BIOCHEMISTRY - L. Stryer - 1984

VOLUME 1

PART I. CONFORMATION AND DYNAMICS

CHAPTER 10. AN INTRODUCTION TO BIOLOGICAL MEMBRANES

10.16. Membranes Are Asymmetric Structures

Membranes are asymmetric in both Structure and function, as exemplified by the orientation of Glycophorin and the anion channel, and, more generally, by the localization of CARBOHYDRATES on the outer surface of membranes. The outer and inner surfaces of all known Introduction/36.html">Biological Membranes differ in composition and enzymatic activity. A striking illustration of this is the pump that regulates Na⁺ and K⁺ concentrations in Cells. This transport system is present in the Plasma Membranes of almost all cells of higher organisms. The Na⁺-K⁺ pump is oriented in Cell/30.html">The Plasma Membrane in such a way that it pumps Na⁺ out of The Cell and K⁺ into the cell (Fig. 10.29). The pump also requires ATP, which must be on the inside of the membrane. Ouabain, a specific inhibitor of the pump, is effective only when applied from the outside of the membrane.

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Fig. 10.29. Asymmetry of the Na⁺-K⁺ coupled transport system in plasma membranes

As will be discussed in more detail in a later chapter (Section 29.32), the highly specific orientation of Membrane Proteins arises because they are synthesized and inserted into the membrane in an asymmetric manner. This absolute asymmetry is preserved because proteins do not undergo transmembrane movement during their lifetime in the membrane. Lipids are also asymmetrically distributed, which is due to The Mechanism of their Biosynthesis; however, except for Glycolipids, this asymmetry is rarely absolute. For example, in The erythrocyte membrane, sphingomyelin and phosphatidylcholine are located predominantly in the outer leaflet of the bilayer, whereas phosphatidylethanolamine and phosphatidylserine are located mainly in the inner leaflet. Cholesterol is abundant in both leaflets of the bilayer. The Functional Significance of lipid asymmetry is not yet clear.

10.17. Membrane Fluidity Is Controlled by Fatty Acid Composition and Cholesterol Content

In a membrane bilayer, the fatty acid chains of lipid molecules can exist in either a highly ordered, rigid state or a relatively disordered, fluid state. In the ordered state, all C—C bonds are in the trans conformation, whereas in the disordered state they are in the gauche conformation (Fig. 10.30). The transition from the solid (all-trans) to the fluid (partially gauche) state occurs as the Temperature is raised above the melting temperature, T_m. This transition temperature depends on the chain length and the degree of unsaturation of the acyl chains. Saturated acyl chains favor the rigid state because straight hydrocarbon chains can easily interact with one another (Fig. 10.31, A). In contrast, a cis double bond produces a bend in the hydrocarbon chain, which disrupts the highly ordered packing of the acyl chains, thereby lowering the T_m (Fig. 10.31, B). The transition temperature from the rigid to the fluid state also depends on chain length. Long hydrocarbon chains interact more strongly with one another than do short ones. Specifically, each additional —CH₂— group changes the Free energy of interaction between two adjacent hydrocarbon chains by about —0.5 kcal/mol.

Fig. 10.30. Conformation of C—C bonds in the hydrocarbon chains of fatty acid residues. A—trans (t) conformation. B and C—a 120° rotation yields the gauche (g) conformation, which can be g⁺ (clockwise rotation) or g^- (counterclockwise rotation). In the gauche conformation, the hydrocarbon chain bends at a 120° angle

Fig. 10.31. The presence of cis double bonds disrupts the highly ordered packing of fatty acid hydrocarbon chains. The space-filling models show the packing of: A—three stearate molecules (C₁₈, saturated), B—an oleate molecule (C₁₈, unsaturated) between two stearate molecules

Prokaryotes regulate the fluidity of their membranes by varying the number of double bonds and the length of their acyl chains. For example, The ratio of saturated to unsaturated fatty acid residues in the membrane of E. coli decreases from 1.6 to 1.0 when the growth temperature is lowered from 42 to 27°C. This decrease in the proportion of saturated Fatty acids prevents the membrane from becoming too rigid at lower temperatures. In eukaryotes, cholesterol is also a key regulator of membrane fluidity. By inserting between acyl chains, cholesterol prevents them from crystallizing. In essence, cholesterol abolishes the phase transition. On the other hand, cholesterol sterically hinders the extensive motion of acyl chains, thereby reducing membrane fluidity. Thus, due to these opposing effects of cholesterol, membrane fluidity is maintained at an intermediate level.