Lipids

Lec. ( 8 ) Lipids

The lipids are a large and diverse group of naturally occurring organic compounds that are related by their solubility in nonpolar organic solvents (e.g. ether, chloroform, acetone & benzene) and general insolubility in water. There is great structural variety among the lipids, as will be demonstrated in the following sections.

Fats, Oils, Waxes & Phospholipids
1. Fatty Acids
The common feature of these lipids is that they are all esters of moderate to long chain fatty acids. Acid or base-catalyzed hydrolysis yields the component fatty acid, some examples of which are given in the following table, together with the alcohol component of the lipid. These long-chain carboxylic acids are generally referred to by their common names, which in most cases reflect their sources. Natural fatty acids may be saturated or unsaturated, and as the following data indicate, the saturated acids have higher melting points than unsaturated acids of corresponding size. The double bonds in the unsaturated compounds listed on the right are all cis (or Z).







FATTY ACIDS
Saturated
Formula Common Name Melting Point
CH3(CH2)10CO2H lauric acid 45 ?C
CH3(CH2)12CO2H myristic acid 55 ?C
CH3(CH2)14CO2H palmitic acid 63 ?C
CH3(CH2)16CO2H stearic acid 69 ?C
CH3(CH2)18CO2H arachidic acid 76 ?C
Unsaturated
Formula Common Name Melting Point
CH3(CH2)5CH=CH(CH2)7CO2H palmitoleic acid 0 ?C
CH3(CH2)7CH=CH(CH2)7CO2H oleic acid 13 ?C
CH3(CH2)4CH=CHCH2CH=CH(CH2)7CO2H linoleic acid -5 ?C
CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7CO2H linolenic acid -11 ?C
CH3(CH2)4(CH=CHCH2)4(CH2)2CO2H arachidonic acid -49 ?C


The higher melting points of the saturated fatty acids reflect the uniform rod-like shape of their molecules. The cis-double bond(s) in the unsaturated fatty acids introduce a kink in their shape, which makes it more difficult to pack their molecules together in a stable repeating array or crystalline lattice. The trans-double bond isomer of oleic acid, known as elaidic acid, has a linear shape and a melting point of 45 ?C (32 ?C higher than its cis isomer). The shapes of stearic and oleic acids are displayed in the models below. You may examine models of these compounds by clicking on the desired model picture.
2- Stearic acid & Oleic acid
Two polyunsaturated fatty acids, linoleic and linolenic, are designated "essential" because their absence in the human diet has been associated with health problems, such as scaley skin, stunted growth and increased dehydration. These acids are also precursors to the prostaglandins, a family of physiologically potent lipids present in minute amounts in most body tissues.
Because of their enhanced acidity, carboxylic acids react with bases to form ionic salts, as shown in the following equations. In the case of alkali metal hydroxides and simple amines (or ammonia) the resulting salts have pronounced ionic character and are usually soluble in water. Heavy metals such as silver, mercury and lead form salts having more covalent character (3rd example), and the water solubility is reduced, especially for acids composed of four or more carbon atoms.
RCO2H + NaHCO3
RCO2(–) Na(+) + CO2 + H2O
RCO2H + (CH3)3N:
RCO2(–) (CH3)3NH(+)
RCO2H + AgOH
RCO2?(–)Ag?(+) + H2O

3-Fats and Oils
The triesters of fatty acids with glycerol (1,2,3-trihydroxypropane) compose the class of lipids known as fats and oils. These triglycerides (or triacylglycerols) are found in both plants and animals, and compose one of the major food groups of our diet. Triglycerides that are solid or semisolid at room temperature are classified as fats, and occur predominantly in animals. Those triglycerides that are liquid are called oils and originate chiefly in plants, although triglycerides from fish are also largely oils. Some examples of the composition of triglycerides from various sources are given in the following table.
Saturated Acids (%) Unsaturated Acids (%)
Source C10
& less C12
lauric C14
myristic C16
palmitic C18
stearic C18
oleic C18
linoleic C18
unsaturated
Animal Fats
butter 15 2 11 30 9 27 4 1
lard - - 1 27 15 48 6 2
human fat - 1 3 25 8 46 10 3
herring oil - - 7 12 1 2 20 52
Plant Oils
coconut - 50 18 8 2 6 1 -
corn - - 1 10 3 50 34 -
olive - - - 7 2 85 5 -
palm - - 2 41 5 43 7 -
peanut - - - 8 3 56 26 7
safflower - - - 3 3 19 76 -
As might be expected from the properties of the fatty acids, fats have a predominance of saturated fatty acids, and oils are composed largely of unsaturated acids. Thus, the melting points of triglycerides reflect their composition, as shown by the following examples. Natural mixed triglycerides have somewhat lower melting points, the melting point of lard being near 30 ? C, whereas olive oil melts near -6 ? C. Since fats are valued over oils by some Northern European and North American populations, vegetable oils are extensively converted to solid triglycerides (e.g. Crisco) by partial hydrogenation of their unsaturated components. Some of the remaining double bonds are isomerized (to trans) in this operation. These saturated and trans-fatty acid glycerides in the diet have been linked to long-term health issues such as atherosclerosis.

Triglycerides having three identical acyl chains, such as tristearin and triolein (above), are called "simple", while those composed of different acyl chains are called "mixed". If the acyl chains at the end hydroxyl groups (1 & 3) of glycerol are different, the center carbon becomes a chiral center and enantiomeric configurations must be recognized.
The hydrogenation of vegetable oils to produce semisolid products has had unintended consequences. Although the hydrogenation imparts desirable features such as spreadability, texture, "mouth feel," and increased shelf life to naturally liquid vegetable oils, it introduces some serious health problems. These occur when the cis-double bonds in the fatty acid chains are not completely saturated in the hydrogenation process. The catalysts used to effect the addition of hydrogen isomerize the remaining double bonds to their trans configuration. These unnatural trans-fats appear to to be associated with increased heart disease, cancer, diabetes and obesity, as well as immune response and reproductive problems.

4. Waxes
Waxes are esters of fatty acids with long chain monohydric alcohols (one hydroxyl group). Natural waxes are often mixtures of such esters, and may also contain hydrocarbons. The formulas for three well known waxes are given below, with the carboxylic acid moiety colored red and the alcohol colored blue.
spermaceti beeswax carnuba wax
CH3(CH2)14CO2-(CH2)15CH3 CH3(CH2)24CO2-(CH2)29CH3 CH3(CH2)30CO2-(CH2)33CH3
Waxes are widely distributed in nature. The leaves and fruits of many plants have waxy coatings, which may protect them from dehydration and small predators. The feathers of birds and the fur of some animals have similar coatings which serve as a water repellent. Carnuba wax is valued for its toughness and water resistance.

5. Phospholipids
Phospholipids are the main constituents of cell membranes. They resemble the triglycerides in being ester or amide derivatives of glycerol or sphingosine with fatty acids and phosphoric acid. The phosphate moiety of the resulting phosphatidic acid is further esterified with ethanolamine, choline or serine in the phospholipid itself. The following diagram shows the structures of some of these components. Clicking on the diagram will change it to display structures for two representative phospholipids. Note that the fatty acid components (R & R ) may be saturated or unsaturated.
To see a model of a phospholipid .

As ionic amphiphiles, phospholipids aggregate or self-assemble when mixed with water, but in a different manner than the soaps and detergents. Because of the two pendant alkyl chains present in phospholipids and the unusual mixed charges in their head groups, micelle formation is unfavorable relative to a bilayer structure. If a phospholipid is smeared over a small hole in a thin piece of plastic immersed in water, a stable planar bilayer of phospholipid molecules is created at the hole. As shown in the following diagram, the polar head groups on the faces of the bilayer contact water, and the hydrophobic alkyl chains form a nonpolar interior. The phospholipid molecules can move about in their half the bilayer, but there is a significant energy barrier preventing migration to the other side of the bilayer.
This bilayer membrane structure is also found in aggregate structures called liposomes. Liposomes are microscopic vesicles consisting of an aqueous core enclosed in one or more phospholipid layers. They are formed when phospholipids are vigorously mixed with water. Unlike micelles, liposomes have both aqueous interiors and exteriors.
A cell may be considered a very complex liposome. The bilayer membrane that separates the interior of a cell from the surrounding fluids is largely composed of phospholipids, but it incorporates many other components, such as cholesterol, that contribute to its structural integrity. Protein channels that permit the transport of various kinds of chemical species in and out of the cell are also important components of cell membranes.
The interior of a cell contains a variety of structures (organelles) that conduct chemical operations vital to the cells existence. Molecules bonded to the surfaces of cells serve to identify specific cells and facilitate interaction with external chemical entities.
The sphingomyelins are also membrane lipids. They are the major component of the myelin sheath surrounding nerve fibers. Multiple Sclerosis is a devastating disease in which the myelin sheath is lost, causing eventual paralysis.

Steroids
The important class of lipids called steroids are actually metabolic derivatives of terpenes, but they are customarily treated as a separate group. Steroids may be recognized by their tetracyclic skeleton, consisting of three fused six-membered and one five-membered ring, as shown in the diagram to the right. The four rings are designated A, B, C & D as noted, and the peculiar numbering of the ring carbon atoms (shown in red) is the result of an earlier misassignment of the structure. The substituents designated by R are often alkyl groups, but may also have functionality. The R group at the A:B ring fusion is most commonly methyl or hydrogen, that at the C:D fusion is usually methyl. The substituent at C-17 varies considerably, and is usually larger than methyl if it is not a functional group. The most common locations of functional groups are C-3, C-4, C-7, C-11, C-12 & C-17. Ring A is sometimes aromatic. Since a number of tetracyclic triterpenes also have this tetracyclic structure, it cannot be considered a unique identifier.
Steroids are widely distributed in animals, where they are associated with a number of physiological processes. Examples of some important steroids are shown in the following diagram. Different kinds of steroids will be displayed by clicking the "Toggle Structures" button under the diagram. Norethindrone is a synthetic steroid, all the other examples occur naturally. A common strategy in pharmaceutical chemistry is to take a natural compound, having certain desired biological properties together with undesired side effects, and to modify its structure to enhance the desired characteristics and diminish the undesired. This is sometimes accomplished by trial and error.
The generic steroid structure drawn above has seven chiral stereocenters (carbons 5, 8, 9, 10, 13, 14 & 17), which means that it may have as many as 128 stereoisomers. With the exception of C-5, natural steroids generally have a single common configuration. This is shown in the last of the toggled displays, along with the preferred conformations of the rings.
Biosynthesis
The complex organic compounds found in living organisms on this planet originate from photosynthesis, an endothermic reductive condensation of carbon dioxide requiring light energy and the pigment chlorophyll.
x CO2 + x H2O + energy CxH2xOx + x O2

The products of photosynthesis are a class of compounds called carbohydrates, the most common and important of which is glucose (C6H12O6). Subsequent reactions effect an oxidative cleavage of glucose to pyruvic acid (CH3COCO2H), and this in turn is transformed to the two-carbon building block, acetate. The multitude of lipid structures are constructed from acetate by enzymatic reactions that in many respects correspond to reactions used by chemists for laboratory syntheses of similar compounds. However, an important restriction is that the reagents and conditions must be compatible with the aqueous medium, neutral pH and moderate temperatures found in living cells. Consequently, the condensation, alkylation, oxidation and reduction reactions that accomplish the biosynthesis of lipids
1.Condensations
2. Alkylations
3. An Alternative Isoprenoid Synthesis
Professor Dr. Saad Ali Ihsan
Ph.D. in Pharmacognosy & Medicinal Plants