Fatty acid

Comparison of the trans isomer Elaidic acid (top) and the cis isomer oleic acid (bottom).

In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with a long aliphatic tail (chain), which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 12 to 28.^[1] Fatty acids are usually derived from triglycerides or phospholipids. When they are not attached to other molecules, they are known as "free" fatty acids. Fatty acids are important sources of fuel because, when metabolized, they yield large quantities of ATP. Many cell types can use either glucose or fatty acids for this purpose. In particular, heart and skeletal muscle prefer fatty acids. Despite long-standing assertions to the contrary, fatty acids can be used as a source of fuel for brain cells, at least in some rodents,^[2][3] in addition to glucose and ketone bodies.

Types of fatty acids

Three-dimensional representations of several fatty acids

Fatty acids that have carbon–carbon double bonds are known as unsaturated. Fatty acids without double bonds are known as saturated. They differ in length as well.

Length of free fatty acid chains

Fatty acid chains differ by length, often categorized as short to very long.

• Short-chain fatty acids (SCFA) are fatty acids with aliphatic tails of fewer than six carbons (e.g. butyric acid).^[4]
• Medium-chain fatty acids (MCFA) are fatty acids with aliphatic tails of 6–12^[5] carbons, which can form medium-chain triglycerides.
• Long-chain fatty acids (LCFA) are fatty acids with aliphatic tails 13 to 21 carbons.^[6]
• Very long chain fatty acids (VLCFA) are fatty acids with aliphatic tails longer than 22 carbons.

Unsaturated fatty acids

Unsaturated fatty acids have one or more double bonds between carbon atoms. (Pairs of carbon atoms connected by double bonds can be saturated by adding hydrogen atoms to them, converting the double bonds to single bonds. Therefore, the double bonds are called unsaturated.)

The two carbon atoms in the chain that are bound next to either side of the double bond can occur in a cis or trans configuration.

cis

A cis configuration means that the two hydrogen atoms adjacent to the double bond stick out on the same side of the chain. The rigidity of the double bond freezes its conformation and, in the case of the cis isomer, causes the chain to bend and restricts the conformational freedom of the fatty acid. The more double bonds the chain has in the cis configuration, the less flexibility it has. When a chain has many cis bonds, it becomes quite curved in its most accessible conformations. For example, oleic acid, with one double bond, has a "kink" in it, whereas linoleic acid, with two double bonds, has a more pronounced bend. Alpha-linolenic acid, with three double bonds, favors a hooked shape. The effect of this is that, in restricted environments, such as when fatty acids are part of a phospholipid in a lipid bilayer, or triglycerides in lipid droplets, cis bonds limit the ability of fatty acids to be closely packed, and therefore can affect the melting temperature of the membrane or of the fat.

trans

A trans configuration, by contrast, means that the adjacent two hydrogen atoms lie on opposite sides of the chain. As a result, they do not cause the chain to bend much, and their shape is similar to straight saturated fatty acids.

In most naturally occurring unsaturated fatty acids, each double bond has three n carbon atoms after it, for some n, and all are cis bonds. Most fatty acids in the trans configuration (trans fats) are not found in nature and are the result of human processing (e.g., hydrogenation).

The differences in geometry between the various types of unsaturated fatty acids, as well as between saturated and unsaturated fatty acids, play an important role in biological processes, and in the construction of biological structures (such as cell membranes).

Essential fatty acids

Fatty acids that are required by the human body but cannot be made in sufficient quantity from other substrates, and therefore must be obtained from food, are called essential fatty acids. There are two series of essential fatty acids: one has a double bond three carbon atoms removed from the methyl end; the other has a double bond six carbon atoms removed from the methyl end. Humans lack the ability to introduce double bonds in fatty acids beyond carbons 9 and 10, as counted from the carboxylic acid side.^[7] Two essential fatty acids are linoleic acid (LA) and alpha-linolenic acid (ALA). They are widely distributed in plant oils. The human body has a limited ability to convert ALA into the longer-chain n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which can also be obtained from fish.

Saturated fatty acids

Saturated fatty acids have no double bonds. Thus, saturated fatty acids are saturated with hydrogen (since double bonds reduce the number of hydrogens on each carbon). Because saturated fatty acids have only single bonds, each carbon atom within the chain has 2 hydrogen atoms (except for the omega carbon at the end that has 3 hydrogens).

Arachidic acid, a saturated fatty acid.

Nomenclature

Numbering of carbon atoms

Several different systems of nomenclature are used for fatty acids. The following table describes the most common systems.

Production

Fatty acids are usually produced industrially by the hydrolysis of triglycerides, with the removal of glycerol (see oleochemicals). Phospholipids represent another source. Some fatty acids are produced synthetically by hydrocarboxylation of alkenes.

Free fatty acids

The biosynthesis of fatty acids involves the condensation of acetyl-CoA. Since this coenzyme carries a two-carbon-atom group, almost all natural fatty acids have even numbers of carbon atoms.

The "uncombined fatty acids" or "free fatty acids" found in organisms come from the breakdown of a triglyceride. Because they are insoluble in water, these fatty acids are transported (solubilized, circulated) while bound to plasma protein albumin. The levels of "free fatty acid" in the blood are limited by the availability of albumin binding sites.

Fatty acids in dietary fats

The following table gives the fatty acid, vitamin E and cholesterol composition of some common dietary fats.^{[10] [11]}

Reactions of fatty acids

Fatty acids exhibit reactions like other carboxylic acids, i.e. they undergo esterification and acid-base reactions.

Acidity

Fatty acids do not show a great variation in their acidities, as indicated by their respective pK_a. Nonanoic acid, for example, has a pK_a of 4.96, being only slightly weaker than acetic acid (4.76). As the chain length increases, the solubility of the fatty acids in water decreases very rapidly, so that the longer-chain fatty acids have minimal effect on the pH of an aqueous solution. Even those fatty acids that are insoluble in water will dissolve in warm ethanol, and can be titrated with sodium hydroxide solution using phenolphthalein as an indicator to a pale-pink endpoint. This analysis is used to determine the free fatty acid content of fats; i.e., the proportion of the triglycerides that have been hydrolyzed.

Hydrogenation and hardening

Hydrogenation of unsaturated fatty acids is widely practiced to give saturated fatty acids, which are less prone toward rancidification. Since the saturated fatty acids are higher melting than the unsaturated relatives, the process is called hardening. This technology is used to convert vegetable oils into margarine. During partial hydrogenation, unsaturated fatty acids can be isomerized from cis to trans configuration.^[13]

More forcing hydrogenation, i.e. using higher pressures of H₂ and higher temperatures, converts fatty acids into fatty alcohols. Fatty alcohols are, however, more easily produced from fatty acid esters.

In the Varrentrapp reaction certain unsaturated fatty acids are cleaved in molten alkali, a reaction at one time of relevance to structure elucidation.

Auto-oxidation and rancidity

Unsaturated fatty acids undergo a chemical change known as auto-oxidation. The process requires oxygen (air) and is accelerated by the presence of trace metals. Vegetable oils resist this process because they contain antioxidants, such as tocopherol. Fats and oils often are treated with chelating agents such as citric acid to remove the metal catalysts.

Ozonolysis

Unsaturated fatty acids are susceptible to degradation by ozone. This reaction is practiced in the production of azelaic acid ((CH₂)₇(CO₂H)₂) from oleic acid.^[13]

Analysis

In chemical analysis, fatty acids are separated by gas chromatography of methyl esters; additionally, a separation of unsaturated isomers is possible by argentation thin-layer chromatography.^[14]

Circulation

Digestion and intake

Short- and medium-chain fatty acids are absorbed directly into the blood via intestine capillaries and travel through the portal vein just as other absorbed nutrients do. However, long-chain fatty acids are not directly released into the intestinal capillaries. Instead they are absorbed into the fatty walls of the intestine villi and reassembled again into triglycerides. The triglycerides are coated with cholesterol and protein (protein coat) into a compound called a chylomicron.

From within the cell, the chylomicron is released into a lymphatic capillary called a lacteal, which merges into larger lymphatic vessels. It is transported via the lymphatic system and the thoracic duct up to a location near the heart (where the arteries and veins are larger). The thoracic duct empties the chylomicrons into the bloodstream via the left subclavian vein. At this point the chylomicrons can transport the triglycerides to tissues where they are stored or metabolized for energy.

Metabolism

Fatty acids (provided either by ingestion or by drawing on triglycerides stored in fatty tissues) are distributed to cells to serve as a fuel for muscular contraction and general metabolism. They are consumed by mitochondria to produce ATP through beta oxidation.

Distribution

Blood fatty acids are in different forms in different stages in the blood circulation. They are taken in through the intestine in chylomicrons, but also exist in very low density lipoproteins (VLDL) and low density lipoproteins (LDL) after processing in the liver. In addition, when released from adipocytes, fatty acids exist in the blood as free fatty acids.

It is proposed that the blend of fatty acids exuded by mammalian skin, together with lactic acid and pyruvic acid, is distinctive and enables animals with a keen sense of smell to differentiate individuals.^[15]

See also

• Fatty acid synthase
• Fatty acid synthesis
• Fatty aldehyde
• List of saturated fatty acids
• List of unsaturated fatty acids
• List of carboxylic acids
• Vegetable oil

References

External links

• Lipid Library
• JournalProstaglandins, Leukotrienes & Essential Fatty Acids
• Fatty Blood Acids