Transport Of Substances (2024) PDF

TRANSPORT OF SUBSTANCES ACROSS THE CELL MEMBRANE Prof.Dr.Mitat KOZ Chemical compositions of extracellular and intracellular fluids. One of the most important functions of the cell membrane is the regulation of material entry and exit into the cell. This is very important for the m...

TRANSPORT OF SUBSTANCES ACROSS THE CELL MEMBRANE Prof.Dr.Mitat KOZ Chemical compositions of extracellular and intracellular fluids. One of the most important functions of the cell membrane is the regulation of material entry and exit into the cell. This is very important for the maintenance of internal balance, that is, the continuity of homeostasis. One of the great wonders of the cell membrane is its ability to regulate the concentration of substances inside the cell  Membrane Permeability to Ions While the cell membrane is not permeable to negatively charged large molecules (cellular proteins, phosphate groups of ATP and other organic molecules) at rest, it is less permeable to Na+ ions and 25-75 times more permeable to K+ ions than Na+ ions. Cell membrane permeability to Cl- ions is higher than their permeability to Na and K ions. The permeability of the cell membrane to these ions is related to the number of ion channels open. The cell membrane has too many K leakage channels and fewer Na leakage channels.  The intracellular and extracellular distributions of ions There are differences between extracellular and intracellular fluids in terms of predominant solutes. The predominant solutes in the extracellular fluid The intracellular fluid contains are sodium and high concentrations of potassium chloride ions. ions and proteins with negatively charged side chains.  The intracellular and extracellular distributions of ions The intracellular and extracellular distributions of ions such as Na, K, Cl are different for three reasons: (1)The different permeability of the cell membrane to ions, (2)The presence of negatively charged large molecules that cannot pass through the cell membrane, and (3)the operation of the Na- K pump.  Gibbs-Donnan Equilibrium The Gibbs–Donnan effect (also known as the Donnan's effect, Donnan law, Donnan equilibrium, or Gibbs–Donnan equilibrium) is a name for the behaviour of charged particles near a semi-permeable membrane. The equilibrium state in which ions or molecules that cannot pass the cell membrane (proteins) are distributed by the passive movement of particles that can pass the membrane, according to their electrical charge. This behaviour of charged particles is called the Gibbs-Donnan Equilibrium. In such a state of equilibrium, the amounts of positive and negative charges on both sides of the cell membrane are equal. Cell Membrane Properties – Semi-Permeable Not just a container for the cell, plays a dynamic role in cellular activity The plasma membrane is a selectively permeable barrier. It only allows “selected” substances to pass through. Substances can pass though membrane by the passive or active transport mechanisms  Passive transport There are two main processes, – passive transport processes and – active transport processes. The main difference between the two is that passive processes do not require energy expenditure and active processes do require the cells to expend energy. The passive transport processes include – Diffusion simple diffusion, facilitated diffusion, – Osmosis – Fitration  concentration gradients and diffusion A concentration gradient is the difference in concentration of a substance across a space. Molecules (or ions) will spread or diffuse from where they are more concentrated to where they are less concentrated until they are equally distributed in that space. Diffusion is the movement of particles from an area of higher concentration to an area of lower concentration. Diffusion If a bottle of perfume were sprayed, the scent molecules would naturally diffuse from the spot where they left the bottle to all corners of the room, and this diffusion would go on until no more concentration gradient remains. Another example is a spoonful of sugar placed in a cup of tea. Eventually the sugar will diffuse throughout the tea until no concentration gradient remains. The rate of diffusion depends on what? Fick’s laws describe diffusion. One simplified arrangement states that ‘the rate of diffusion is proportional to the concentration gradient, the length of the diffusion pathway and the surface area available for diffusion‘. This can be written as follows:  Diffusion across the cell membrane is either “simple” or “facilitated” Simple diffusion occurs when molecules can move directly across the membrane without the aid of a carrier protein. Hydrophobic molecules such as O2 and CO2 diffuse readily in this way, as do small uncharged polar molecules such as urea. However, larger uncharged polar molecules, such as glucose, and charged molecules (ions), need carrier proteins to allow them to cross the lipid bilayer. This process is known as facilitated diffusion.  Oxygen (O2) and CO2 can easily diffuse through the lipid bilayer of the cell membrane. Simple Small uncharged polar molecules diffusion such as urea can diffuse via this way. O2 generally diffuses into cells because it is more concentrated outside of them, and CO2 typically diffuses out of cells because it is more concentrated inside of them. Neither of these examples requires any energy on the part of the cell, and therefore they use passive transport to move across the membrane.  Simple diffusion can occur through the cell membrane by two pathways: (1) through the small openings of the lipid bilayer if the diffusing substance is lipid soluble, and (2) through watery channels that penetrate all the way through some of the large transport proteins.  Diffusion of Lipid-Soluble Substances Through the Lipid Bilayer. One of the most important factors that determines how rapidly a substance diffuses through the lipid bilayer is the lipid solubility of the substance. 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. The rate of diffusion of each of these substances through the membrane is directly proportional to its lipid solubility.  Diffusion Through Protein Channels, and "Gating" of These Channels The protein channels on the cell membrane are distinguished by two important characteristics: (1) they are often selectively permeable to certain substances, and (2) many of the channels can be opened or closed by gates.  The opening and closing of gates are controlled in two principal ways: 1. Voltage gating. In this instance, the molecular conformation of the gate responds to the electrical potential across the cell membrane. When there is a strong negative charge on the inside of the cell membrane as in a resting cell, this would cause the outside Na gates to remain tightly closed;  The opening and closing of gates are controlled in two principal ways: 1. Voltage gating. when the inside of the membrane loses its negative charge as in the stimulated cell, these gates would open suddenly and allow tremendous quantities of sodium to pass inward The opening of these gates is through the sodium partly responsible for channels. depolarization phase the action potential.  The potassium gates are on the intracellular ends of the Voltage gating. potassium channels, and they open when the inside of the cell membrane becomes positively charged. – In resting the inside of the cell membrane is This is the basic negativeley charged. mechanism for eliciting The opening of these gates action potentials in nerves is partly responsible for that are responsible for repolarization phase of the nerve signals and muscle action potential. contractions.  The opening and closing of gates are controlled in two principal ways: 2. Chemical (ligand) gating. Some protein channel gates are opened by the binding of a chemical substance (a ligand) with the protein; this causes a conformational change in the protein molecule that opens or closes the gate. This is called chemical gating or ligand gating.  One of the most important examples of chemical gating is the effect of acetylcholine on the so- called acetylcholine channel. Acetylcholine opens the gate of this channel, providing a negatively charged pore. Opening of this channel allows uncharged molecules or positive ions to pass through. This gate is exceedingly important for the transmission of nerve signals from one nerve cell to another and from nerve cells to muscle cells to cause muscle contraction.  Facilitated diffusion Large polar or ionic molecules, which are hydrophilic, cannot easily cross the phospholipid bilayer. Very small polar molecules, such as water, can cross via simple diffusion due to their small size. But charged atoms or molecules of any size cannot cross the cell membrane via simple diffusion. Facilitated diffusion is the diffusion process used for those substances that cannot cross the lipid bilayer due to their size, charge, and/or polarity.  Facilitated diffusion A common example of facilitated diffusion is the movement of glucose into the cell. Although glucose can be more concentrated outside of a cell, it cannot cross the lipid bilayer via simple diffusion because it is both large and polar. To resolve this, a specialized carrier protein called the glucose transporter will transfer glucose molecules into the cell to facilitate its inward diffusion.  facilitated diffusion 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 and Among the most important shuttling them through substances that cross cell the membrane in this membranes by facilitated form. diffusion are glucose and most of the amino acids.  facilitated diffusion Exmp:Transport of glucose Glucose transporters(GLUT). There are 14 different subtypes – GLUT1-GLUT14 – In brain GLUT3 – In skeletal muscle, heart and adipose tissue GLUT4 Sensitive to insulin Insulin moves GLUT4 from cytoplasma to membrane  Water also can move Osmosis freely across the cell membrane of all cells, either through protein channels or by slipping between the phospholipid tails of the membrane itself. Osmosis is the diffusion of water through a semipermeable membrane  Osmosis is the Osmosis spontaneous net movement of solvent molecules through a selectively permeable membrane into a region of higher solute concentration  So it is important that cells are exposed to an environment in which the concentration of solutes outside of the cells (in the extracellular fluid) is equal to the concentration of solutes inside the cells (in the cytoplasm). If two solutions have the same concentration of solutes, It is said that they ara isotonic (equal tension). Body fluids are isotonic. When cells and their extracellular environments are isotonic, the concentration of water molecules is the same outside and inside the cells, and the cells maintain their normal shape (and function).  The human red blood cell (rbc) can serve as a living example of osmosis in the body. Their plasma membranes are permeable to water and certain solutes. Water can move in and out of rbc’s in response to changes in osmotic concentration of the fluid in which the red blood cells are suspended. Cells have a NaCl concentration equal to 0.9 %. Cells may be placed in test tube solutions that are equal to, greater than, or less than the NaCl concentration of the cell. Isotonic means that the cell’s environment has a NaCl concentration equal to the NaCl concentration that the cell has. In other words, the cell’s environment has a NaCl concentration equal to 0.9 %.  physiological saline or serum physiologic A sterile solution of sodium chloride that is isotonic to body fluids, used to maintain living tissue temporarily and as a solvent for parenterally administered drugs.  Lactated Ringer’s Solution (LR) Lactated Ringer’s solution, or simply “lactated Ringer’s” (LR), is one of two intravenous (IV) fluids that commonly used to restore hydration and fluid balance in the body. LR is an isotonic fluid, meaning that it has the same osmotic pressure, or weight, as blood. It is used for Fluid resuscitation, GI tract fluid losses, burns, traumas, or metabolic acidosis. It is often used during surgery. It is also used as an alkalinizing agent, which increases the pH level of the body.  5% Dextrose in Water (D5W) It starts as isotonic and then changes to hypotonic when dextrose is metabolized  Hypotonic means that the cell’s environment contains a lower concentration of NaCl than the cell itself has. In other words, the cell’s environment has a NaCl concentration less than 0.9%. 0.45% Sodium Chloride (0.45% NaCl) It is used to treat intracellular dehydration and hypernatremia and to provide fluid for renal excretion of solutes. If cells are placed in a hypotonic solution, there will be a net movement of water (osmosis) into the cell. The cells will swell and possibly burst -- bursting is described as hemolysis in red blood cells.  Hypertonic means that the cell’s environment contains a higher concentration of NaCl than the cell itself has. In other words, the cell’s environment has a NaCl concentration greater than 0.9 %. 3% Sodium Chloride (3% NaCl) 5% Dextrose and 0.45% Sodium Chloride (D5 0.45% NaCl) 5% Dextrose and Lactated Ringer’s (D5LR) They are used to treat severe hyponatremia and cerebral edema. If cells are placed in a hypertonic solution, there will be a net movement of water (osmosis) out of the cell which will cause the cell to shrink or crenate.  Filtration Filtration is the passage of materials through a membrane by a physical force such as hydrostatic pressure. In the body filtration is also achieved by means of a physical pump, the heart, which effects the rate of filtration by effecting the pressure of the blood through the blood vessels. – Capillary filtration in tissues. – Glomerular filtration in kidneys.  Capillary Exchange by filtration and Edema https://www.youtube.com/watch?v=6ecmOuCIoNc&t=4s&ab_channel=AlilaMedicalMedia  Passive transport There are two main processes, – passive transport processes and – active transport processes. The main difference between the two is that passive processes do not require energy expenditure and active processes do require the cells to expend energy. The passive transport processes include – Diffusion simple diffusion, facilitated diffusion, – Osmosis – Fitration  Active Transport For all of the transport methods described above, the cell expends no energy. During active transport, ATP is required to move a substance across a membrane, often with the help of protein carriers, and usually against its concentration gradient.  Active Transport Involves the expenditure of energy to move solutes across the cell membrane against their concentration gradient. Active transport can be primary or secondary. – In primary active transport, the direct hydrolysis of ATP provides the energy needed to transport the solute. – In secondary active transport, the movement of a molecule down its concentration gradient is coupled to the movement of a molecule up its concentration gradient. ATP is not directly involved.  Transport may be solo (uniport) or coupled Primary Active Transport (symport and antiport): 1. Uniport: – The hydrolysis of ATP “pumps” one molecule of one solute across a membrane against its gradient. – Lots of other examples. – Muscle cells contain Ca2+ uniporters. 2. Symport: – The hydrolysis of ATP pumps 2 molecules in the same direction against their concentration gradient  Primary Active Transport 3. Antiport: – Hydrolysis of ATP pumps one or more solute molecules against their gradient in one direction, and pumps one or more molecules against their gradient in the opposite direction. – Best example is the Na+/K+ pump which pumps 3 Na+ out of the cell and 2 K+ into the cell for each ATP hydrolyzed.  The sodium-potassium pump The sodium-potassium pump, which is also called Na+/K+ ATPase, transports sodium out of a cell while moving potassium into the cell. The Na+/K+ pump is an important ion pump found in the membranes of many types of cells. Between 60 and 70 per cent of a cell's energy consumption is consumed by ATP pumps. These pumps are particularly abundant in nerve cells, which are constantly pumping out sodium ions and pulling in potassium ions to maintain an electrical gradient across their cell membranes.  What is an electrical gradient across the cell membranes ? An electrical gradient is a difference in electrical charge across a membrane. In the case of nerve cells, for example, the electrical gradient exists between the inside and outside of the cell, with the inside being negatively-charged (at around -70 mV) relative to the outside. The negative electrical gradient is maintained because each Na+/K+ pump moves three Na+ ions out of the cell and two K+ ions into the cell for each ATP molecule that is used. This process is so important for nerve cells that it accounts for the majority of their ATP usage. Primary Active Transport of Calcium Ions Another important primary active transport mechanism is the calcium pump. Calcium ions are normally maintained at extremely low concentration in the intracellular cytosol of virtually all cells in the body, at a concentration about 10,000 times less than that in the extracellular fluid. This is achieved mainly by primary active transport. SERCA family of pumps, where SERCA stands for smooth endoplasmic reticulum Ca2+ ATPase, which is responsible for removing Ca2+ from the cytosol of a variety of cell types and placing it in storage in internal sacs within cells. Primary Active Transport of Hydrogen Ions At two places in the body, primary active transport of hydrogen ions is very important: – (1) in the gastric glands of the stomach – (2) in the late distal tubules and collecting ducts of the kidneys. In the gastric glands, the deep-lying parietal cells have the most potent primary active mechanism for transporting hydrogen ions Gastric H+-ATPase that is responsible for acidification of the stomach contents.  When a molecule is transported thruough the PM down its Secondary Active concentration gradient, energy Transport is released. This energy can be used to transport another molecule against its concentration gradient. This is secondary active transport. The best example is the transport of glucose in the digestive tract into the cells lining the small intestine. ATP is indirectly involved in this process. – ATP is spent to form the concentration gradient of ions such as Na. https://www.youtube.com/watch?v=oxX2fq2DBBo&t=14s&ab_channel=AlilaMedicalMedia  Big Stuff? Protein pumps are adequate for bring small molecules into the cell or out of the cell. However, a different kind of active transport is necessary to move large things into/out of the cell – vesicular transport. There are 2 types of vesicular transport: endocytosis and exocytosis  Exocytosis Exocytosis literally means “out of the cell” It accounts for hormone secretion, neurotransmitter release, mucus secretion, and, sometimes, ejection of wastes. – Inside the cell, the substance to be exported is enclosed in a membranous sac called a vesicle. – The vesicle will migrate to the PM fuse with it, and then rupture, spilling the contents into the extracellular space.  Endocytosis Reverse of exocytosis. Allows macromolecules to enter cells. – The substance is progressively enclosed by an enfolding portion of the plasma membrane. – This forms a vesicle which will pinch off the plasma membrane and enter the cytosol where it is typically digested. Types of endocytosis are: – Phagocytosis – Pinocytosis (a.k.a. bulk-phase endocytosis) – Receptor-mediated endocytosis  Literally “cell-eating.” Cytoplasmic extensions called Phagocytosis pseudopods “reach out and grab” large, solid material such as a clump of bacteria or cell debris, and then engulf it. The resulting vesicle is called a phagosome. Usually, the phagosome fuses with a lysosome, a membranous organelle that contains digestive enzymes, and its contents are digested. Macrophages and white blood cells are the most phagocytic cells in the body.  Pinocytosis Literally means “cell-drinking.” A bit of infolding plasma membrane surrounds a droplet of extracellular fluid containing dissolved molecules. This creates a tiny membranous vesicle. Most cells routinely perform this. Unlike phagocytosis, pinocytosis is unselective!  Receptor-Mediated Endocytosis Main mechanism for the specific uptake of macromolecules by most cells – remember, pinocytosis is non-selective and phagocytosis is typically only performed by macrophages and white blood cells. Molecules taken up by cells via RME include: – Enzymes – Hormones, e.g., insulin – Low-density lipoproteins (LDL), i.e., the “bad cholesterol” – Flu viruses and the diphtheria toxin also use RME to enter cells  Receptor-Mediated Endocytosis Receptors for the molecule to be ingested by a cell are on the PM. Different cells have different receptors and thus take up different molecules. A macromolecule will bind with its particular receptor and then these receptor-macromolecule complexes cluster together, invaginate and are internalized. https://www.youtube.com/watch?v=J5pWH1r3pgU&ab_channel=WhatsUpDude