Fatty acids

Fatty acidsFatty acids, both free and as part of complex lipids, play a number of key roles in metabolism

major metabolic fuelstorage and transport of energy as essential components of all membranes gene regulators

In addition,dietary lipids provide polyunsaturated fatty acids that are precursors of powerful locally acting metabolites, i.e. the eicosanoids.

As part of complex lipids, fatty acids are also important for thermal and electrical insulation, and for mechanical protection.

Moreover, free fatty acids and their salts may function as detergents and soaps owing to their amphipathic properties and the formation of micelles.

Structure of fatty acidsFatty acids are synthesized from linear acetogenins of acetate pathwayFatty acids are carbon chains with a methyl group at one end of the molecule (designated omega, ) and a carboxyl group at the other end.

The carbon atom next to the carboxyl group is called the carbon, and the subsequent one the carbonThe systematic nomenclature for fatty acids may also indicate the location of double bonds with reference to the carboxyl group ().

CH3 (CH2 )n CH2 CH2 COOH

Fatty acids may be named according to systematic or trivial nomenclature.

One systematic way to describe fatty acids is related to the methyl () end. This is used to describe the position of double bonds from the end of the fatty acid.

Classification Fatty acids are classified depending on the saturation

01) Saturated fatty acidsSaturated fatty acids are filled (saturated) with hydrogen no double bondsMost saturated fatty acids are straight hydrocarbon chains with an even number of carbon atoms. The most common fatty acids contain 1222 carbon atoms.

Unsaturated fatty acids

Monounsaturated fatty acids have one carboncarbon double bond, which can occur in different positions. The most common monoenes have a chain length of 1622 and a double bond with the cis configuration.

This means that the hydrogen atoms on either side of the double bond are oriented in the same direction. Trans isomers may be produced during industrial processing (hydrogenation) of unsaturated oils and in the gastrointestinal tract of ruminants.

Short chain saturated fatty acids Bad smellFluidsPresent in milk fat (C4-C10)Easily digestible

Long chain saturated fatty acids Solid at room temperature Most common in animal and plant fats Less easily digestible

The presence of a double bond causes restriction in the mobility of the acyl chain at that point.

Cis fatty acids are thermodynamically less stable than the trans forms.

The cis fatty acids have lower melting points than the trans fatty acids or their saturated counterparts.

In polyunsaturated fatty acids (PUFAs) the first double bond may be found between the third and the fourth carbon atom from the carbon; these are called -3 fatty acids. If the first double bond is between the sixth and seventh carbon atom, then they are called -6 fatty acids.The double bonds in PUFAs are separated from each other by a methylene grouping.

PUFAs, which are produced only by plants and phytoplankton,are essential to all higher organisms, including mammals and fish. -3 and -6 fatty acids cannot be interconverted, and both are essential nutrients. PUFAs are further metabolized in the body by the addition of carbon atoms and by desaturation (extraction of hydrogen).

Mammals have desaturases that are capable of removing hydrogens only from carbon atoms between an existing double bond and the carboxyl group . -oxidation of fatty acids may take place in either mitochondria or peroxisomes.

Physical propertiesFatty acids are poorly soluble in water in their undissociated (acidic) form, whereas they are relatively stable as potassium or sodium salts

Thus, the actual water solubility, particularly of longer-chain acids, is often very difficult to determine since it is markedly influenced by pH

Fatty acids are easily extracted with nonpolar solvents from solutions or suspensions by lowering the pH to form the uncharged carboxyl group.

In contrast, raising the pH increases water solubility through the formation of alkali metal salts, which are familiar as soaps.

Soaps have important properties as association colloids and are surface active Agents.

Physical Properties of Saturated Fatty AcidsSaturated fatty acids have:Molecules that fit closely together in a regular patternStrong attractions (dispersion forces) between fatty acid chainsHigh melting points that makes them solids at room temperature.

Physical Properties of Unsaturated Fatty AcidsUnsaturated fatty acids have:Nonlinear chains that do not allow molecules to pack closelyWeak attractions (dispersion forces) between fatty acid chainsLow melting points and so are liquids at room temperature

TriacylglycerolsTriacylglycerols (also called triglycerides) are tri-fatty acid esters of glycerolTriacylglycerols are the major form of fatty acid storage in plants and animalsTriacylglycerols can be classified as fats or oils- fats are solid at room temperature and most come from animals- oils are usually liquid at room temperature and come from plants (palm and coconut oils are solids at room temperature)

Hydrogenation converts alkenes to alkanesSo, hydrogenation of unsaturated oils produces saturated fatsHydrogenation is typically carried out by bubbling H2 gas through the heated oil, in the presence of a metal catalyst (such as nickel or platinum)Unsaturated oils are usually only partially hydrogenated, so that the product is not completely saturated, giving a soft semisolid fat such as margarine

Hydrogenation of Unsaturated Oils

Cis and Trans Unsaturated Fatty AcidsNatural unsaturated fatty acids have cis double bondsWhen unsaturated vegetable oils are hydrogenated to form more saturated oils (as in margarine), some of the cis fatty acids are isomerized to trans fatty acids

Trans fatty acids are much more linear than cis fatty acids, so their melting points are higher and studies have shown that trans fats may act similarly to saturated fats and could contribute to heart disease and some cancers

Nomenclature of fatty acids Systematic name: SATURATED: parent hydrocarbon + oic e.g. C18: Octadecanoic acid

UNSATURATED: with one double bond: + enoic e.g. C18: Octadecenoic acid with two double bonds: + dienoic e.g.C18: Octadecadienoic acid with three double bonds: + trienoic e.g. C18: Octadecatrienoic acid

Saturated Common SystematicC16:0 Palmitic n-HexadecanoicC18:0 Stearic n-Octadecanoic

Unsaturated Common SystematicC16:1(9) Palmitoleic cis-9-HexadecenoicC18:2(9,12) Linoleic cis-9,trans-12 - OctadecadienoicC18:3(9,12,15) Linolenic all cis-9,12,15- Octadecatrienoic

UNSATURATED counting from carboxy end methyl () end:C16:1(9) Palmitoleic 16:1, n-7 (7)C18:1(9) Oleic 18:1, n-9 (9)C18:2(9,12) Linoleic 18:2, n-6 (6)C18:3(9,12,15) Linolenic 18:3, n-3 (3)C20:4(5,8,11,14) Arachidonic20:4, n-6 (6)

AvailabilityOver half of the fatty acid residues of plant and animal lipids are unsaturated and are often polyunsaturated.

Bacterial fatty acid residues are rarely polyunsaturated but are commonly branched, hydroxylated, or contain cyclopropane rings.

Unusual fatty acids such as hydroxy fatty acids also occur as components of the oils and waxes (esters of FAs and long chain alcohols) produced by certain plants.

There are more than 100 different FAs in nature and most FAs have an even number of carbon atoms (mainly due to the mechanism of biosynthesis-the concatenation of C2 units)

Mainly present in the form of esters (not free)

In higher plants and animals, the predominant FA residues are those of the C16 and C18 species(palmitic, oleic, linoleic, and stearic acids).

FAs with less than 14 and more than 20 carbonatoms are uncommon

BRANCHED FAs

Of plant origin, not synthesized in mammalian organismsE.g. Phytanic acid (in cow milk) oxidation product of phytol(part of chlorophyl) 3,7,11,15 Tetramethylhexadecanoic acid In sebaceous glands

Failure to degrade phytanic acid - Refsum disease: deposits of the phytanic acid can be found in the nervous system neurological disorders of cerebellum, periferal nerves,eyes Prevention: phytanic acid-free food

Metabolism of fatty acidsLipolysisis carried out by lipases.Once freed from glycerol, free fatty acids can enter blood and muscle fiber by diffusion.Beta oxidation splits long carbon chains of the fatty acid into acetyl CoA, which can eventually enter the TCA cycle generates energy

Briefly, -oxidation or lipolysis of free fatty acids is as follows:Dehydrogenation by acyl-CoA dehydrogenase, yielding 1 FADH2Hydration by enoyl-CoA hydratase

Dehydrogenation by 3-hydroxyacyl-CoA dehydrogenase, yielding 1 NADHCleavage by thiolase, yielding 1 acetyl-CoA and a fatty acid that has now been shortened by 2 carbons (acyl-CoA)

This cycle repeats until the FFA has been completely reduced to acetyl-CoA or, in the case of fatty acids with odd numbers of carbon atoms, acetyl-CoA and 1mol of propionyl-CoA per mol of fatty acid.

Lipid peroxidationLipid peroxidation refers to the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism.

It most often affects polyunsaturated fatty acids, because they contain multiple double bonds in between which lie methylene bridges (-CH2-) that possess especially reactive hydrogens

As with any radical reaction, the reaction consists of three major steps: initiation, propagation, and termination.

If not terminated fast enough, there will be damage to the cell membrane, which consists mainly of lipids. Phototherapy may cause hemolysis by rupturing red blood cell membranes in this way.In addition, end-products of lipid peroxidation may be mutagenic and carcinogenic.

For instance, the end-product malondialdehyde reacts with deoxyadenosine and deoxyguanosine in DNA, forming DNA adducts to them

Oxidation of Unsaturated OilsFats and oils can become rancid in two ways:- bacterial ester hydrolysis - air oxidation of alkenesOxidation of fatty acid alkenes involves cleavage of the double bonds to form short-chain carboxylic acidsThese oxidation products are foul-tasting and smell badly

Fats and oils contain ester groups which can be hydrolyzed with aqueous acid, aqueous base (saponification) or enzymesThe hydrolysis products are glycerol and three fatty acidsWhen triacylglycerols containing short-chain fatty acids are hydrolyzed the carboxylic acid products (such as butanoic and hexanoic acids) are foul-smelling and foul-tasting (rancid)

SaponificationWhen a triacylglycerol is hydrolyzed with a strong base the process is called saponificationThe products of saponification are glycerol and fatty acid salts (soap)- NaOH is used with saturated fats to produce hard soaps- KOH is used with unsaturated fats to produce softer, more liquid soaps

Uses of fatty acidsFatty acids are widely used as inactive ingredients in drug preparations, and the use of lipid formulations as the carriers for active substances is growing rapidly. The largest amount of lipids used in pharmaceuticals is in the production of fat emulsions, mainly for clinical nutrition but also as drug vehicles.

Another lipid formulation is the liposome, which is a lipid carrier particle for other active ingredients. In addition, there has been an increase in the use of lipids as formulation ingredients