as esters formed with glycerol or with other alcohol-containing backbones. In some organisms, particularly microalgae, fatty acids can make up a very high proportion of total lipid mass.

Historical background

The concept of the fatty acid as a distinct chemical class was introduced in the early nineteenth century. The term acide gras (fatty acid) was used to describe acidic constituents derived from fats and oils. Over time, as organic chemistry and biochemistry developed, fatty acids came to be recognised as central intermediates in metabolism, linking carbohydrate breakdown, lipid storage and energy production.

Classification by chain length

Fatty acids are commonly grouped by the length of their hydrocarbon chain:

• Short-chain fatty acids (SCFAs): up to 5 carbon atoms (for example, butyric acid, C₄).
• Medium-chain fatty acids (MCFAs): 6–12 carbon atoms; these can form medium-chain triglycerides with distinctive metabolic properties.
• Long-chain fatty acids (LCFAs): 13–21 carbon atoms, typical of many membrane and storage lipids.
• Very-long-chain fatty acids (VLCFAs): 22 or more carbon atoms, often found in specialised lipids such as those in myelin and certain sphingolipids.

Chain length influences solubility, melting point and how the fatty acid is handled in metabolism, including its absorption, transport and oxidation.

Saturated fatty acids

Saturated fatty acids contain no carbon–carbon double bonds. Their general formula is CH₃–(CH₂)ₙ–COOH, where n is a positive integer. The absence of double bonds permits maximal packing of the hydrocarbon chains, leading to relatively high melting points; as a result, fats rich in saturated fatty acids are often solid at room temperature.
An important example is stearic acid (C₁₈:0). When neutralised with sodium hydroxide, stearic acid forms a sodium salt that is a common component of traditional soaps. Saturated fatty acids often contribute to the structural rigidity of biological membranes and to the physical properties of stored fats.

Unsaturated fatty acids: cis and trans isomerism

Unsaturated fatty acids contain one or more C=C double bonds within the hydrocarbon chain. These double bonds introduce the possibility of cis–trans isomerism:

• In the cis configuration, the hydrogen atoms attached to the carbons of the double bond lie on the same side of the chain. This arrangement creates a kink or bend and reduces the ability of the chains to pack closely together.
• In the trans configuration, the hydrogens lie on opposite sides of the double bond, leaving the chain more extended and structurally similar to a saturated fatty acid.

The cis configuration predominates in naturally occurring unsaturated fatty acids. It has important consequences for membrane fluidity, because cis double bonds increase spacing between adjacent fatty acid chains, lowering melting temperature and enhancing fluidity in lipid bilayers.
By contrast, trans fatty acids, largely formed industrially by partial hydrogenation of vegetable oils, behave more like saturated fats and do not increase membrane fluidity. Some trans fatty acids occur naturally in small amounts in the fat and milk of ruminant animals, produced by microbial fermentation in the rumen.

Polyunsaturation and omega nomenclature

Polyunsaturated fatty acids (PUFAs) contain multiple double bonds, usually separated by a methylene (–CH₂–) group. The position of double bonds can be described in two main ways:

1. Δ (Delta) notation – counts from the carboxyl (COOH) end. For example, arachidonic acid (C₂₀) with double bonds at carbons 5, 8, 11 and 14 is written as 20:4Δ⁵,⁸,¹¹,¹⁴.
2. ω (omega) notation – counts from the methyl (CH₃) end. Omega-3 (ω-3), omega-6 (ω-6) and omega-9 (ω-9) fatty acids are defined by the position of the first double bond relative to this end.

In human nutrition and metabolism, ω-3 and ω-6 fatty acids are of particular interest. Examples include:

• Linoleic acid (C₁₈:2Δ⁹,¹²), an ω-6 fatty acid.
• γ-Linolenic acid (C₁₈:3Δ⁶,⁹,¹²), also ω-6.
• Arachidonic acid (C₂₀:4Δ⁵,⁸,¹¹,¹⁴), another ω-6 fatty acid.

These PUFAs are precursors to bioactive molecules such as eicosanoids, which influence inflammation, blood clotting and other physiological processes.

Even- and odd-chain fatty acids

Most fatty acids are even-chain, such as stearic acid (C₁₈:0) and oleic acid (C₁₈:1). This reflects their biosynthesis from two-carbon units of acetyl-CoA. However, some odd-chain fatty acids (OCFAs) do occur, typically with 15 or 17 carbon atoms, such as pentadecanoic acid (C₁₅:0) and heptadecanoic acid (C₁₇:0). These are found notably in dairy fat.
On a molecular level, OCFAs are synthesised and metabolised slightly differently from their even-chain counterparts, particularly in the final steps of β-oxidation, where propionyl-CoA rather than acetyl-CoA is produced and enters specific metabolic pathways, including gluconeogenesis.

Branched-chain fatty acids

While many common fatty acids are straight-chain, some possess one or more methyl branches along the hydrocarbon chain. These branched-chain fatty acids can influence packing, melting behaviour and the physical properties of lipids. They are found in certain bacteria, in some animal tissues, and in specialised lipids, and may alter membrane characteristics such as thickness and fluidity.

Nomenclature and numbering systems

Several systems are used to describe fatty acid structure:

• Carbon-number notation: Cx indicates a fatty acid with x carbon atoms, for example C₁₈.
• Δ notation: C₁₈:1Δ⁹ indicates 18 carbons, one double bond at carbon 9 from the COOH end.
• ω notation: an ω-3 fatty acid has its first double bond three carbons from the methyl end.

In systematic IUPAC nomenclature, fatty acids are named as derivatives of the corresponding alkanes. For instance, oleic acid can be named octadec-9-enoic acid. In all systems, the position of double bonds is specified by the carbon number closest to the carboxyl end.

Free fatty acids in the circulation

In biological fluids, fatty acids may exist as non-esterified fatty acids (NEFAs), often referred to as free fatty acids (FFAs). Despite the term “free”, these molecules are usually bound to plasma proteins, particularly albumin, which facilitates their transport in the bloodstream from adipose tissue to energy-requiring organs such as skeletal muscle and liver.
Hydrolysis of triglycerides in food oils and adipose tissue releases free fatty acids, a process that, in stored fats and oils, contributes to rancidification and characteristic odours. An analogous hydrolytic process in biodiesel can generate free fatty acids that may promote corrosion or instability of the fuel.

Industrial and biological production

Industrial production of fatty acids often involves hydrolysis of triglycerides derived from natural fats and oils, separating glycerol from fatty acid chains. These free fatty acids can then be purified and used in detergents, soaps, cosmetics, lubricants and as feedstock for further chemical synthesis. Additional synthetic routes include carbonylation of alkenes, which can generate tailored fatty acid structures for specific industrial applications.
In animals, fatty acid biosynthesis occurs mainly in the liver, adipose tissue and mammary glands (particularly during lactation). The key steps include:

• Conversion of carbohydrates to pyruvate via glycolysis.
• Decarboxylation of pyruvate to acetyl-CoA in the mitochondria.
• Transfer of acetyl units into the cytosol, often via citrate, to provide substrate for the fatty acid synthase complex.