Fatty acid

In

chemistry

, particularly in

biochemistry

, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are a major component of the lipids (up to 70 wt%) in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of

ester

s:

triglyceride

s,

phospholipid

s, and cholesteryl esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and important structural components for cells.

History

The concept of fatty acid (''acide gras'') was introduced in 1813 by

Michel Eugène Chevreul

, though he initially used some variant terms: ''graisse acide'' and ''acide huileux'' ("acid fat" and "oily acid").

Types of fatty acids

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

Length of fatty acids

*Short-chain fatty acids (SCFA) are fatty acids with aliphatic tails of five or fewer

carbon

s (e.g.

butyric acid

).
*Medium-chain fatty acids (MCFA) are fatty acids with aliphatic tails of 6 to 12 carbons, which can form medium-chain triglycerides.
*Long-chain fatty acids (LCFA) are fatty acids with aliphatic tails of 13 to 21 carbons.
*Very long chain fatty acids (VLCFA) are fatty acids with aliphatic tails of 22 or more carbons.

Saturated fatty acids

Saturated fatty acids have no C=C double bonds. They have the same formula CH(CH)COOH, with variations in "n". An important saturated fatty acid is

stearic acid

(n = 16), which when neutralized with lye is the most common form of

soap

.

Unsaturated fatty acids

Unsaturated fatty acids have one or more C=C

double bond

s. The C=C double bonds can give either ''cis'' or ''trans'' isomers.

; ''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.

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'' : 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-3), six ( n-6), or nine ( n-9) carbon atoms after it, and all double bonds have a cis configuration. Most fatty acids in the ''trans'' 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 of ruminants (such as cattle and sheep). They are produced, by fermentation, in the rumen of these animals. They are also found in dairy products from milk of ruminants, and may be also found in breast 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).

Even- vs odd-chained fatty acids

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

and

heptadecanoic acid

respectively, which are found in dairy products. On a molecular level, OCFAs are biosynthesized and metabolized slightly differently from the even-chained relatives.

Nomenclature

Carbon atom numbering

Most naturally occurring fatty acids have an unbranched chain of carbon atoms, with a

carboxyl group

(–COOH) at one end, and a

methyl group

(–CH3) at the other end.

The position of the carbon atoms in the backbone of a fatty acid are usually indicated by counting from 1 at the −COOH end. Carbon number ''x'' is often abbreviated C-''x'' (or sometimes C''x''), with ''x'' = 1, 2, 3, etc. This is the numbering scheme recommended by the IUPAC.

Another convention uses letters of the

Greek alphabet

in sequence, starting with the first carbon ''after'' the carboxyl. 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.A common mistake is to say that the last carbon is "ω−1".
Another common mistake is to say that the position of a bond in omega-notation is the number of the carbon closest to the END.
For double bonds, these two mistakes happen to compensate each other; so that a "ω−3" fatty acid indeed has the double bond between the 3rd and 4th carbons from the end, counting the methyl as 1.
However, for substitutions and other purposes, they don't: a hydroxyl "at ω−3" is on carbon 15 (4th from the end), not 16. See for example this article.
Note also that the "−" in the omega-notation is a minus sign, and "ω−3" should in principle be read "omega minus three". However, it is very common (especially in non-scientific literature) to write it "ω-3" (with a hyphen/dash) and read it as "omega-three". See for example Karen Dooley (2008)
Omega-three fatty acids and diabetes

In either numbering scheme, the position of a

double bond

in a fatty acid chain is always specified by giving the label of the carbon closest to the carboxyl end. 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 positions ''x'',''y'',.... (The capital Greek letter "Δ" (delta) corresponds to

Roman

"D", for Double bond). Thus, for example, the 20-carbon

arachidonic 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 to the ω carbon (only), even in the case of multiple double bonds such as the essential fatty acids. Thus

linoleic 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 their formula ends with –CH=CH–––––.

Fatty acids with an odd number of carbon atoms are called odd-chain fatty acids, whereas the rest are even-chain fatty acids. The difference is relevant to gluconeogenesis.

Naming of fatty acids

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

Free fatty acids

When circulating in the plasma (plasma fatty acids), not in their

ester

, fatty acids are known as non-esterified fatty acids (NEFAs) or free fatty acids (FFAs). FFAs are always bound to a transport protein, such as albumin.

FFAs also form from

triglyceride

food oils and fats by hydrolysis, contributing to the characteristic rancid odor. An analogous process happens in

biodiesel

with risk of part corrosion.

Production

Industrial

Fatty acids are usually produced industrially by the

hydrolysis

of

triglyceride

s, with the removal of glycerol (see oleochemicals).

Phospholipid

s represent another source. Some fatty acids are produced synthetically by hydrocarboxylation of alkenes.

Hyper-oxygenated fatty acids

Hyper-oxygenated fatty acids are produced by a specific industrial processes for topical skin creams. The process is based on the introduction or saturation of peroxides into fatty acid esters via the presence of ultraviolet light and gaseous oxygen bubbling under controlled temperatures. Specifically linolenic acids have been shown to play an important role in maintaining the moisture barrier function of the skin (preventing water loss and skin dehydration). A study in Spain reported in the Journal of Wound Care in March 2005 compared a commercial product with a greasy

placebo

and that specific product was more effective and also cost-effective. A range of such OTC medical products is now widely available. However, topically applied

olive oil

was not found to be inferior in a " randomised triple-blind controlled non-inferiority" trial conducted in Spain during 2015. Commercial products are likely to be less messy to handle and more washable than either olive oil or petroleum jelly, both of which if applied topically may stain clothing and bedding.

By animals

In animals, fatty acids are formed from carbohydrates predominantly in the

liver

,

adipose tissue

, and the mammary glands during lactation.

Carbohydrates are converted into

pyruvate

by

glycolysis

as the first important step in the conversion of carbohydrates into fatty acids. Pyruvate is then decarboxylated to form

acetyl-CoA

in the

mitochondrion

. However, this acetyl CoA needs to be transported into cytosol where the synthesis of fatty acids occurs. This cannot occur directly. To obtain cytosolic acetyl-CoA,

citrate

(produced by the condensation of acetyl-CoA with

oxaloacetate

) is removed from the

citric acid cycle

and carried across the inner mitochondrial membrane into the cytosol. There it is cleaved by ATP citrate lyase into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to the mitochondrion as malate. The cytosolic acetyl-CoA is carboxylated by acetyl CoA carboxylase into

malonyl-CoA

, the first committed step in the synthesis of fatty acids.

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 form

triglyceride

s, the main storage form of fatty acids, and thus of energy in animals. However, fatty acids are also important components of the

phospholipid

s that form the phospholipid bilayers out of which all the membranes of the cell are constructed (the cell wall, and the membranes that enclose all the organelles within the cells, such as the

nucleus

, the

mitochondria

, endoplasmic reticulum, and the

Golgi apparatus

).

The "uncombined fatty acids" or "free fatty acids" found in the circulation of animals come from the breakdown (or lipolysis) of stored triglycerides. Because they are insoluble in water, these fatty acids are transported bound to plasma albumin. 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 the

central nervous system

). Fatty acids can only be broken down in mitochondria, by means of beta-oxidation followed by further combustion in the

citric acid cycle

to CO and water. Cells in the central nervous system, although they possess mitochondria, cannot take free fatty acids up from the blood, as the blood-brain barrier is impervious to most free fatty acids, excluding short-chain fatty acids and medium-chain fatty acids. 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.

Variation between animal species

Studies on the

cell membrane

s of mammals and

reptile

s discovered that mammalian cell membranes are composed of a higher proportion of polyunsaturated fatty acids (

DHA

, omega-3 fatty acid) than

reptile

s. Studies on bird fatty acid composition have noted similar proportions to mammals but with 1/3rd less omega-3 fatty acids as compared to omega-6 for a given body size. This fatty acid composition results in a more fluid cell membrane but also one that is permeable to various ions ( & ), 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 concomitant warm-bloodedness of mammals and birds. However polyunsaturation of cell membranes may also occur in response to chronic cold temperatures as well. In

fish

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 lower

temperature

s.

Fatty acids in dietary fats

The following table gives the fatty acid,

vitamin E

and

cholesterol

composition of some common dietary fats.

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 p''K''.

Nonanoic acid

, for example, has a p''K'' 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 the

pH

of an aqueous solution. Near neutral pH, fatty acids exist at their conjugate bases, i.e. oleate, etc.

Solutions of fatty acids in

ethanol

can be

titrated

with

sodium hydroxide

solution using

phenolphthalein

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 been

hydrolyze

d.

Neutralization of fatty acids, one form of

saponification

(soap-making), is a widely practiced route to metallic soaps.

Hydrogenation and hardening

Hydrogenation

of unsaturated fatty acids is widely practiced. Typical conditions involve 2.0–3.0 MPa of H pressure, 150 °C, and nickel supported on silica as a catalyst. This treatment affords saturated fatty acids. The extent of hydrogenation is indicated by the iodine number. Hydrogenated fatty acids are less prone toward rancidification. Since the saturated fatty acids are

higher melting

than the unsaturated precursors, the process is called hardening. Related technology is used to convert vegetable oils into

margarine

. 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 from ''cis'' to ''trans'' configuration.

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

ester

s.

In the Varrentrapp reaction certain unsaturated fatty acids are cleaved in molten alkali, a reaction which was, at one point of time, relevant 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 to a small degree 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

((CH)(COH)) from

oleic acid

.

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 reassemble again into

triglyceride

s. 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 are broken down to CO and water by the intra-cellular

mitochondria

through beta oxidation and the

citric acid cycle

. In the final step (

oxidative phosphorylation

), reaction with energy-rich oxygen releases a lot of energy, captured in the form of large quantities of

ATP

. Many cell types can use either

glucose

or fatty acids for this purpose, but fatty acids release more energy per gram because they contain less oxygen and therefore unlock the energy of more O. 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.

Essential fatty acids

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 bond three carbon atoms away from the methyl end; the other has a double bond six 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. Two essential fatty acids are

linoleic acid

(LA) and

alpha-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-chain omega-3 fatty acids — eicosapentaenoic acid (EPA) and

docosahexaenoic acid

(DHA), which can also be obtained from fish. Omega-3 and omega-6 fatty acids are

biosynthetic

precursors to endocannabinoids with antinociceptive, anxiolytic, and

neurogenic

properties.

Distribution

Blood fatty acids adopt distinct forms in different stages in the blood circulation. They are taken in through the intestine in

chylomicron

s, 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.

Analysis

The chemical analysis of fatty acids in lipids typically begins with an

interesterification

step that breaks down their original esters (triglycerides, waxes, phospholipids etc) and converts them to methyl esters, which are then separated by gas chromatography. or analyzed by gas chromatography and mid-infrared spectroscopy.

Separation of unsaturated isomers is possible by Argentation chromatography, silver ion complemented thin-layer chromatography. Other separation techniques include high-performance liquid chromatography (with short columns packed with silica 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.

Industrial uses

Fatty acids are mainly used in the production of

soap

, both for cosmetic purposes and, in the case of metallic soaps, as lubricants. Fatty acids are also converted, via their methyl esters, to fatty alcohols and fatty amines, which are precursors to surfactants, detergents, and lubricants. Other applications include their use as Emulsion#Emulsifiers, emulsifiers, texturizing agents, wetting agents, Defoamer, anti-foam agents, or stabilizing agents.

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 as sorbitol, ethylene glycol, diethylene glycol, and polyethylene glycol are consumed in food, or used for personal care and water treatment, or used as synthetic lubricants or fluids for metal working.

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''Prostaglandins, Leukotrienes & Essential Fatty Acids'' journal

{{DEFAULTSORT:Fatty Acid
Fatty acids,
Commodity chemicals
E-number additives