Like synthetic lipid bilayers, cell membranes allow small nonpolar molecules to permeate by diffusion. Cell membranes, however, also have to allow the passage of various polar molecules, such as ions, sugars, amino acids, nucleotides, water, and many cell metabolites that cross synthetic lipid bilayers only very slowly. Special membrane transport proteins transfer such solutes across cell membranes. These proteins occur in many forms and in all types of biological membranes. Each protein often transports only a specific molecular species or sometimes a class of molecules (such as ions, sugars, or amino acids). Studies in the 1950s found that bacteria with a single-gene mutation were unable to transport sugars across their plasma membrane, thereby demonstrating the specificity of membrane transport proteins. We now know that humans with similar mutations suffer from various inherited diseases that hinder the transport of a specific solute or solute class in the kidney, intestine, or other cell type. Individuals with the inherited disease cystinuria, for example, cannot transport certain amino acids (including cystine, the disulfide-linked dimer of cysteine) from either the urine or the intestine into the
Figure 11–1 The relative permeability of a synthetic lipid bilayer to different classes of molecules. The smaller the molecule and, more importantly, the less strongly it associates with water, the more rapidly the molecule diffuses across the bilayer.
Figure 11–2 Permeability coefficients for the passage of various molecules through synthetic lipid bilayers. The rate of flow of a solute across the bilayer is directly proportional to the difference in its concentration on the two sides of the membrane. Multiplying this concentration difference (in mol/cm3) by the permeability coefficient (in cm/sec) gives the flow of solute in moles per second per square centimeter of bilayer. A concentration difference of tryptophan of 10–4 mol/cm3 (10–4 mol / 10–3 L = 0.1 M), for example, would cause a flow of 10–4 mol/cm3 × 10–7 cm/sec = 10–11 mol/sec through 1 cm2 of bilayer, or 6 × 104 molecules/sec through 1 μm2 of bilayer.
blood; the resulting accumulation of cystine in the urine leads to the formation of cystine stones in the kidneys.
All membrane transport proteins that have been studied in detail are multi-pass transmembrane proteins—that is, their polypeptide chains traverse the lipid bilayer multiple times. By forming a protein-lined pathway across the membrane, these proteins enable specific hydrophilic solutes to cross the membrane without coming into direct contact with the hydrophobic interior of the lipid bilayer.
Transporters and channels are the two major classes of membrane transport proteins (Figure 11–3). Transporters (also called carriers, or permeases) bind the specific solute to be transported and undergo a series of conformational changes that alternately expose solute-binding sites on one side of the membrane and then on the other to transfer the solute across it. Channels, by contrast, interact with the solute to be transported much more weakly. They form continuous pores that extend across the lipid bilayer. When open, these pores allow specific solutes (such as inorganic ions of appropriate size and charge and in some cases small molecules, including water, glycerol, and ammonia) to pass through them and thereby cross the membrane. Not surprisingly, transport through channels occurs at a much faster rate than transport mediated by transporters. Although water can slowly diffuse across synthetic lipid bilayers, cells use dedicated channel proteins (called water channels, or aquaporins) that greatly increase the permeability of their membranes to water, as we discuss later.
Active Transport Is Mediated by Transporters Coupled to an Energy Source