Lipids

Page 1143
aminic acid, a sialic acid, is
Lipids
Lipids are a diverse group of chemicals related primarily because they are insoluble in water, soluble in nonpolar solvents, and found in animal and plant tissues.
Saponifiable lipids yield salts of fatty acids upon alkaline hydrolysis. Acylglycerols = glycerol + fatty acid(s); phosphoacylglycerols = glycerol + fatty acids + HPO42–
+ alcohol; sphingolipids = sphingosine + fatty acid + polar group (phosphorylalcohol or carbohydrate); waxes = long­chain alcohol + fatty acid. Nonsaponifiable lipids (terpenes, steroids, prostaglandins, and related compounds) are not usually subject to hydrolysis. Ampbipathic lipids have both a polar ''head" group and a nonpolar "tail." Amphipathic molecules can stabilize emulsions and are responsible for the lipid bilayer structure of membranes.
Fatty acids are monocarboxylic acids with a short (<6 carbon atoms), medium (8–14 carbon atoms), or long (>14 carbon atoms) aliphatic chain. Biologically important ones are usually linear molecules with an even number of carbon atoms (16–20). Fatty acids are numbered using either arabic numbers (COOH is 1) or the Greek alphabet (COOH is not given a symbol; adjacent carbon atoms are a , b , g, etc.). Saturated fatty acids have the general formula CH3CH2)nCOOH. (Palmitic acid = C16; stearic acid = C18.) They tend to be extended chains and solid at room temperature unless the chain is short. Both trivial and systematic (prefix indicating number of carbon atoms + anoic acid) names are used. CH3(CH2)14COOH = palmitic acid or hexadecanoic acid.
Unsaturated fatty acids have one or more double bonds. Most naturally occurring fatty acids have cis double bonds and are usually liquid at room temperature. Fatty acids with trans double bonds tend to have higher melting points. A double bond is indicated by n, where n is the number of the first carbon of the bond. Palmitoleic = 9­hexadecenoic acid; oleic = 9­octadecenoic acid; linoleic = 9,12­octadecadienoic acid; linolenic = 9,12,15­octadecatrienoic acid; arachidonic = 5,8,11,14­eicosatetraenoic acid. Since fatty acids are elongated in vivo from the carboxyl end, biochemists use alternate terminology to assign these fatty acids to families: omega ( ) minus x (or n – x), where x is the number of carbon atoms from the methyl end where a double bond is first encountered. Palmitoleic is an – 7 and oleic is an – 9 acid, linoleic and arachidonic are – 6 acids, and linolenic is an – 3 acid. Addition of carbon atoms does not change the family to which an unsaturated fatty acid belongs.
Since the pK values of fatty acids are about 4–5, in physiological solutions, they exist primarily in the ionized form, called salts or "soaps." Long­chain fatty acids are insoluble in water, but soaps form micelles. Fatty acids form esters with alcohols and thioesters with CoA.
The following are biochemically significant reactions of unsaturated fatty acids:
1. Reduction
2. Addition of water
3. Oxidation
Prostaglandins, thromboxanes, and leukotrienes are derivatives of C20, polyunsaturated fatty acids, especially arachidonic acid. Prostaglandins have the general structure:
The series differ from each other in the substituents on the ring and whether C­15 contains an OH or O . OH group. The subscript indicates the number of double bonds in the side chains. Substituents indicated by –(b ) are above the plane of the ring; . . . (a ) below:
Page 1144
Thromboxanes have an oxygen incorporated to form a six­membered ring:
Leukotrienes are substituted derivatives of arachidonic acid in which no internal ring has formed; R is variable:
Acylglycerols are compounds in which one or more of the three OH groups of glycerol are esterified. In triacylglycerols (triglycerides) all three OH groups are esterified to fatty acids. At least two of the three R groups are usually different. If R1 is not equal to R3, the molecule is asymmetric and of the L configuration:
The properties of the triacylglycerols are determined by those of the fatty acids they contain, with oils being liquid at room temperature (preponderance of short­chain and/or cis­unsaturated fatty acids) and fats being solid (preponderance of long­chain, saturated, and/or trans­unsaturated).
Triacylglycerols are hydrophobic and do not form stable micelles. They may be hydrolyzed to glycerol and three fatty acids by strong alkali or enzymes (lipases). Mono­ [usually with the fatty acid in the b (2) position] and diacylglycerols also exist in small amounts as metabolic intermediates. Mono­ and diacylglycerols are slightly more polar than triacylglycerols. Phosphoacylglycerols are derivatives of L­ a ­glycerolphosphate (L­glycerol 3­phosphate):
The parent compound, phosphatidic acid (two OH groups of L­ a ­glycerolphosphate esterified to fatty acids), has its phosphate esterified to an alcohol (XOH) to form several series of phosphoacylglycerols. These are amphipathic molecules, but the net charge at pH 7.4 depends on the nature of X–OH.
X—OH
Phosphoacylglycerol
Phosphatidylcholines (lecithins)
Phosphatidylethanolamines (cephalins)
Phosphatidylserines
Phosphatidylinositols phosphate on 4, or 4 and 5
In plasmalogens, the OH on C­1 is in ether, rather than ester, linkage to an alkyl group. If one fatty acid (usually b ) has been hydrolyzed from a phosphoacylglycerol, the compound is a lyso­compound; for example, lyso­phosphatidylcholine (lysolecithin):
Sphingolipids are complex lipids based on the C­18, unsaturated alcohol, sphingosine. In ceramides, a long­chain fatty acid is in amide linkage to sphingosine:
Sphingomyelins, the most common Sphingolipids, are a family of compounds in which the primary OH group of a ceramide is esterified to phosphorylcholine (phosphorylethanolamine):
Page 1145
They are amphipathic molecules, existing as zwitterions at pH 7.4 and the only sphingolipids that contain phosphorus. Glycosphingolipids do not contain phosphorus but contain carbohydrate in glycosidic linkage to the primary alcohol of a ceramide. They are amphipathic and either neutral or acidic if the carbohydrate moiety contains an acidic group. Cerebrosides have a single glucose or galactose linked to a ceramide. Sulfatides are galactosylceramides esterified with sulfate at C­3 of the galactose:
Globosides (ceramide oligosaccharides) are ceramides with two or more neutral monosaccharides, whereas ganglio­sides are an oligosaccharide containing one or more sialic acids.
Steroids are derivatives of cyclopentanoperhydrophe­nanthrene. The steroid nucleus is a rather rigid, essentially planar structure with substituents above or in the plane of the rings designated b (solid line) and those below called a (dotted line):
Most steroids in humans have methyl groups at positions 10 and 13 and frequently a side chain at position 17. Sterols contain one or more OH groups, free or esterified to a fatty acid. Most steroids are nonpolar. In a liposome or cell membrane, cholesterol orients with the OH toward any polar groups; cholesterol esters do not. Bile acids (e.g., cholic acid) have a polar side chain and so are amphipathic:
Steroid hormones are oxygenated steroids of 18–21 carbon atoms. Estrogens have 18 carbon atoms, an aromatic ring A, and no methyl at C­10. Androgens have 19 carbon atoms and no side chain at C­17. Glucocorticoids and mineralocorticoids have 21 carbon atoms, including a C2, of oxygenated side chain at C­17. Vitamin D3 (cholecalciferol) is not a sterol but is derived from 7­dehydrocholesterol in humans:
Terpenes are polymers of two or more isoprene units. Isoprene is
Terpenes may be linear or cyclic, with the isoprenes usually linked head to tail and most double bonds trans (but may be cis as in vitamin A). Squalene, the precursor of cholesterol, is a linear terpene of six isoprene units. Fat­soluble vitamins (A, D, E, and K) contain isoprene units: