Lipids are water-insoluble components of cells that can be extracted by nonpolar solvents. Some lipids serve as structural components of membranes and others as storage forms of fuel. Fatty acids, which provide the hydrocarbon components of lipids, usually have an even number (12 to 24) of carbon atoms and may be saturated or unsaturated; unsaturated fatty acids have double bonds in the cis configuration. In most unsaturated fatty acids, one double bond is at the Δ9 position (between C-9 and C-10 ).
Triacylglycerols contain three fatty acid molecules esterified to the three hydroxyl groups of glycerol. Simple triacylglycerols contain only one type of fatty acid; mixed triacylglycerols contain at least two different types. Triacylglycerols are primarily storage fats; they are present in many types of foods.
The polar lipids, which have polar heads and nonpolar tails, are major components of membranes. The most abundant are the glycerophospholipids, which contain two fatty acid molecules esterified to two hydroxyl groups of glycerol, and a second alcohol, the head group, esterified to the third hydroxyl of glycerol via a phosphodiester bond. Glycerophospholipids differ in the structure of the head group; common glycerophospholipids are phosphatidylethanolamine and phosphatidylcholine. The polar heads of the glycerophospholipids carry electric charges at pH near 7. The sphingolipids, also membrane components, contain sphingosine, a long-chain aliphatic amino alcohol, but no glycerol. Sphingomyelin possesses, in addition to phosphoric acid and choline, two long hydrocarbon chains, one contributed by a fatty acid and the other by sphingosine. 1wo other classes of sphingolipids are neutral glycolipids and gangliosides, which contain various sugar components.
Cholesterol, a sterol, is a precursor of many steroids and is also an important component of plasma membranes of animal cells. All polar lipids are amphipathic; they have polar or charged heads and nonpolar hydrocarbon tails. They spontaneously form micelles, bilayers, and liposomes, stabilized by hydrophobic interactions.
Some types of lipids, although present in relatively small
quantities, play critical roles as cofactors or signals. Steroid
hormones are derived from sterols. Phosphatidylinositol is
hydrolyzed to yield two intracellular messengers, diacylglycerol
and inositol trisphosphate. Prostaglandins, thromboxanes, and
leukotrienes are extremely potent hormonelike molecules derived
from arachidonic acid. Vitamins A, D, E, and K are fat-soluble
compounds made up of isoprene units. All play essential roles in
the metabolism or physiology of animals. Vitamin A furnishes the
visual pigment of the vertebrate eye. Vitamin D is parent to a
hormone that regulates calcium and phosphate metabolism. Vitamin
E probably functions in the protection of membrane lipids from
oxidative damage, and vitamin K is essential in the
blood-clotting process. Ubiquinones and plastoquinones, also
isoprenoid derivatives, function as electron carriers in animals
and plants, respectively. Dolichols activate and anchor sugars on
cellular membranes for use in the synthesis of certain complex
carbohydrates and glycoproteins.
In the determination of lipid composition, lipids are extracted
from tissues with organic solvents and separated by thin-layer or
gas-liquid chromatography. Individual lipids are identified by
their chromatographic behavior, their susceptibility to
hydrolysis by specific enzymes, or by mass spectral determination
of their molecular masses.
General
Gurr, M.I. & Harwood, J.L. (1990) Lipid Biochemistry. An Introduction, 4th edn, Chapman & Hall, London.
A good general resource on lipid structure and metabolism, at the intermediate level.
Harwood, J.L. & Russell, N.J. (1984) Lipids in Plants and Microbes, George Allen & Unwin, Ltd., London.
Short, clear descriptions of lipid types, their distribution, metabolism, and function in plants and microbes; intermediate level.
Mead, J.F., Alfin-Slater, R.B., Howton, D.R., & Popjak, G. (1986) Lipids: Chemistry, Biochemistry and Nutrition, Plenum Press, New York.
An intermediate level textbook on chemical, metabolic, and nutritional aspects of lipids.
Vance, D.E. & Vance, J.E. (eds) (1991) Biochemistry of Lipids, Lipoproteins and Membranes, New Comprehensive Biochemistry, Vol. 20, Elsevier Science Publishing Co., Inc., New York.
An excellent collection of reviews on various aspects of lipid structure, biosynthesis, and funetion. Particularly germane are the chapters by K. Bloch (Cholesterol: evolution of structure and funetion); P.R. Cullis & M.J. Hope (Physical properties and funetional roles of lipids in membranes); C.C. Sweeley (Sphingolipids~; and W.L. Smith, P. Borgeat, & F.A. Fitzpatrick (The eicosanoids: cyclooxygenase, lipoxygenase, and epoxygenase pathways).
Structural Lipids in Membranes
Hakamori, S. (1986) Glycosphingolipids. Sci. Am. 254 (May), 44-53.
Ostro, M.J. (1987) Liposomes. Sci. Am. 256 (January), 102-111.
Sastry, P.S. (1985) Lipids of nervous tissue: composition and metabolism. Prog. Lipid Res. 24, 69176.
Spector, A.A. & Yorek, M.A. (1985) Membrane lipid composition and cellular function. J. Lipid Res. 26, 1015-1035.
Lipids with Specifcc Biological Activities Chojnacki, T. & Dallner, G. (1988) The biological role of dolichol. Biochem. J. 251, 1-9.
Fisher, S.K., Heacock, A.M., & Agranoff, B.W. (1992) Inositol lipids and signal transduction in the nervous system: an update. J. Neurochem. 58, 18-38.
A good discussion of the growing number of processes known to be controlled by metabolites of inositol-containing membrane lipids.
Machlin, L.J. & Bendich, A. (1987) Free radical tissue damage: protective role of antioxidant nutrients. FASEB J. 1, 441-445.
Brief discussion of tocopherols as antioxidants and their role in preventing damage by oxygen free radicals.
Shimizu, T. & Wolfe, L.S. (1990) Arachidonic acid cascade and signal transduction. J. Neurochem. 55, 1-15.
Role of arachidonie acid (20 : 4) as precursor to the eicosanoids.
Snyder, F., Lee, T.-C., & Blank, M.L. (1989) Platelet-activating factor and related ether lipid mediators: biological activities, metabolism, and regulation. Ann. N. Y. Acad. Sci. 568, 35-43.
Vermeer, C. (1990) γ-Carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase. Biochem. J. 266, 625-636.
Biochemical basis for the requirement of vitamin K in blood clotting, and the importance of carboxylation in the synthesis of the blood-clotting protein thrombin.
Viitala, J. & Jarnefelt, J. (1985) The red cell surface revisited. Trends Biochem. Sci. 10, 392-395. Includes discussion of the human A, B, and O blood type determinants.
Resolution and Analysis of Lipids
Kates, M. (1986) Techniques of Lipidology: Isolation, Analysis and Identification of Lipids, 2nd edn, Laboratory Techniques in Biochemistry and Molecular Biology, Vol. 3, Part 2 (Burdon, R.H. & van Knippenberg, P.H., eds), Elsevier Science Publishing Co., Inc., New York.
1. Melting Points of Fatty Acids The melting points of a series of 18-carbon fatty acids are stearic acid, 69.6 °C; oleic acid, 13.4 °C; linoleic acid, -5 °C; and linolenic acid, -11 °C. What structural aspect of these 18-carbon fatty acids can be correlated with the melting point? Provide a molecular explanation for the trend in melting points.
2. Spoilage of Cooking Fats Some fats used in cooking, such as olive oil, spoil rapidly upon exposure to air at room temperature, whereas others, such as solid shortening, remain unchanged. Why? 3. Preparation of Bearnaise Sauce During the preparation of bearnaise sauce, egg yolks are incorporated into melted butter to stabilize the sauce and avoid separation. The stabilizing agent in the egg yolks is lecithin (phosphatidylcholine). Suggest why this works.
4. Hydrolysis of Lipids Name the products of mild hydrolysis ol' the following lipids with dilute NaOH:
(a) 1-stearoyl-2,3-dipalmitoylglycerol
(b) 1-palmitoyl-2-oleoylphosphatidylcholine
5. Number of Detergent Mvlecules per Micelle When a small amount of sodium dodecyl sulfate (Na+CH3(CH2)11SO3- ) is dissolved in water, the detergent ions go into solution as monomeric species. As more detergent is added, a point is reached (the critical micelle concentration) at which the monomers associate to form micelles. The critical micelle concentration of SDS is 8.2 mM. An examination of the micelles shows that they have an average particle weight (the sum of the molecular weights of the constituent monomers) of 18,000. Calculate the number of detergent molecules in the average micelle.
6. Hydrophobic and Hydrophilic Components of Membrane Lipids A common structural feature of membrane lipid molecules is their amphipathic nature. For example, in phosphatidylcholine, the two fatty acid chains are hydrophobic and the phosphocholine head group is hydrophilic. For each of the following membrane lipids, name the components that serve as the hydrophobic and hydrophilic units:
(a) phosphatidylethanolamine
(b) sphingomyelin
(c) galactosylcerebroside
(d) ganglioside
(e) cholesterol
7. Properties of Lipids and Lipid Bilayers Lipid bilayers formed between two aqueous phases have this important property: they form two-dimensional sheets, the edges of which close upon each other, and undergo self sealing to form liposomes.
(a) What properties of lipids are responsible for this property of bilayers? Explain.
( b ) What are the biological consequences of this property with regard to the structure of biological membranes`?
8. Chromatographic Separation of Lipids A mixture of the following lipids is applied to a silica gel column, and the column is then washed with progressively more polar solvents. The mixture consists of: phosphatidylserine, cholesteryl palmitate (a sterol esterl, phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, palmitic acid, n-tetradecanol, triacylglycerol, and cholesterol. In what order do you expect the lipids to elute from the column?
9. Storage of Fat-Soluble Vitamins In contrast to water-soluble vitamins, which must be a part of our daily diet, fat-soluble vitamins can be stored in the body in amounts sufficient for many months. Suggest an explanation for this difference based on solubilities.
10. Alkali Lability of Triacylglycerols A common procedure for cleaning the grease trap in a sink is to add a product that contains sodium hydroxide. Explain why this works.
11. Dependence of Melting Point on Fatty Acid Unsaturation Draw all of the possible triacylglycerols that you could construct from glycerol, palmitic acid, and oleic acid. Rank them in order of inereasing melting point.
12. Operational Definition of Lipids How is the definition of "lipid" different from the definitions of other types of biomolecules that we have considered, such as amino acids, nucleic acids, and proteins?
13. Effect of Polarity on Solubility Rank, in order of increasing solubility in water, a triacylglycerol, a diacylglycerol, and a monoacylglycerol, all containing only palmitic acid.
l4.Intracellular Messengers from Phosphatidylinositols When the hormone vasopressin stimulates cleavage of phosphatidylinositol-4,5-bisphosphate by hormone-sensitive phospholipase C, two products are formed. Compare their properties and solubilities in water, and predict whether either would be expected to diffuse readily through the cytosol.
l5.Identification of Unknown Lipids Johann Thudichum, who practiced medicine in London about 100 years ago, also dabbled in lipid chemistry in his spare time. He isolated a variety of lipids from neural tissue, and characterized and named many of them. His carefully sealed and labeled vials of isolated lipids were rediscovered many years later. How would you confirm, using techniques available to you but not to him, that the vials he labeled "sphingomyelin" and "cerebroside" actually contain these compounds?
16. Analysis of Choline-Containing Phospholipids How would you distinguish sphingomyelin from phosphatidylcholine by chemical, physical, or enzymatic tests?
