Cell Membrane Transport PDF

Functional Systems of the Cell Transport of Substances through the Cell Membrane  The lipid bilayer is not miscible with either the extracellular fluid or the intracellular fluid. Therefore, it constitutes a barrier against movement of water molecules and water-soluble substances bet...

Functional Systems of the Cell Transport of Substances through the Cell Membrane  The lipid bilayer is not miscible with either the extracellular fluid or the intracellular fluid. Therefore, it constitutes a barrier against movement of water molecules and water-soluble substances between the extracellular and intracellular fluid compartment Diffusion diffusion means random molecular movement of substances molecule by molecule, either through intermolecular spaces in the membrane or in combination with a carrier protein. Active Transport active transport means movement of ions or other substances across the membrane in combination with a carrier protein in such a way that the carrier protein causes the substance to move against an energy gradient, such as from a low-concentration state to a high- concentration state. This movement requires an additional source of energy besides kinetic energy. Diffusion Diffusion through the cell membrane is divided into two subtypes called simple diffusion and facilitated diffusion. Simple diffusion means that kinetic movement of molecules or ions occurs through a membrane opening or through intermolecular spaces without any interaction with carrier proteins in the membrane. Facilitated diffusion requires interaction of a carrier protein. The carrier protein aids passage of the molecules or ions through the membrane by binding chemically with them. Aqueous diffusion: Aqueous diffusion is the movement of molecules through the watery extracellular and intracellular spaces. The membranes of most capillaries have small water-filled pores that permit the aqueous diffusion of molecules up to the size of small proteins between the blood and the extravascular space. This is a passive process governed by Fick's law Lipid diffusion Lipid diffusion is the movement of molecules through membranes and other lipid structures. For instance, the lipid solubilities of oxygen, nitrogen, carbon dioxide, and alcohols are high, so that all these can dissolve directly in the lipid bilayer and diffuse through the cell membrane in the same manner that diffusion of water solutes occurs in a watery solution. Like aqueous diffusion, this is a passive process governed by Fick's law Fick's law of diffusion: Fick's law predicts the rate of movement of molecules across a barrier The concentration gradient (C l - C2) and permeability coefficient for the drug and the area and thickness of the barrier membrane are used to compute the rate Rate can be calculated as follow: Rate = (C 1 - C2) x Permeability coefficient x Area / Thickness Carrier- mediated diffusion 1- Movement across the membrane is facilitated by a macromolecule. 2- An example of this mechanism is the uptake of glucose by cells. Properties: a) It is a saturable process. b) It is specific for the chemical structure of a drug. c) It requires no energy. d) It cannot move against a concentration gradient and therefore is still a diffusion process. Transport by special carriers: Drugs may be transported across barriers by mechanisms that carry similar endogenous substances, e.g. the amino acid carriers in the blood-brain barrier and the weak acid carriers in the renal tubule. Unlike aqueous and lipid diffusion, carrier transport is NOT governed by Fick's law and is capacity-limited. Transport by special carriers: Selective inhibitors for these carriers may have clinical value; e.g. probenecid, which inhibits transport of uric acid, and other weak acids, is used to increase the excretion of uric acid in gout. Probenecid is sometimes used along with penicillin antibiotics to increase antibiotic blood levels. This increase makes the antibiotic work better at treating certain infections. Probenecid works by decreasing the kidneys' ability to remove the antibiotic from the body. Facilitated Diffusion 1- Diffusion through protein channels 2- Channels move specific molecules across cell membrane 3- No energy needed Active transport It is similar to carrier-mediated diffusion in several ways: a) Movement across the membrane is mediated by a macromolecule. b) It is a saturable process. c) It is specific for chemical structure. Movement of Water across the cell Membrane Osmosis is diffusion of water from high concentration of water to low concentration of water across a semi-permeable membrane. Endocytosis If a cell is to live and grow and reproduce, it must obtain nutrients and other substances from the surrounding fluids. Most substances pass through the cell membrane by diffusion and active transport. Diffusion involves simple movement through the membrane caused by the random motion of the molecules of the substance; substances move either through cell membrane pores or, in the case of lipid soluble substances, through the lipid matrix of the membrane. Active transport involves the actual carrying of a substance through the membrane by a physical protein structure that penetrates all the way through the membrane. These active transport mechanisms are so important to cell functions.  Very large particles enter the cell by a specialized function of the cell membrane called endocytosis. The principal forms of endocytosis are pinocytosis and phagocytosis. Pinocytosis means ingestion of minute particles that form vesicles of extracellular fluid and particulate constituents inside the cell cytoplasm. Phagocytosis means ingestion of large particles, such as bacteria, whole cells, or portions of degenerating tissue. Endocytosis: Occurs through binding to receptors on cell membranes, with subsequent internalization by in-folding of that area of the membrane. The contents of the resulting vesicle are subsequently released into the cytoplasm of the cell. Permits very large or very lipid- insoluble chemicals to enter cells. e.g. peptides Smaller, polar substances such as vitamin Bl2 and iron combine with special proteins (B12 with intrinsic factor and iron with transferrin), and the complexes enter cells by Endocytosis. Pinocytosis Pinocytosis occurs continually in the cell membranes of most cells, but it is especially rapid in some cells. For instance, it occurs so rapidly in macrophages that about 3 per cent of the total macrophage membrane is engulfed in the form of vesicles each minute. Pinocytosis is the only means by which most large macromolecules, such as most protein molecules, can enter cells. Phagocytosis Phagocytosis occurs in much the same way as pinocytosis, except that it involves large particles rather than molecules. Only certain cells have the capability of phagocytosis, most notably the tissue macrophages and some of the white blood cells. Phagocytosis is initiated when a particle such as a bacterium, a dead cell, or tissue debris binds with receptors on the surface of the phagocyte.  In the case of bacteria, each bacterium usually is already attached to a specific antibody, and it is the antibody that attaches to the phagocyte receptors, dragging the bacterium along with it. This intermediation of antibodies is called opsonization.  Phagocytosis occurs in the following steps: 1. The cell membrane receptors attach to the surface ligands of the particle. 2. The edges of the membrane around the points of attachment evaginate outward within a fraction of a second to surround the entire particle; then, progressively more and more membrane receptors attach to the particle ligands. All this occurs suddenly in a zipper-like manner to form a closed phagocytic vesicle. 3. Actin and other contractile fibrils in the cytoplasm surround the phagocytic vesicle and contract around its outer edge, pushing the vesicle to the interior. 4. The contractile proteins then pinch the stem of the vesicle so completely that the vesicle separates from the cell membrane, leaving the vesicle in the cell interior in the same way that pinocytotic vesicles are formed. Lysosomes Function of the Lysosomes Almost immediately after a pinocytotic or phagocytic vesicle appears inside a cell, one or more lysosomes become attached to the vesicle and empty their acid hydrolases to the inside of the vesicle. Thus, a digestive vesicle is formed inside the cell cytoplasm in which the vesicular hydrolases begin hydrolyzing the proteins, carbohydrates, lipids, and other substances in the vesicle. The products of digestion are small molecules of amino acids, glucose, phosphates, and so forth that can diffuse through the membrane of the vesicle into the cytoplasm.  The lysosomes also contain bactericidal agents that can kill phagocytized bacteria before they can cause cellular damage. These agents include (1) lysozyme, which dissolves the bacterial cell membrane; (2) lysoferrin, which binds iron and other substances before they can promote bacterial growth; and (3) acid at a pH of about 5.0, which activates the hydrolases and inactivates bacterial metabolic systems. What is left of the digestive vesicle, called the residual body, represents indigestible substances. In most instances, this is finally excreted through the cell membrane by a process called exocytosis. Mitochondria Mitochondria oxygen and the foodstuffs—glucose, fatty acids, and amino acids—all entering the cell. Inside the cell, the foodstuffs react chemically with oxygen, under the influence of enzymes that control the reactions and channel the energy released in the proper direction. Briefly, almost all these oxidative reactions occur inside the mitochondria, and the energy that is released is used to form the high- energy compound ATP. Uses of ATP for Cellular Function Energy from ATP is used to promote three major categories of cellular functions: (1) transport of substances through multiple membranes in the cell (e.g. to supply energy for the transport of ions through the cell membrane). (2) synthesis of chemical compounds throughout the cell (e.g. to promote protein synthesis by the ribosomes). (3) mechanical work (to supply the energy needed during muscle contraction).