Inchemistry, particularly inbiochemistry, afatty acid is acarboxylic acid with analiphatic chain, which is eithersaturated or unsaturated. Most naturally occurring fatty acids have anunbranched chain of an even number of carbon atoms, from 4 to 28.^[1] Fatty acids are a major component of the lipids (up to 70% by weight) in some species such as microalgae^[2] but in some other organisms are not found in their standalone form, but instead exist as three main classes ofesters:triglycerides,phospholipids, andcholesteryl esters. In any of these forms, fatty acids are both importantdietary sources of fuel for animals and important structural components forcells.

The concept of fatty acid (acide gras) was introduced in 1813 byMichel Eugène Chevreul,^[3][4][5] though he initially used some variant terms:graisse acide andacide huileux ("acid fat" and "oily acid").^[6]

Fatty acids are classified in many ways: by length, by saturation vs unsaturation, by even vs odd carbon content, and by linear vs branched.

• Short-chain fatty acids (SCFAs) are fatty acids withaliphatic tails of five or fewercarbons (e.g.butyric acid).^[7]
• Medium-chain fatty acids (MCFAs) are fatty acids with aliphatic tails of 6 to 12^[8] carbons, which can formmedium-chain triglycerides.
• Long-chain fatty acids (LCFAs) are fatty acids with aliphatic tails of 13 to 21 carbons.^[9]
• Very long chain fatty acids (VLCFAs) are fatty acids with aliphatic tails of 22 or more carbons.

Saturated fatty acids have no C=C double bonds. They have the formula CH₃(CH₂)_nCOOH, wheren is some positive integer. An important saturated fatty acid isstearic acid (n = 16), which when neutralized withsodium hydroxide is the most common form ofsoap.

Unsaturated fatty acids have one or more C=Cdouble bonds. The C=C double bonds can give eithercis ortrans isomers.

cis

Acis 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 thecis isomer, causes the chain to bend and restricts the conformational freedom of the fatty acid. The more double bonds the chain has in thecis configuration, the less flexibility it has. When a chain has manycis bonds, it becomes quite curved in its most accessible conformations. For example,oleic acid, with one double bond, has a "kink" in it, whereaslinoleic acid, with two double bonds, has a more pronounced bend.α-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. Cis unsaturated fatty acids, however, increase cellular membrane fluidity, whereas trans unsaturated fatty acids do not.

trans

Atrans configuration, by contrast, means that the adjacent two hydrogen atoms lie onopposite 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−3), six (n−6), or nine (n−9) carbon atoms after it, and all double bonds have a cis configuration. Most fatty acids in thetrans configuration (trans fats) are not found in nature and are the result of human processing (e.g.,hydrogenation). Some trans fatty acids also occur naturally in the milk and meat ofruminants (such as cattle and sheep). They are produced, by fermentation, in the rumen of these animals. They are also found indairy products from milk of ruminants, and may be also found inbreast milk of women who obtained them from their diet.

The geometric differences 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).

Most fatty acids are even-chained, e.g. stearic (C18) and oleic (C18), meaning they are composed of an even number of carbon atoms. Some fatty acids have odd numbers of carbon atoms; they are referred to as odd-chained fatty acids (OCFA). The most common OCFA are the saturated C15 and C17 derivatives,pentadecanoic acid andheptadecanoic acid respectively, which are found in dairy products.^[11][12] On a molecular level, OCFAs are biosynthesized and metabolized slightly differently from the even-chained relatives.

Most common fatty acids arestraight-chain compounds, with no additional carbon atoms bonded asside groups to the main hydrocarbon chain.Branched-chain fatty acids contain one or moremethyl groups bonded to the hydrocarbon chain.

Most naturally occurring fatty acids have anunbranched chain of carbon atoms, with acarboxyl group (–COOH) at one end, and amethyl group (–CH3) at the other end.

The position of each carbon atom in the backbone of a fatty acid is usually indicated by counting from 1 at the −COOH end. Carbon numberx is often abbreviated C-x (or sometimes Cx), withx = 1, 2, 3, etc. This is the numbering scheme recommended by theIUPAC.

Another convention uses letters of theGreek alphabet in sequence, starting with the first carbonafter the carboxyl group. Thus carbon α (alpha) is C-2, carbon β (beta) is C-3, and so forth.

Although fatty acids can be of diverse lengths, in this second convention the last carbon in the chain is always labelled as ω (omega), which is the last letter in the Greek alphabet. A third numbering convention counts the carbons from that end, using the labels "ω", "ω−1", "ω−2". Alternatively, the label "ω−x" is written "n−x", where the "n" is meant to represent the number of carbons in the chain.^[d]

In either numbering scheme, the position of adouble bond in a fatty acid chain is always specified by giving the label of the carbon closest to thecarboxyl end.^[d] Thus, in an 18 carbon fatty acid, a double bond between C-12 (or ω−6) and C-13 (or ω−5) is said to be "at" position C-12 or ω−6. The IUPAC naming of the acid, such as "octadec-12-enoic acid" (or the more pronounceable variant "12-octadecanoic acid") is always based on the "C" numbering.

The notation Δ^x,y,... is traditionally used to specify a fatty acid with double bonds at positionsx,y,.... (The capital Greek letter "Δ" (delta) corresponds toRoman "D", forDouble bond). Thus, for example, the 20-carbonarachidonic acid is Δ^5,8,11,14, meaning that it has double bonds between carbons 5 and 6, 8 and 9, 11 and 12, and 14 and 15.

In the context of human diet and fat metabolism, unsaturated fatty acids are often classified by the position of the double bond closest between to the ω carbon (only), even in the case ofmultiple double bonds such as theessential fatty acids. Thuslinoleic acid (18 carbons, Δ^9,12),γ-linolenic acid (18-carbon, Δ^6,9,12), and arachidonic acid (20-carbon, Δ^5,8,11,14) are all classified as "ω−6" fatty acids; meaning that theirformula ends with –CH=CH–CH
₂–CH
₂–CH
₂–CH
₂–CH
₃.

Fatty acids with anodd number of carbon atoms are calledodd-chain fatty acids, whereas the rest are even-chain fatty acids. The difference isrelevant to gluconeogenesis.

The following table describes the most common systems of naming fatty acids.

Whencirculating in theplasma (plasma fatty acids), not in theirester, fatty acids are known as non-esterified fatty acids (NEFAs) or free fatty acids (FFAs). FFAs are always bound to atransport protein, such asalbumin.^[15]

FFAs also form fromtriglyceride food oils and fats by hydrolysis, contributing to the characteristicrancid odor.^[16] An analogous process happens inbiodiesel with risk of part corrosion.

Fatty acids are usually produced industrially by thehydrolysis oftriglycerides, with the removal ofglycerol (seeoleochemicals).Phospholipids represent another source. Some fatty acids are produced synthetically byhydrocarboxylation of alkenes.^[17]

In animals, fatty acids are formed from carbohydrates predominantly in theliver,adipose tissue, and themammary glands during lactation.^[18]

Carbohydrates are converted intopyruvate byglycolysis as the first important step in the conversion of carbohydrates into fatty acids.^[18] Pyruvate is then decarboxylated to formacetyl-CoA in themitochondrion. However, this acetyl CoA needs to be transported intocytosol where the synthesis of fatty acids occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA,citrate (produced by the condensation of acetyl-CoA withoxaloacetate) is removed from thecitric acid cycle and carried across the inner mitochondrial membrane into the cytosol.^[18] There it is cleaved byATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to the mitochondrion asmalate.^[19] The cytosolic acetyl-CoA is carboxylated byacetyl-CoA carboxylase intomalonyl-CoA, the first committed step in the synthesis of fatty acids.^[19][20]

Malonyl-CoA is then involved in a repeating series of reactions that lengthens the growing fatty acid chain by two carbons at a time. Almost all natural fatty acids, therefore, have even numbers of carbon atoms. When synthesis is complete the free fatty acids are nearly always combined with glycerol (three fatty acids to one glycerol molecule) to formtriglycerides, the main storage form of fatty acids, and thus of energy in animals. However, fatty acids are also important components of thephospholipids that form thephospholipid bilayers out of which all the membranes of the cell are constructed (thecell wall, and the membranes that enclose all theorganelles within the cells, such as thenucleus, themitochondria,endoplasmic reticulum, and theGolgi apparatus).^[18]

The "uncombined fatty acids" or "free fatty acids" found in the circulation of animals come from the breakdown (orlipolysis) of stored triglycerides.^[18][21] Because they are insoluble in water, these fatty acids are transported bound to plasmaalbumin. The levels of "free fatty acids" in the blood are limited by the availability of albumin binding sites. They can be taken up from the blood by all cells that have mitochondria (with the exception of the cells of thecentral nervous system). Fatty acids can only be broken down in mitochondria, by means ofbeta-oxidation followed by further combustion in thecitric acid cycle to CO₂ and water. Cells in the central nervous system, although they possess mitochondria, cannot take free fatty acids up from the blood, as theblood–brain barrier is impervious to most free fatty acids,^{[citation needed]} excludingshort-chain fatty acids andmedium-chain fatty acids.^[22][23] These cells have to manufacture their own fatty acids from carbohydrates, as described above, in order to produce and maintain the phospholipids of their cell membranes, and those of their organelles.^[18]

Studies on thecell membranes ofmammals andreptiles discovered that mammalian cell membranes are composed of a higher proportion of polyunsaturated fatty acids (DHA,omega−3 fatty acid) thanreptiles.^[24] Studies on bird fatty acid composition have noted similar proportions to mammals but with 1/3rd less omega−3 fatty acids as compared toomega−6 for a given body size.^[25] This fatty acid composition results in a more fluid cell membrane but also one that is permeable to various ions (H⁺ &Na⁺), resulting in cell membranes that are more costly to maintain. This maintenance cost has been argued to be one of the key causes for the high metabolic rates and concomitantwarm-bloodedness of mammals and birds.^[24] However polyunsaturation of cell membranes may also occur in response to chronic cold temperatures as well. Infish increasingly cold environments lead to increasingly high cell membrane content of both monounsaturated and polyunsaturated fatty acids, to maintain greater membrane fluidity (and functionality) at the lowertemperatures.^[26][27]

The following table gives the fatty acid,vitamin E andcholesterol composition of some common dietary fats.^[28][29]

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

All fatty acidstransesterify. Typically, transesterification is practiced in the conversion of fats to fatty acid methyl esters. These esters are used for biodiesel. They are also hydrogenated to give fatty alcohols. Even vinyl esters can be made by transesterification usingvinyl acetate.^[31]

Fatty acids do not show a great variation in their acidities, as indicated by their respectivepK_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, so that the longer-chain fatty acids have minimal effect on thepH of an aqueous solution. Near neutral pH, fatty acids exist at their conjugate bases, i.e. oleate, etc.

Solutions of fatty acids inethanol can betitrated withsodium hydroxide solution usingphenolphthalein as an indicator. This analysis is used to determine the free fatty acid content of fats; i.e., the proportion of the triglycerides that have beenhydrolyzed.

Neutralization of fatty acids, likesaponification, is a widely practiced route tometallic soaps.^[32]

Hydrogenation of unsaturated fatty acids is widely practiced. Typical conditions involve 2.0–3.0 MPa of H₂ pressure, 150 °C, and nickel supported on silica as a catalyst. This treatment affords saturated fatty acids. The extent of hydrogenation is indicated by theiodine number. Hydrogenated fatty acids are less prone towardrancidification. Since the saturated fatty acids arehigher melting than the unsaturated precursors, the process is called hardening. Related technology is used to convert vegetable oils intomargarine. The hydrogenation of triglycerides (vs fatty acids) is advantageous because the carboxylic acids degrade the nickel catalysts, affording nickel soaps. During partial hydrogenation, unsaturated fatty acids can be isomerized fromcis totrans configuration.^[17]

More forcing hydrogenation, i.e. using higher pressures of H₂ and higher temperatures, converts fatty acids intofatty alcohols. Fatty alcohols are, however, more easily produced from simpler fatty acidesters, like thefatty acid methyl esters ("FAME"s).

Ketonic decarboxylation is a method useful for producing symmetrical ketones from carboxylic acids. The process involves reactions of the carboxylic acid with an inorganic base. Stearone is prepared by heatingmagnesium stearate.^[33]

The reactivity of saturated fatty acids is usually associated with the carboxylic acid or the adjacent methylene group By conversion to their acid chlorides, they can be converted to the symmetrical fatty ketone laurone (O=C(C_nH_(2n+1))₂).^[34] Treatment withsulfur trioxide gives the α-sulfonic acids.^[35]

The reactivity of unsaturated fatty acids is often dominated by the site of unsaturation. These reactions are the basis of ozonolysis, hydrogenation, and the iodine number. Ozonolysis (degradation by ozone) is practiced in the production ofazelaic acid ((CH₂)₇(CO₂H)₂) fromoleic acid.^[17]

Short- andmedium-chain fatty acids are absorbed directly into the blood via intestine capillaries and travel through theportal 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 intestinevilli and reassemble again intotriglycerides. The triglycerides are coated withcholesterol and protein (protein coat) into a compound called achylomicron.

From within the cell, the chylomicron is released into alymphatic capillary called alacteal, which merges into larger lymphatic vessels. It is transported via the lymphatic system and thethoracic 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 leftsubclavian vein. At this point the chylomicrons can transport the triglycerides to tissues where they are stored or metabolized for energy.

Fatty acids are broken down to CO₂ and water by the intra-cellularmitochondria throughbeta oxidation and thecitric acid cycle. In the final step (oxidative phosphorylation), reactions with oxygen release a lot of energy, captured in the form of large quantities ofATP. Many cell types can use eitherglucose or fatty acids for this purpose, but fatty acids release more energy per gram. 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.

Fatty acids that are required for good health 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 bondthree carbon atoms away from the methyl end; the other has a double bondsix carbon atoms away 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.^[36] Two essential fatty acids arelinoleic acid (LA) andalpha-linolenic acid (ALA). These fatty acids are widely distributed in plant oils. The human body has a limited ability to convert ALA into the longer-chainomega-3 fatty acids —eicosapentaenoic acid (EPA) anddocosahexaenoic acid (DHA), which can also be obtained from fish. Omega−3 andomega−6 fatty acids arebiosynthetic precursors toendocannabinoids withantinociceptive,anxiolytic, andneurogenic properties.^[37]

Blood fatty acids adopt distinct forms in different stages in the blood circulation. They are taken in through the intestine inchylomicrons, but also exist invery low density lipoproteins (VLDL) andlow density lipoproteins (LDL) after processing in the liver. In addition, when released fromadipocytes, fatty acids exist in the blood asfree fatty acids.

It is proposed that the blend of fatty acids exuded by mammalian skin, together withlactic acid andpyruvic acid, is distinctive and enables animals with a keen sense of smell to differentiate individuals.^[38]

Thestratum corneum – the outermost layer of theepidermis – is composed of terminallydifferentiated andenucleatedcorneocytes within a lipid matrix.^[39] Together withcholesterol andceramides, free fatty acids form a water-impermeable barrier that preventsevaporative water loss.^[39] Generally, the epidermal lipid matrix is composed of an equimolar mixture of ceramides (about 50% by weight), cholesterol (25%), and free fatty acids (15%).^[39] Saturated fatty acids 16 and 18 carbons in length are the dominant types in the epidermis,^[39][40] while unsaturated fatty acids and saturated fatty acids of various other lengths are also present.^[39][40] The relative abundance of the different fatty acids in the epidermis is dependent on the body site the skin is covering.^[40] There are also characteristic epidermal fatty acid alterations that occur inpsoriasis,atopic dermatitis, and otherinflammatory conditions.^[39][40]

The chemical analysis of fatty acids in lipids typically begins with aninteresterification step that breaks down their original esters (triglycerides, waxes, phospholipids etc.) and converts them tomethyl esters, which are then separated by gas chromatography^[41] or analyzed bygas chromatography and mid-infrared spectroscopy.

Separation of unsaturated isomers is possible bysilver ion complemented thin-layer chromatography.^[42] Other separation techniques includehigh-performance liquid chromatography (with short columns packed withsilica gel with bonded phenylsulfonic acid groups whose hydrogen atoms have been exchanged for silver ions). The role of silver lies in its ability to form complexes with unsaturated compounds.

Fatty acids are mainly used in the production ofsoap, both for cosmetic purposes and, in the case ofmetallic soaps, as lubricants. Fatty acids are also converted, via their methyl esters, tofatty alcohols andfatty amines, which are precursors to surfactants, detergents, and lubricants.^[17] Other applications include their use asemulsifiers, texturizing agents, wetting agents,anti-foam agents, or stabilizing agents.^[43]

Esters of fatty acids with simpler alcohols (such as methyl-, ethyl-, n-propyl-, isopropyl- and butyl esters) are used as emollients in cosmetics and other personal care products and as synthetic lubricants. Esters of fatty acids with more complex alcohols, such assorbitol,ethylene glycol,diethylene glycol, andpolyethylene glycol are consumed in food, or used for personal care and water treatment, or used as synthetic lubricants or fluids for metal working.

• Lipid Library
• Prostaglandins, Leukotrienes & Essential Fatty Acids journal
• Fatty blood acids