Introduction to fatty acids

Fatty acids (FA) are carboxylic acids with a hydrocarbon chain of varying length. The carboxyl group and the hydrocarbon chain determine the physical and chemical properties of the molecule.
In most cases the hydrocarbon chain is unbranched and with an even number of carbon atoms. It can contain only single bonds between carbon atoms, as in the case of saturated fatty acids, or at least one double or triple bonds between carbon atoms, as in the case of unsaturated fatty acids.
Fatty acids are members of the class of compounds known as lipids, and can be classified on the basis of chemical and physiological criteria, such as the length of the hydrocarbon chain, the presence or absence of double and triple bonds, the position of the double bonds with respect to the methyl end of the chain, the geometric isomerism or cis-trans isomerism of double bonds, or the ability to synthesize them.
In nature, they are rarely found in free form, and in that case they are known as free fatty acids (FFAs) or nonesterified fatty acids (NEFAs). In humans, there is a small amount of FFAs in the bloodstream, resulting from lipolysis; about three-fourths are bound to albumin, whereas one-fourth is bound to lipoproteins. Most commonly, fatty acids are bound through ester bonds to other organic molecules such as glycerol, glycerol 3-phosphate and sterols, to form more complex lipids, such as triglycerides, which are a major energy store in mammals, phospholipids, which are the major components of cell membranes, or sterol esters such as cholesterol esters.
They have important functions in cells. They can be oxidized to provide energy, they are components of cell membranes, being component of phospholipids, and are the precursors of bioactive lipid mediators.

CONTENTS

Structure and properties of fatty acids

Fatty acids are carboxylic acids with the general formula R–COOH, where R– is an hydrocarbon chain.
A carboxylic acid is an organic compound that contains a carboxyl functional group, −COOH, in which a carbon atom is bonded to an oxygen atom by a double bond, to form a carbonyl group, –C=O, and to an hydroxyl group, –OH, by a single bond. Carboxylic acids are weak acids. Their acidic nature results from the hydrogen of the carboxyl group and will be greater the shorter the hydrocarbon chain.
The R– group is attached to the fourth bond of the carboxylic carbon. R– group of formic acid, the simplest carboxyl acid, is a hydrogen atom, whereas in the other carboxyl acids it is an hydrocarbon chain that can be:

  • linear or branched;
  • with carbocyclic units;
  • with an even or odd number of carbon atoms;
  • without double/triple bonds between carbon atoms, therefore saturated;
  • with double/triple bonds between carbon atoms, therefore unsaturated.

Fatty acids found in foods almost always have a carbon chain with an even number of carbon atoms and a length of 4 to 24 atoms; moreover the chain can be saturated or unsaturated. For a list of the most important for human nutrition see the page List of fatty acids.
Branched FA are common in Gram-positive bacteria, and are present in low concentration in milk and meat lipids of ruminants.

Polarity

The carboxyl group is a polar acid group, whereas the hydrocarbon chain is the nonpolar region of the molecule. The hydrophobicity of the chain increases as the length increases, and this determines the degree of solubility of the fatty acid in polar and non-polar solvents.
In fatty acids with short carbon chain, the polarity of the carboxyl group wins over the hydrophobicity of the carbon chain, the molecule has a polar nature and is soluble in polar solvents such as water and ethanol. Butyric acid is an example of a fatty acid soluble in polar solvents.
As the length of the carbon chain increases, the solubility of the fatty acid in polar solvents decreases. Starting from caproic acid, whose chain is two carbons longer than that of butyric acid, the polarity gradually decreases with increasing chain length. Therefore, caprylic acid, with a 8 carbon atom chain, is less polar than capric acid, with a 10 carbon atom chain, wich in turn is less polar than lauric acid, with a 12 carbon atom chain. For chain length greater than 16-18 carbon atoms, therefore from palmitic acid and stearic acid forward, the molecules are completely insoluble in water. Examples are arachidic acidbehenic acid and lignoceric acid, three saturated FA with carbon chains of 20-, 22- and 24 carbon atoms.

Melting and boiling point

Like polarity, melting point and boiling point also depend on the properties of the carbon chain.
Melting and boiling points of saturated FA increase as the molecular weight increases, and therefore of the length of the chain. Saturated linear chains have a relatively linear configuration. This allows the molecules to pack closely together, which allows the formation of many intermolecular hydrophobic bonds that stabilize the structure in an almost crystalline form. This causes the increase in melting and boiling point.
Melting and boiling points of unsaturated FA are lower than the corresponding saturated FA. This is a consequence of differences in the geometry of the carbon chain due to the presence of double bonds.

Examples and skeletal formulas of saturated, unsaturated, conjugated and unconjugated fatty acidsThe double bond has a rigid planar structure and does not allow rotations between the two carbon atoms, which are possible in the single bond, and can be considered as a plane to which carbon chain attaches and continues, or enters and exits. If a part of the molecule has a rigid planar structure, the molecule can show geometric isomerism or cistrans isomerism. If the entry and exit of the chain from the plain occur on the same side, the double bond is in cis configuration, whereas if the entry and exit occur on opposite sides of the plain, the double bond is in trans configuration. Cis configuration causes a bend or “kink” in the carbon chain, as a result of which chains pack less efficiently than those of saturated FA, therefore establishing less intermolecular hydrophobic interactions. The resulting structure is less stable and less energy is needed to move the molecules away from each other. Hence, both the melting and boiling points of cis fatty acids will be lower than that of the corresponding saturated FA.
Trans configuration has a geometry similar to that of the single bond, and straightens the carbon chain giving it a shape similar to that of a saturated FA. Hence, molecules that have only trans double bonds pack with a similar efficiency to that of saturated FA, with which they have similar melting and boiling points.
The differences in the geometry between cis and trans double bonds and between saturated and unsaturated FA affect their biological functions; for example, saturated and trans FA form more rigid structures than cis fatty acids, and this affect the fluidity of biological membranes in which they are present.

Classification of fatty acids

There are several ways to classify fatty acids. As previously seen, they can be classified based on their polarity, or based on structural characteristics of the carbon chain.
A simple way is based on the even or odd number of carbon atoms of the chain.
Other ways are based on the presence or absence of branches or cyclic structures in the chain, on the length of carbon chain, on the presence or absence of double/triple bonds, on the geometric isomerism of the double bonds, on the number of double/triple bonds, on the position of the first double bond with respect to the methyl end of the chain, or on the geometric isomerism of the double bonds. In addition, they can be classified based on their essentiality for humans. Here are some examples.

Length of the carbon chain

In fatty acids with linear chain, chain length varies from one up to 30 and more carbon atoms.
Based on the length of the chain, they can be classified into:

  • short-chain fatty acids (SCFAs), in which chain length ranges from 1 to 5 carbons;
  • medium-chain fatty acids (MCFAs), in which chain length ranges from 6 to 12 carbons;
  • long-chain fatty acids (LCFAs), in which chain length ranges from 13 to 21 carbons;
  • very long chain fatty acids (VLCFAs), in which chain length is equal or greater than 22 carbons.

Saturated and unsaturated fatty acids

Based on the presence or absence of double/triple bonds in the carbon chain, they can be classified into:

  • saturated fatty acids, when there is no double/triple bond;
  • unsaturated fatty acids, when there is at least one double/triple bond.

Based on the number of double/triple bonds in the carbon chain, they can be classified into:

  • monounsaturated fatty acids, when there is only one double/triple bond;
  • polyunsaturated fatty acids, when there is more than one double/triple bond.

Unsaturated FA can be further classified based on the position of the first double bond with respect to the terminal methyl end of the chain.

Fatty acid is called acetylenic fatty acid when there is at least one triple bond in the carbon chain.

Polyunsaturated FA can be classified also based on the presence of conjugated double bond systems.

  • Conjugated fatty acids, when two or more double bonds are not separated by one or more methylene groups (–CH2–).
  • Unconjugated FA, when the double bonds in the chain are methylene-interrupted. Mainstream polyunsaturated fatty acids are unconjugated fatty acids.

Cis and trans isomers

Unsaturated FA containing double bonds can be classified based on the geometric isomerism into:

  • cis fatty acids, more common in nature and in food;
  • trans fatty acids, less common.
    In nature, trans FA are synthesized by bacteria in the rumen of ruminants from the unsaturated FA ingested by animals, and occur in their milk and meat. However, trans FA found in food are mainly a by-product of hydrogenation process of oils rich in unsaturated FA; these fatty acids are particularly deleterious to human health.

Oleic acid and elaidinic or elaidic acid are examples of cistrans isomerism: elaidic acid is the trans-isomer of oleic acid. Other trans FA found in food are vaccenic acid and brassidic acid.

Essential fatty acids

Fatty acids can be classified on a physiological basis, based on body’s ability to synthesize them. Two unsaturated FA, alpha-linolenic acid and linoleic acid, are classified as essential fatty acids as animals cannot synthesize them, lacking two desaturases: delta-12 desaturase (EC 1.14.19.6) and delta-15 desaturase (EC 1.14.19.13). Hence, they must be taken with food.

Functions

Fatty acids have many roles in the cell.
They are an energy source. After being released from intracellular triglycerides, they are oxidized to produce ATP within the cell itself or, if released from adipose tissue triglycerides, in the cells of other tissues and organs, mainly carried in the bloodstream by albumins. Liver, hearth and skeletal muscle are the main sites of oxidation. Cells obtain more energy from their oxidation than from the oxidation of carbohydrates and proteins, on average 9 kcal/g against 4 kcal/g of proteins and carbohydrates, although the oxidation of short-chain saturated FA yields less energy: for example, acetic acid, 3.5 kcal/g, propionic acid, 5.0 kcal/g of, butyric acid, 6.0 kcal/g, caproic acid, 7.5 kcal/g.
They are the precursors of potent bioactive lipid mediators that act as part of signal transduction pathways. Indeed, unsaturated FA such as arachidonic acid and docosahexaenoic acid, deriving from blood stream or released from membrane phospholipids, can be metabolized to potent pro-resolving lipid mediators, such as Lipoxins, Maresins, D-series Resolvins, and to pro-inflammatory lipid mediators, such as Prostaglandins and Leukotrienes.
They have a structural role in the formation of cell membranes, being a component of phospholipids which are key component of all biological membranes.

References

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  3. Chow Ching K. Fatty acids in foods and their health implication. 3th Edition. CRC Press, Taylor & Francis Group, 2008
  4. Evans H. M. and G. O. Burr. A new dietary deficiency with highly purified diets. III. The beneficial effect of fat in the diet. Proc Soc Exp Biol Med 1928;25:390-397. doi:10.3181/00379727-25-3867
  5. Mozaffarian D., Katan M.B., Ascherio A., Stampfer M.J., Willett W.C. Trans fatty acids and cardiovascular disease. N Engl J Med 2006;354:1601-1613. doi:10.1056/NEJMra054035
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Biochemistry, metabolism and nutrition