Permeability of Biological Membranes

an important property of biological membranes that enables them to allow such metabolites as amino acids, sugars, and ions to enter and leave cells. The permeability of biological membranes has great importance in osmoregulation and in the maintenance of stability in the cell’s composition, that is, of the cell’s physico-chemical homeostasis. It is important in the generation and conduction of nervous impulses, in the provision of energy to the cell, and in other vital processes; it is also important in sensory mechanisms. The permeability of biological membranes results from the special structure of biological membranes, which serve as osmotic barriers between the cell and its environment. This permeability is an example of the unity and interrelationship of structure and function on the molecular level.

Biological membranes are permeable to only a small number of fat-soluble compounds of low molecular weight, such as glycerin, alcohols, and urea. Such permeability (simple diffusion) is relatively unimportant in processes for the transfer of substances across membranes. The more important transfer processes (translocations) occur with the aid of specific transport systems. It is believed that these systems contain membrane carriers (proteins or lipoproteins) and, possibly, a number of other components that fulfill functions related to transport, for example, the functions of receptors. The carrier or the carrier system bonds the substance being transported—the substrate—and can move within the membrane. If the carrier is immovably fixed within the biological membrane, pores or channels designated specifically for the compound being transported are believed to exist within the biological membrane (Figure 1).

Figure 1. Transport of a substance across a biological membrane with the aid of carriers: (S) substrate; (X), (Y), (a), (b), (c), (d), and (e) carriers; (A) transport with the aid of one carrier; (B) transport with the aid of two carriers; (C) transport through a specific channel (pore)

If the carrier bonds to the substrate by nonvalent interaction (ionic or hydrophobic), the process is called secondary translocation. There are three types of secondary translocation (Figure 2): facilitated diffusion (uniport), cotransport (symport), and countertransport (antiport). The mechanism of facilitated

Figure 2. Mechanism of secondary translocation: (S) and (R) substrates, (X) carrier, (A) uniport, (B) symport, (C) antiport

diffusion does not depend on the transfer of other substances into or out of the cell. For example, glucose is transferred into red blood cells by this means.

Cotransport is the combined transport of two or more substances in one direction. Thus, the transport of glucose and amino acids across the mucous membrane of the small intestine is linked to the transport of Na⁺ ions. The mechanism of countertransport entails the linking of the transfer of a substance in one direction with the movement of another substance in the opposite direction. The transfer in opposite directions of Na⁺ and K⁺ ions in nerve cells occurs in this way.

Processes of linked transport (symport and antiport) have great importance when the substance being transferred moves against a density gradient (from a region of lesser to a region of greater concentration). Such active transport, differing from passive transport in terms of the density gradient, requires expenditure of energy. This energy is obtained from the linking of secondary translocation with enzymatic reactions involving disruption or formation of chemical bonds. In addition, the energy of the chemical transformation is expended on maintaining the osmotic potential or the asymmetry on both sides of the membrane.

The transport of substances across biological membranes that is related to the disruption or formation of chemical bonds is called primary translocation. A typical example is the operation of the sodium pump combined with the hydrolysis of the energy-rich compound adenosine triphosphate (ATP) catalyzed by the enzyme adenosine triphosphatase. The hydrolysis of ATP is accompanied by the transfer of Na⁺ ions from within the cell and by the entry of K⁺ ions into the cell. It is believed that the K⁺ ion carrier is the free enzyme, while the carrier of Na⁺ ions is the phosphorylated enzyme formed in the hydrolysis of ATP.

Carriers have not yet been isolated from the biological membranes of the cells of animals. The existence of carriers (called permeases) has been clearly demonstrated in bacteria, chiefly by genetic methods. Some permeases have been isolated in pure form, for example, M protein, the carrier of lactose in Escherichia coli. There are indications that the active transport of sugars and amino acids in bacteria is coupled with the oxidation of D-lactic acid. In some bacteria, a great many bonding proteins have been observed; these proteins may be the receptor components of the corresponding transport systems.

The permeability of biological membranes is regulated by hormones and other biologically active substances. Thus, insulin and some steroid hormones increase the permeability of the membranes of red blood, muscle, and adipose cells. The permeability of the membranes of such excitable cells as nerve cells depends on special substances called mediators (for example, acetylcholine). Permeability for ions is strongly affected by the antibiotics valinomycin, gramicydin, and nonactin, as well as by some synthetic polyesters. In studies on the permeability of biological membranes, which is one of the outstanding problems in molecular biology, of great importance are modeled membranes: lipid monolayers, artificial two-layer membranes, and multilayer closed membranes (liposomes). Electrochemical, physical, and chemical methods are widely used in studying the permeability of biological membranes.