Basic Biochemistry of Fatty Acids
Physiologically Relevant Fatty Acids
Omega-3, and -6, Polyunsaturated Fatty Acids
Basic Structure of Complex Lipids
Triacylglycerides
Phospholipids
Plasmalogens
Sphingolipids
Metabolism of Lipids
Triacylglycerides
Phospholipids
Sphingolipids
Eicosanoids
Cholesterol and Bile Acids
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Major Roles of Biological Lipids
Biological molecules that are insoluble in aqueous solutions and soluble in organic solvents are classified as lipids. The lipids of physiological importance for humans have four major functions:1. They serve as structural components of biological membranes.
2. They provide energy reserves, predominantly in the form of triacylglycerols.
3. Both lipids and lipid derivatives serve as vitamins and hormones.
4. Lipophilic bile acids aid in lipid solubilization.
back to the topFatty Acids
Fatty acids fill two major roles in the body:
1. as the components of more complex membrane lipids.
2. as the major components of stored fat in the form of triacylglycerols.
Fatty acids are long-chain hydrocarbon molecules containing a carboxylic acid moiety at one end. The numbering of carbons in fatty acids begins with the carbon of the carboxylate group. At physiological pH, the carboxyl group is readily ionized, rendering a negative charge onto fatty acids in bodily fluids.
Fatty acids that contain no carbon-carbon double bonds are termed saturated fatty acids; those that contain double bonds are unsaturated fatty acids and fatty acids with multiple sites of unsaturation are termed polyunsaturated fatty acids (PUFAs). The numeric designations used for fatty acids come from the number of carbon atoms, followed by the number of sites of unsaturation (eg, palmitic acid is a 16-carbon fatty acid with no unsaturation and is designated by 16:0).
Palmitic Acid
The site of unsaturation in a fatty acid is indicated by the symbol Δ and the number of the first carbon of the double bond relative to the carboxylic acid group (–COOH) carbon which is designated carbon #1. For example, palmitoleic acid is a 16-carbon fatty acid with one site of unsaturation between carbons 9 and 10, and is designated by 16:1Δ9.
Saturated fatty acids of less than eight carbon atoms are liquid at physiological temperature, whereas those containing more than ten are solid. The presence of double bonds in fatty acids significantly lowers the melting point relative to a saturated fatty acid.
The majority of fatty acids found in the body are acquired in the diet. However, the lipid biosynthetic capacity of the body (fatty acid synthase and other fatty acid modifying enzymes) can supply the body with all the various fatty acid structures needed. Two key exceptions to this are the PUFAs known as linoleic acid and α-linolenic acid, containing unsaturation sites beyond carbons 9 and 10 (relative to the α-COOH group). These two fatty acids cannot be synthesized from precursors in the body, and are thus considered the essential fatty acids; essential in the sense that they must be provided in the diet. Since plants are capable of synthesizing linoleic and α-linolenic acid, humans can acquire these fats by consuming a variety of plants or else by eating the meat of animals that have consumed these plant fats. These two essential fatty acids are also referred to as omega fatty acids. The use of the greek omega, ω, refers to the end of the fatty acid opposite to that of the –COOH group. Linoleic acid is an omega-6 PUFA and α-linolenic is an omega-3 PUFA (see Table below). The role of PUFAs, such as linoleic and α-linolenic, in the synthesis of biologically important lipids is described briefly below and also in the Lipid Synthesis page and the Aspirin page.
back to the topPhysiologically Relevant Fatty Acids
| Numerical Symbol | Common Name and Struture | Comments |
| 14:0 | Myristic acid |
Often found attached to the N-term. of plasma membrane-associated cytoplasmic proteins |
| 16:0 | Palmitic acid |
End product of mammalian fatty acid synthesis |
| 16:1Δ9 | Palmitoleic acid |
|
| 18:0 | Stearic acid |
|
| 18:1Δ9 | Oleic acid |
An omega-9 monounsaturated fatty acid |
| 18:2Δ9,12 | Linoleic acid |
Essential fatty acid An omega-6 polyunsaturated fatty acid |
| 18:3Δ9,12,15 | α-Linolenic acid (ALA) |
Essential fatty acid An omega-3 polyunsaturated fatty acid |
| 20:4Δ5,8,11,14 | Arachidonic acid |
An omega-6 polyunsaturated fatty acid Precursor for eicosanoid synthesis |
| 20:5Δ5,8,11,14,17 | Eicosapentaenoic acid (EPA) |
An omega-3 polyunsaturated fatty acid enriched in fish oils |
| 22:6Δ4,7,10,13,16,19 | Docosahexaenoic acid (DHA) |
An omega-3 polyunsaturated fatty acid enriched in fish oils |
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Omega-3, and -6, Polyunsaturated Fatty Acids (PUFAs)
The term omega, as it relates to fatty acids, refers to the terminal carbon atom farthest from the functional carboxylic acid group (–COOH). The designation of a polyunsaturated fatty acid (PUFA) as an omega-3 fatty acid, for example, defines the position of the first site of unsaturation relative to the omega end of that fatty acid . Thus, an omega-3 fatty acid like α-linolenic acid (ALA), which harbors three carbon-carbon double bonds (i.e sites of unsaturation), has a site of unsaturation between the third and fourth carbons from the omega end (see Figure in Table above). There are three major types of omega-3 fatty acids that are ingested in foods and used by the body: ALA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Once eaten, the body converts ALA to EPA and DHA, the two types of omega-3 fatty acids more readily used by the body and which serve as important precursors for lipid-derived modulators of cell signaling, gene expression and inflammatory processes.
It is important to denote that when discussing omega-3 fatty acids, their dietary origin is quite important. Omega-3 fats from plants, such as those in flax seed oil, are enriched in ALA. As indicated above, ALA must first be converted to EPA (requiring three independent reactions) and then to DHA (requiring and additional four reactions). Omega-3 fats from fish are enriched in EPA and DHA and thus do not need to undergo the complex conversion steps required of ALA. In addition, the conversion of ALA to EPA and DHA is inefficient in individuals consuming a typical Western diet rich in animal fats.
Most of the omega-6 PUFAs consumed in the diet are from vegetable oils and consist of linoleic acid. Linoleic acid is converted to γ-linolenic acid (GLA) in the body. GLA should not be confused with ALA which, as pointed out above, is an essential omega-3 PUFA. GLA is then then further converted to arachidonic acid (as shown in the Lipid Synthesis page). GLA can be ingested from several plant-based oils including evening primrose oil, borage oil, and black currant seed oil.
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Basic Structure of Triacylglycerides
Triacylglycerides are composed of a glycerol backbone to which 3 fatty acids are esterified.
Basic Composition of a Triacylglyceride.
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Basic Structure of Phospholipids
The basic structure of phospolipids is very similar to that of the triacylglycerides except that C–3 (sn3)of the glycerol backbone is esterified to phosphoric acid. The building block of the phospholipids is phosphatidic acid which results when the X substitution in the basic structure shown in the Figure below is a hydrogen atom. Substitutions include ethanolamine (phosphatidylethanolamine), choline (phosphatidylcholine, also called lecithins), serine (phosphatidylserine), glycerol (phosphatidylglycerol), myo-inositol (phosphatidylinositol, these compounds can have a variety in the numbers of inositol alcohols that are phosphorylated generating polyphosphatidylinositols), and phosphatidylglycerol (diphosphatidylglycerol more commonly known as cardiolipins). See the Lipid Synthesis page for images of the various phospholipids.
Basic Composition of a Phospholipid.
X can be a number of different substituents.
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Basic Structure of Plasmalogens
Plasmalogens are complex membrane lipids that resemble phospholipids, principally phosphatidylcholine. The major difference is that the fatty acid at C–1 (sn1) of glycerol contains either an O-alkyl (–O–CH2–) or O-alkenyl ether (–O–CH=CH–) species. A basic O-alkenyl ether species is shown in the Figure below where –X can be substituents such as those found in phospholipids described above.
Basic Composition of O-Alkenyl Plasmalogens
One of the most potent alkyl ether plasmalogens is platelet activating factor (PAF: 1-O-1'-enyl-2-acetyl-sn-glycero-3-phosphocholine) which is a choline plasmalogen in which the C–2 (sn2) position of glycerol is esterified with an acetyl group instead of a long chain fatty acid.
PAF functions as a mediator of hypersensitivity, acute inflammatory reactions and anaphylactic shock. PAF is synthesized in response to the formation of antigen-IgE complexes on the surfaces of basophils, neutrophils, eosinophils, macrophages and monocytes. The synthesis and release of PAF from cells leads to platelet aggregation and the release of serotonin from platelets. PAF also produces responses in liver, heart, smooth muscle, and uterine and lung tissues.
Structure of PAF
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Basic Structure of Sphingolipids
Sphingolipids are composed of a backbone of sphingosine which is derived itself from glycerol. Sphingosine is N-acetylated by a variety of fatty acids generating a family of molecules referred to as ceramides. Sphingolipids predominate in the myelin sheath of nerve fibers. Sphingomyelin is an abundant sphingolipid generated by transfer of the phosphocholine moiety of phosphatidylcholine to a ceramide, thus sphingomyelin is a unique form of a phospholipid.
The other major class of sphingolipids (besides the sphingomyelins) are the glycosphingolipids generated by substitution of carbohydrates to the sn1 carbon of the glycerol backbone of a ceramide. There are 4 major classes of glycosphingolipids:
Cerebrosides: contain a single moiety, principally galactose.
Sulfatides: sulfuric acid esters of galactocerebrosides.
Globosides: contain 2 or more sugars.
Gangliosides: similar to globosides except also contain sialic acid.
"n" indicates any fatty acid may be N-acetylated at this position.
Top: Sphingosine
Bottom: Basic composition of a ceramide
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Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu
