Principles of Biochemistry Volume 1 - A. Lehninger 1985

Biomolecules
Lipids and Membranes
Chapter Summary

Lipids are fat-like, Water-insoluble cellular components that can be extracted by nonpolar Solvents. Some lipids serve as Structural components of membranes, while others act as a storage form of cellular «fuel». Fatty acids—the hydrophobic components of lipids—typically contain an even number of carbon atoms, most commonly 16 or 18. Fatty acids can be saturated or unsaturated, with the unsaturated ones existing in the cis-configuration. In most Unsaturated fatty acids, a single double bond is located at the ∆⁹-position. Sodium or potassium salts of Fatty acids are known as soaps. Triacylglycerol molecules contain three fatty acid molecules linked via ester bonds to the three hydroxyl groups of glycerol. Simple triacylglycerols contain fatty acids of only one type, whereas mixed triacylglycerols contain at least two different types. Triacylglycerols function primarily as the main storage form of fats in the Organism.

Polar lipids, consisting of polar HEAD groups and nonpolar hydrocarbon tails, are the principal components of Introduction/36.html">Biological Membranes. Among all polar lipids, phosphoglycerides are the most widespread. Phosphoglycerides contain two fatty acid molecules forming ester bonds with two free hydroxyl groups of glycerol-3-phosphate, and an additional alcohol molecule whose hydroxyl group is esterified with phosphoric acid. This alcohol residue constitutes the polar head of the entire phosphoglyceride molecule. Phosphoglycerides differ from one another in The Structure of their polar head groups. The most common phosphoglycerides are phosphatidylethanolamine and phosphatidylcholine. At pH values close to 7, the polar heads of phosphoglycerides carry a negative charge. In other Membrane Lipids, namely Sphingolipids, the structural backbone is not glycerol, but sphingosine. Such a sphingolipid as sphingomyelin contains, In addition to phosphoric acid and Choline, two long hydrocarbon chains: one formed by a fatty acid, and the second by sphingosine, a long-chain aliphatic amino alcohol. Cholesterol, which belongs to the sterols, acts as a precursor in The Biosynthesis of many Steroids and serves as an essential component of cellular Plasma Membranes.

All polar lipids contain polar or charged heads and nonpolar hydrocarbon tails; they spontaneously form micelles, monolayers, and bilayers stabilized by hydrophobic interactions. Polar lipid bilayers form the structural basis of Cell membranes, into which numerous Proteins are embedded—some (peripheral proteins) located On the surface, and others (integral proteins) spanning the interior of the membranes. The outer and inner surfaces of Membranes are asymmetric, with hydrophilic oligosaccharide groups of Glycoproteins and Glycolipids located exclusively on the outer surface. Some of these oligosaccharide groups play a crucial role in cell-Cell Recognition and adhesion, determine tissue Specificity, and constitute part of the receptor sites for Hormones.

References

Books

Ansell G.B., Hawthorne J.N., Dawson R.M. C. Form and Function of the Phospholipids, 2d ed., Elsevier, New York, 1973. A comprehensive Discussion of the subject.

Gurr A. L., James A. T. Lipid Biochemistry: An Introduction, 3d ed., Methuen, New York, 1980.

Hanson J.R. Introduction to Steroid Chemistry, Pergamon, New York, 1968. A concise summary of data.

Harrison R., Lunt G.G. Biological Membranes, Their Structure and function, 2d ed., Halsted, New York, 1980. An excellent, state-of-the-art book with numerous outstanding illustrations.

Weissmann G., Claiborne R. (eds.). Cell Membranes: Biochemistry, Cell Biology, and Pathology, H.P. Publishing Co., New York, 1975. An interesting and well-illustrated review.

Articles

Benson A. A., Lee R.F. The Role of Wax in Oceanic Food Chains, Sci. Am., 232, 77-86, March (1975).

Capaldi R.A. A Dynamic Model of Cell Membranes, Sci. Am., 230, 26-33, March (1974). An elaboration of the Singer-Nicolson model. Fishman P.N., Brady R. O. Biosynthesis and Function of Gangliosides, Science, 194, 90C 915 (1976).

Lodish H.F., Rothman J.E. The Assembly of Cell Membranes, Sci. Am., 240, 48-63, January (1979).

Lux S.E. Dissecting the Red Cell Membrane Skeleton, Nature, 281, 426-429 (1979).

Marchesi V. T. Spectrin: Present Status of a Putative Cyto-Skeletal Protein of the Red Cell Membrane, J. Membrane Biol., 51, 101 — 131 (1979).

Marx J.L. Liposomes: Research Applications Grow, Science, 199, 1056-1128 (1978).

Sharon N. Lectins, Sci. Am., 236, 108-119, June (1977).

Singer S.J., Nicolson G.L. The Fluid Mosaic Model of the Structure of Membranes, Science, 175, 720-731 (1972).

Questions and Problems

1. Melting points of fatty acids. Fatty acids with 18 carbon atoms have the following melting points: stearic acid +69.6°; oleic acid +13.4°C; linoleic acid -5°; and linolenic acid -11°C. What structural features determine the melting point of each of these acids? Explain the molecular basis underlying the observed trend in melting point variations.

2. Rancidity of culinary fats. Some cooking fats, such as butter, spoil rapidly when stored in air at room Temperature, whereas The properties of solid fats like margarine change very little under similar conditions. Why?

3. Preparation of mayonnaise. During the preparation of mayonnaise, phosphatidylcholine (lecithin) from egg yolks partitions into the vegetable oil, which stabilizes the emulsion and prevents it from separating. Explain why this happens.

4. Hydrolysis of lipids. Name the products formed upon mild hydrolysis of the following compounds with a dilute sodium hydroxide solution:

a) 1-stearoyl-2,3-dipalmitoylglycerol,

b) 1-palmitoyl-2-oleoylphosphatidylcholine.

What products are formed when substance b) is treated with hot concentrated NaOH?

5. Net electrical charge of phospholipids. What will be the charge at pH 7.0 of

a) phosphatidylcholine, b) phosphatidylethanolamine, and c) phosphatidylserine?

6. Protection in succulent plants. Succulents growing in arid regions are typically coated with a waxy layer.

How does this contribute to plant survival?

7. Number of detergent molecules in a micelle. When small amounts of sodium dodecyl sulfate

[CH₃(CH₂)₁₁ОSО₃Na⁺], a widely used detergent, are dissolved in water, the detergent ions remain in solution as monomers. As the detergent concentration increases, a point is reached (the critical micelle concentration) at which monomers associate to form micelles (Fig. 12-16). The critical micelle concentration for sodium dodecyl sulfate is 8.2 mM. Studies of micelle properties have shown that their average molecular mass is 18,000. Calculate how many detergent molecules are contained in a single micelle.

8. Hydrophobic and hydrophilic groups of membrane lipids. All membrane lipids are amphipathic compounds, meaning they contain both hydrophobic and hydrophilic groups. For example, in a phosphatidylcholine molecule, the hydrophobic portion consists of two fatty acid chains, and the hydrophilic portion is the phosphocholine head group. Name the structural components that act as hydrophobic and hydrophilic groups in each of the following membrane lipids:

a) phosphatidylethanolamine,

b) sphingomyelin,

c) galactocerebroside,

d) ganglioside,

e) cholesterol.

9. Properties of lipids and lipid bilayers. Lipid bilayers formed at the interface of two aqueous phases exhibit the following important properties: they form two-dimensional sheets; the edges of these sheets close in on themselves; and As a result of this self-sealing process, closed structures—liposomes—are formed.

a) Explain which lipid properties are responsible for these characteristics of bilayers.

b) What is the Biological Significance of these properties and how do they relate to the structure of biological membranes?

10. Permeation of ions across cell membranes. The Lipid Bilayer of The Cell membrane protects Cells from rapidly losing K⁺, Cl^-, and Mg²⁺ ions. Why?

11. Extraction of integral Membrane Proteins. Unlike cytoplasmic proteins, many membrane-embedded proteins are virtually impossible to Histology/2.html">EXTRACT FROM THE membrane into an aqueous solution (Fig. 12-17). Nevertheless, such Proteins can be successfully detached from the membrane and obtained in soluble form if sodium dodecyl sulfate (see Question 7) or another detergent, such as sodium cholate, is added to the extraction solution. What is the underlying principle of this technique?

12. Role of sugar residues in the orientation of membrane glycoproteins. Studies of various membrane glycoproteins show that sugar residues are always located on the outer surface of the membrane (see, for example, Fig. 12-18). One possible explanation for this phenomenon is that the sugar residues themselves ensure the asymmetric orientation of the glycoprotein within the membrane.

a) Why are sugar residues localized on the outer surface of the membrane rather than its interior?

b) Explain how sugar residues ensure the asymmetric distribution of glycoproteins in the membrane.

13. Membrane fluidity and its significance. According to the foundational hypothesis of membranology (the science of membranes), for membranes to function properly, their constituent lipids must be in a fluid (rather than "frozen") state. This hypothesis is supported by the observation that the fatty acid composition of bacterial membranes depends on their growth conditions. For instance, when Bacteria grow at lower temperatures, the relative proportion of unsaturated fatty acids increases (relative to saturated ones). Conversely, when bacteria grow at elevated temperatures, the level of unsaturated fatty acids (relative to saturated ones) is lower than normal.

a) Consider why membrane lipids must be in a fluid state for the normal functioning of an intact bacterial membrane.

b) Explain why the Observed changes in The ratio of saturated to unsaturated fatty acids depending on growth temperature support the hypothesis of membrane fluidity.