13.1 The Transport of Molecules Across a Membrane May Be Active or Passive

For a net movement of molecules across a membrane, two features are required: (1) the molecule must be able to cross a hydrophobic barrier and (2) an energy source must power the movement. Lipophilic molecules can pass through a membrane’s hydrophobic interior by simple diffusion. These molecules will move down their concentration gradients. Polar or charged molecules require proteins to form passages through the hydrophobic barrier. Passive transport or facilitated diffusion takes place when an ion or polar molecule moves down its concentration gradient. If a molecule moves against a concentration gradient, an external energy source is required; this movement is referred to as active transport and results in the generation of concentration gradients. The electrochemical potential measures the combined ability of a concentration gradient and an uneven distribution of charge to drive species across a membrane.

392

13.2 Two Families of Membrane Proteins Use ATP Hydrolysis to Pump Ions and Molecules Across Membranes

Active transport is often carried out at the expense of ATP hydrolysis. P-type ATPases pump ions against a concentration gradient and become transiently phosphorylated on an aspartic acid residue in the process of transport. P-type ATPases, which include the sarcoplasmic reticulum Ca²⁺ ATPase and the Na⁺–K⁺ ATPase, are integral membrane proteins with conserved structures and catalytic mechanisms. Membrane proteins containing ATP-binding cassette domains are another family of ATP-dependent pumps. Each pump includes four major domains: two domains span the membrane and two others contain ABC P-loop ATPase structures. These pumps are not phosphorylated during pumping; rather, they use the energy of ATP binding and hydrolysis to drive conformational changes that result in the transport of specific substrates across membranes. The multidrug-resistance proteins confer resistance on cancer cells by pumping chemotherapeutic drugs out of a cancer cell before the drugs can exert their effects.

13.3 Lactose Permease is an Archetype of Secondary Transporters That Use One Concentration Gradient to Power the Formation of Another

Carriers are proteins that transport ions or molecules across the membrane without hydrolysis of ATP. They can be classified as uniporters, antiporters, and symporters. Uniporters transport a substrate in either direction, determined by the concentration gradient. Antiporters and symporters can mediate secondary active transport by coupling the uphill flow of one substrate to the downhill flow of another. Antiporters couple the downhill flow of one substrate in one direction to the uphill flow of another in the opposite direction. Symporters move both substrates in the same direction. Studies of the lactose permease from E. coli have been a source of insight into both the structures and the mechanisms of secondary transporters.

13.4 Specific Channels Can Rapidly Transport Ions Across Membranes

Ion channels allow the rapid movement of ions across the hydrophobic barrier of the membrane. The activity of individual ion-channel molecules can be observed by using patch-clamp techniques. Many ion channels have a common structural framework. In regard to K⁺ channels, hydrated potassium ions must transiently lose their coordinated water molecules as they move to the narrowest part of the channel, termed the selectivity filter. In the selectivity filter, peptide carbonyl groups coordinate the ions. Rapid ion flow through the selectivity filter is facilitated by ion–ion repulsion, with one ion pushing the next ion through the channel. Some ion channels are voltage gated: changes in membrane potential induce conformational changes that open these channels. Many channels spontaneously inactivate after having been open for a short period of time. In some cases, inactivation is due to the binding of a domain of the channel termed the “ball” in the mouth of the channel to block it. Other channels, typified by the acetylcholine receptor, are opened or closed by the binding of ligands. Ligand -gated and voltage-gated channels work in concert to generate action potentials. Inherited mutations or drugs that interfere with the ion channels that produce the action potential can result in potentially life threatening conditions.

393

13.5 Gap Junctions Allow Ions and Small Molecules to Flow Between Communicating Cells

In contrast with many channels, which connect the cell interior with the environment, gap junctions, or cell-to-cell channels, serve to connect the interiors of contiguous groups of cells. A cell-to-cell channel is composed of 12 molecules of connexin, which associate to form two 6-membered connexons.

13.6 Specific Channels Increase the Permeability of Some Membranes to Water

Some tissues contain proteins that increase the permeability of membranes to water. Each water-channel-forming protein, termed an aquaporin, consists of six membrane-spanning α helices and a central channel lined with hydrophilic residues that allow water molecules to pass in single file. Aquaporins do not transport protons.