Fatty Acids

In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail (chain), which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of four to 28 carbons. The number of carbon atoms is usually even, because their biosynthesis involves acetyl-CoA, a coenzyme carrying a two-carbon-atom group (see fatty acid synthesis). Fatty acids are produced by the hydrolysis of the ester linkages in a fat or biological oil (both of which are triglycerides), with the removal of glycerol. See oleochemicals.

Fatty acids are aliphatic monocarboxylic acids derived from, or contained in esterified form in, an animal or vegetable fat, oil, or wax. By extension, the term is sometimes used to embrace all acyclic aliphatic carboxylic acids. This would include acetic acid, which is not usually considered a fatty acid because it is so short that the triglyceride triacetin made from it is substantially miscible with water and is thus not a lipid.

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

Fatty acids can be saturated and unsaturated, depending on double bonds. They differ in length as well.

Unsaturated fatty acids resemble saturated fatty acids, except that the chain has one or more double-bonds.

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.

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).

Saturated fatty acids are long-chain carboxylic acids that usually have between 12 and 24 carbon atoms and 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).

Fatty acids that are required by the body, but cannot be made in sufficient quantity by the body from other substrates, therefore must be obtained from food and are called essential fatty acids. In the body, essential fatty acids are primarily used to produce hormone-like substances that regulate a wide range of functions, including blood pressure, blood clotting, blood lipid levels, the immune response, and the inflammation response to injury infection.

The human body can produce all but two of the fatty acids it needs. These two, linoleic acid (LA) and alpha-linolenic acid (ALA), are widely distributed in plant oils. In addition, fish, flax, and hemp oils contain the longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Other marine oils, such as from seal, also contain significant amounts of docosapentaenoic acid (DPA), which is also an omega-3 fatty acid. Although the body to some extent can convert ALA into these longer-chain omega-3 fatty acids, the omega-3 fatty acids found in marine oils help fulfill the requirement for these essential fatty acids.

Essential fatty acids are polyunsaturated fatty acids and are the parent compounds of the omega-6 and omega-3 fatty acid series, respectively. They are essential in the human diet because, like all mammals, they lack the ability to introduce double bonds in fatty acids beyond carbons 9 and 10, as counted from the carboxylic acid side, because they do not have the enzymes necessary to introduce a double bond at the omega-3 position or omega-6 position. Humans can easily make saturated fatty acids or monounsaturated fatty acids with a double bond at the omega-9 position.

The essential fatty acids are important in several human body systems, including the immune system and in blood pressure regulation, since they are used to make compounds such as prostaglandins. The brain has increased amounts of linoleic and alpha-linolenic acid derivatives. Changes in the levels and balance of these fatty acids due to a typical Western diet rich in omega-6 and poor in omega-3 fatty acids is alleged to be associated with depression and behavioral change, including violence. The actual connection, if any, is still under investigation. Further, changing to a diet richer in omega-3 fatty acids, or consumption of supplements to compensate for a dietary imbalance, has been associated with reduced violent behavior and increased attention span, but the mechanisms for the effect are still unclear. So far, at least three human studies have shown results that support this: two school studies as well as a double blind study in a prison.

Fatty acids play an important role in the life and death of cardiac cells because they are essential fuels for mechanical and electrical activities of the heart.

A trans fatty acid (commonly shortened to trans fat) is an unsaturated fatty acid molecule that contains a trans double bond between carbon atoms, which makes the molecule less 'kinked' in comparison to fatty acids with cis double bonds. These bonds are characteristically produced during industrial hydrogenation of vegetable oils. Since they are also produced in bacterial metabolism, ruminant fats (e.g. in milk) also contain about 4% trans fatty acids. Research suggests that amounts of trans fats correlate with circulatory diseases such as atherosclerosis and coronary heart disease more than the same amount of cis fats, for reasons that are not fully understood. It is known, however, that trans fats, just like saturated fats, raise the LDL ("bad") cholesterol and lowers the HDL ("good") cholesterol. They have also been shown to have other harmful effects such as increasing triglycerides and Lp(a) lipoproteins. They are also thought to cause more inflammation, which is thought to occur through damage to the cells lining of blood vessels.

In addition to saturation, fatty acids are short, medium, or long.

When discussing essential fatty acids (EFA), a slightly different terminology applies. Short-chain EFA are 18 carbons long; long-chain EFA have 20 or more carbons.

There are several different systems of nomenclature in use for fatty acids. The following table describes the most common systems.

Fatty acids can be bound or attached to other molecules, such as in triglycerides or phospholipids. When they are not attached to other molecules, they are known as "free" fatty acids.

The uncombined fatty acids or free fatty acids may come from the breakdown of a triglyceride into its components (fatty acids and glycerol). However, as fats are insoluble in water, they must be bound to appropriate regions in the plasma protein albumin for transport around the body. The levels of "free fatty acid" in the blood are limited by the number of albumin binding sites available.

Free fatty acids are an important source of fuel for many tissues since they can yield relatively 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. The brain cannot use fatty acids as a source of fuel; it relies on glucose, or on ketone bodies. Ketone bodies are produced in the liver by fatty acid metabolism during periods of fasting, starvation, or otherwise low carbohydrate intake.

The following table gives the fatty acid, vitamin E and cholesterol composition of some common dietary fats.

Short-chain carboxylic acids such as formic acid and acetic acid are miscible with water and dissociate to form reasonably strong acids (pKa 3.77 and 4.76, respectively). Longer-chain fatty acids do not show a great change in pKa. Nonanoic acid, for example, has a pKa of 4.96. However, as the chain length increases the solubility of the fatty acids in water decreases very rapidly, so that the longer-chain fatty acids have very little effect on the pH of a solution. The significance of their pKa values therefore has relevance only to the types of reactions in which they can take part.

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.

Fatty acids react just like any other carboxylic acid, which means they can undergo esterification and acid-base reactions. Reduction of fatty acids yields fatty alcohols. Unsaturated fatty acids can also undergo addition reactions, most commonly hydrogenation, which is used to convert vegetable oils into margarine. With partial hydrogenation, unsaturated fatty acids can be isomerized from cis to trans configuration. In the Varrentrapp reaction certain unsaturated fatty acids are cleaved in molten alkali, a reaction at one time of relevance to structure elucidation.

Fatty acids at room temperature undergo a chemical change known as auto-oxidation. The fatty acid breaks down into hydrocarbons, ketones, aldehydes, and smaller amounts of epoxides and alcohols. Heavy metals present at low levels in fats and oils promote auto-oxidation. Fats and oils often are treated with chelating agents such as citric acid.

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 too large to be directly released into the tiny intestine 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.

Within the villi, the chylomicron enters 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 where they are needed.

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.