Active Cell Mechanisms

Movements Through Cell Membranes

The cell membrane controls the substances that can enter and leave the cell. It does this by using passive and active mechanisms. Passive mechanisms do not require cellular energy, whereas active mechanisms do.

Active Cell Mechanisms

Particles sometimes move from a region of lower concentration to a region of higher concentration. When this occurs, energy is required. This energy comes from the cellular metabolism, specifically from the molecule known as ATP, which is created in the mitochondria of cells. Active cell mechanisms include active transport, endocytosis, and exocytosis.

Active Transport

Active transport is the movement of particlesthrough membranes from regions of lower concen-tration to regions of higher concentration. Similar to carrier-mediated facilitated diffusion, it also requires carrier proteins, which combine with transported substances both specifically and reversibly. This pro-cess is similar to facilitated diffusion because of its use of specific­ carrier molecules in the cell membranes (FIGURE 3 -15). These carrier molecules are proteins that have binding sites that combine with the parti-cles they are carrying. However, active transport dif-fers from facilitated diffusion in that ATP is required. Active ­transport moves sugar, amino acid, sodium, potassium, calcium, and hydrogen particles across cell membranes. Active transporters or solute pumps move solutes, mostly ions, against the concentration gradient, requiring energy. There are two types of active transport: primary and secondary.

Primary Active Transport

In primary active transport, required energy comes directly from the hydrolysis of ATP. Hydrolyzed ATP causes phosphorylation of the transport protein, chang-ing its shape so it pumps the bound solute across the membrane. Calcium and hydrogen pumps are primary active transport systems. However, perhaps the best studied of these systems is the sodium-potassium pump, which uses the enzyme sodium-potassium ATPase (Na⁺-K⁺ ATPase). Remember that the concentration of potassium inside cells is much higher than outside (by about 10 times), and the reverse is true of sodium. These balances are used for essential muscle and nerve cell function and to maintain normal fluid volume inall body cells. Sodium and potassium leak continu-ously yet slowly through leakage channels in the plasma membrane. They cross more quickly in stimulated mus-cle and nerve cells. Therefore, the sodium-potassium pump acts as a nearly continuous antiporter. It drives sodium out of cells, against a large concentration gradi-ent, as it pumps potassium back into them.

Ions driven by a concentration gradient may be slowed in their movement by the negative or positive charges of certain plasma membranes. Ions realisti-cally diffuse according to electrochemical gradients. Therefore, these gradients used by the sodium-­ potassium pump are the basis for most secondary active transport of ions as well as nutrients, of vital importance to cardiac, neuronal, and skeletal muscle function.

Secondary Active Transport

In the secondary active transport, the process indi-rectly uses energy that is stored in ionic gradients. These are created by primary active transport pumps. Second-ary active transport is a coupled system that moves more than one substance at a time. There are two subforms: in a symport system, the two substances are transported in the same direction, and in an antiport system, they cross the membrane in opposite directions.

One ATP-powered pump can indirectly drive the secondary active transport of a few other solutes. The pump stores energy in the ion gradient by mov-ing sodium against its concentration gradient, across the plasma membrane. A substance pumped across a membrane can accomplish work as it leaks back down along its concentration gradient. Therefore, other sub-stances are cotransported as sodium moves back into the cell via carrier proteins (a symport system). An example is the secondary active transport of certain sugars, amino acids, and ions into the cells that line the small intestine. Because the concentration gradient of the ion is used for energy, the ion has to be pumped out of the cell in order to maintain its diffusion gradient.

Antiport systems can also be driven by ion gradi-ents. An example of such an antiport system is one that helps regulate intracellular pH by using the sodium gradient for the expulsion of hydrogen ions. Each membrane pump or cotransporter transports only specific substances, no matter how energy is acquired to do so. When substances cannot pass by diffusion, the cell uses active transport systems to be selective. If there is no pump, nothing can be transported.

Vesicular Transport

Vesicular transport involves the transportation offluids with large particles and macromolecules across cellular membranes inside vesicles (membranous sacs). It is similar to active transport in that it also moves substances into and out of the cell. Vesicular transport is also used for transcytosis, in which substances are moved into, across, and out of cells. Vesicular traffick-ingis a process of movement of substances from anarea (or membranous organelle) to another. ATP is required for vesicular transport processes, but another compound (guanosine triphosphate) may also be used. For transcytosis and endocytosis, protein­-coated vesicles allow for movement of bulk solids, fluids, and most macromolecules.

Endocytosis

Endocytosis andexocytosisboth use energy from thecell to move substances into or out of the cell with-out crossing the cell membrane. Relatively large vol-umes of extracellular material are involved. Energy is required in the form of ATP. In endocytosis, a secre-tion from the cell membrane moves particles too large to enter the cell by other processes within a vesicle of the cell. Endosomes are endocytic vesicles. The three forms of endocytosis are phagocytosis, pinocytosis, and receptor-mediated endocytosis.

Phagocytosis

Phagocytosis (“cell eating”) involves cells takingin solids instead of liquids (FIGURE 3-16). Receptor-­ mediated endocytosis involves the movement of specific kinds of particles into the cell, with protein molecules extending through part of the cell mem-brane to the outer surface. This process is triggered when a particle­ binds to receptors on the cell’s sur-face. Pseudopods (cytoplasmic extensions) form and flow around the particle. A phagosome (endocytotic ­vesicle) is formed, which usually fuses with a lysosome as the contents are digested. Exocytosis is then used to eject any indigestible contents from the cell. The pri-mary cells used for phagocytosis are the macrophages and certain white blood cells, commonly referred to as phagocytes. These cells ingest and dispose of bacteria,other foreign substances, and dead tissue cells. Their disposal is important because dead cell remnants can trigger inflammation or stimulate an unwanted immune response. Phagocytes usually move via amoe-boid motion, with their cytoplasm flowing into tem-porary extensions that allow them to propel forward.

Pinocytosis

Pinocytosis (“cell drinking”) involves cells taking insmall liquid droplets from the surrounding cell envi-ronment with a small indentation of the cell membrane(FIGURE 3-16). It is also known as fluid-phase endo-cytosis. Infolding plasma membrane surrounds extra-cellular fluid that contains dissolved molecules. This small droplet enters the cell, fusing with an endosome. It is a routine activity of most cells, which differs from phagocytosis. Therefore, they can sample the extracel-lular fluid, which is an important ­function of cells that absorb nutrients such as those in the intestines. The parts of the plasma membrane that are removed during the internalization of the ­membranous sacs are recycled back via exocytosis. Therefore, the plasma membrane’s surface area can remain very constant. The endosomes that are formed by pinocytosis are called pinosomes.

Receptor-Mediated Endocytosis

Receptor-mediated endocytosis is the primary mech-anism for specific endocytosis and transcytosis of most macromolecules. Cells use it to focus just on material­ present in tiny amounts in the extracel-lular fluid. Plasma membrane proteins that bind ­specific ­substances are used. The receptors and their attached molecules are internalized in a pit coated with a bristled protein (clathrin). Then, pinocytosis or phagocytosis­ occurs. Most receptor molecules are glycoproteins, each binding to specific targets or ligands. Receptors bound to ligands usually clustertogether. Endosomes produced when groove or pock-ets form and move to one cellular area, and then pinch off, are called coated vesicles due to their surround-ing ­protein-fiber ­network. The coating is required to endosome formation and movement.

In the cell, the coated vesicles fuse with primary lysosomes containing digestive enzymes to create secondary lysosomes. Lysosomal enzymes free the ligands from the receptors. The ligands enter the cyto-plasm via active transport or diffusion. The vesicular membrane detaches and returns to the cell surface. Its receptors can then bind to more ligands.

Receptor-mediated endocytosis is used to take up enzymes, insulin and other hormones, iron, and low-density lipoproteins such as cholesterol. However, this process can be used to enter cells by cholera toxins, diphtheria, and the influenza virus. For other types of vesicular transport, coating proteins such as caveolae may be used. These are flask-shaped or tubular pockets of the plasma membrane. They capture certain mole-cules in coated vesicles and used forms of transcytosis.

Exocytosis

The opposite process to endocytosis is exocytosis, in which a substance stored in a vesicle is secreted from the cell (FIGURE 3-16). In exocytosis, stimulation occurs via binding of a hormone to a membrane receptor or because of a change in membrane voltage. Exocytosis is involved in hormone secretion, mucous secretion, neurotransmitter release, and sometimes waste ejection. A secretory vesicle forms, enclosing the substance to be removed from the cell. Usually, this vesicle migrates to and fuses with the plasma mem-brane. It then ruptures and its contents are spilled outside the cell. Exocytosis uses a process wherein transmembrane proteins (v-SNAREs) on the vesi-cles recognize specific plasma membrane proteins (t-SNAREs). They bind with them, causing the mem-branes to fuse together in a “corkscrew” pattern. Lipid monolayers are rearranged without mixing together with the transmembrane proteins. Material added by exocytosis is then removed by endocytosis.

1. Distinguish between phagocytosis and pinocytosis.

2. Explain the three active cell mechanisms.

3. Describe endocytosis.

4. Describe exocytosis.

5. Describe vesicular transport.