Transport Mechanisms Lecture Notes PDF

‫د رياض حنيوه‬ ‫جامعه وارث االنبياء‬ ‫كليه الطب‬ lecture 7 ‫قسم الكيمياء الحيوية والطبية‬ TRANSPORT MECHANISMS The permeability of substances across cell membrane is dependent on their solubility in lipids and not on their molecular size. Water soluble compounds are generally impermeable and req...

‫د رياض حنيوه‬ ‫جامعه وارث االنبياء‬ ‫كليه الطب‬ lecture 7 ‫قسم الكيمياء الحيوية والطبية‬ TRANSPORT MECHANISMS The permeability of substances across cell membrane is dependent on their solubility in lipids and not on their molecular size. Water soluble compounds are generally impermeable and require carrier mediated transport. An important function of the membrane is to withhold unwanted molecules, while permitting entry of molecules necessary for cellular metabolism. Transport mechanisms are classified into 1 ‫د رياض حنيوه‬ ‫جامعه وارث االنبياء‬ ‫كليه الطب‬ lecture 7 ‫قسم الكيمياء الحيوية والطبية‬ 1. Passive transport 1-A. Simple diffusion A. Simple Diffusion Solutes and gases enter into the cells passively. They are driven by the concentration gradient. The rate of entry is proportional to the solubility of that solute in the hydrophobic core of the membrane. Simple diffusion occurs from higher to lower concentration. This does not require any energy. However, it is a very slow process. 1-B. Facilitated diffusion. a. Facilitated diffusion can operate bidirectionally. 2 ‫د رياض حنيوه‬ ‫جامعه وارث االنبياء‬ ‫كليه الطب‬ lecture 7 ‫قسم الكيمياء الحيوية والطبية‬ b. This mechanism does not require energy but the rate of transport is more rapid than simple diffusion process. c. The carrier molecules can exist in two conformations, active sites are exposed to the exterior,when the solutes bind to the specific sites. Then there is a conformational change, the active sites are facing the interior of the cell, where the concentration of the solute is minimal. This will cause the release of the solute molecules . By this mechanism the inward flow is facilitated, but the outward flow is inhibited . Hormones regulate the number of carrier molecules. For example, glucose transport across membrane is by facilitated diffusion involving a family of glucose transporters. 3 ‫د رياض حنيوه‬ ‫جامعه وارث االنبياء‬ ‫كليه الطب‬ lecture 7 ‫قسم الكيمياء الحيوية والطبية‬ Aquaporins They are water channels . They are a family of membrane channel proteins that serve as selective pores through which water crosses the plasma membranes of cells. They form tetramers in the cell membrane, and facilitate the transport of water They control the water content of cells. Diseases such as nephrogenic diabetes insipidus is due to impaired function of these channels 4 ‫د رياض حنيوه‬ ‫جامعه وارث االنبياء‬ ‫كليه الطب‬ lecture 7 ‫قسم الكيمياء الحيوية والطبية‬ 1-C. Ion channels specialized carrier systems.They allow passage of molecules in accordance with the concentration gradient. Ion channels are trans- membrane proteins that allow the selective entry of various ions. These channels are for quick transport of electrolytes such as Ca++, K+, Na+ and Cl--. These are selective ion conductive pores. Ion channels are specialized protein molecules that span the membranes. The channels generally remain closed, but in response to stimulus, they open allowing rapid flux of ions down the gradient. Such ion channels are important for nerve impulse propagation, synaptic transmission and secretion of biologically active substances from the cells. Salient Features of Ion Channels 1. They are transmembrane proteins 2. Selective for one particular ion 3. Regulation of activity is done by voltage-gated, ligand-gated or mechanically gated mechanisms 4. Different channels are available for Na+, K+, Ca++ and Cl— 5. Transport through the channel is very quick 5 ‫د رياض حنيوه‬ ‫جامعه وارث االنبياء‬ ‫كليه الطب‬ lecture 7 ‫قسم الكيمياء الحيوية والطبية‬ 2. Active transport The salient features of active transport are: a. This form of transport requires energy. About 40% of the total energy expenditure in a cell is used for the active transport system b. The active transport is unidirectional. c. It requires specialized integral proteins called transporters. d. The transport system is saturated at higher concentrations of solutes. e. The transporters are susceptible to inhibition by specific organic or inorganic compounds. A. Sodium Pump It is the best example for active transport. Cell has low intracellular sodium; but concentration of potassium inside the cell is very high. This is maintained by the sodium–potassium activated ATPase, 6 ‫د رياض حنيوه‬ ‫جامعه وارث االنبياء‬ ‫كليه الطب‬ lecture 7 ‫قسم الكيمياء الحيوية والطبية‬ generally called as sodium pump. The ATPase is an integral protein of the membrane . It has binding sites for ATP and sodium on the inner side and the potassium binding site is located outside the membrane. It is made up of two pairs of unequal subunits α2 β2. B. Calcium Pump An ATP dependent calcium pump also functions to regulate muscle contraction. A specialized membrane system called sarcoplasmic reticulum is found in skeletal muscles which regulates the Ca++ concentration around muscle fibers. In resting muscle the concentration of Ca++ around muscle fibers is low. But stimulation by a nerve impulse results in a sudden release of large amounts of Ca++. This would trigger muscle contraction. The function of calcium pump is to remove cytosolic calcium and maintain low cytosolic concentration, so that muscle can receive the next signal. For each ATP hydrolysed, 2Ca++ ions are transported . uniport, symport and antiport systems Transport systems are classified as uniport, symport and antiport systems 1. Uniport system carries single solute across the membrane, e.g. glucose transporter in most of the cells. Calcium pump is another example. 2. If the transfer of one molecule depends on sequential transfer of another molecule, it is called co-transport system. The active transport may be coupled with energy indirectly. Here, movement of the substance against a concentration gradient is coupled with movement of a second substance down the concentration gradient; the second molecule being already concentrated within the cell by an energy requiring process. 7 ‫د رياض حنيوه‬ ‫جامعه وارث االنبياء‬ ‫كليه الطب‬ lecture 7 ‫قسم الكيمياء الحيوية والطبية‬ 3. The co-transport system may either be a symport or an antiport. In symport, the transporter carries two solutes in the same direction across the membrane, e.g. sodium dependent glucose transporter. 4. The antiport system carries two solutes or ions in opposite direction, e.g. sodium pump or chloride-bicarbonate exchange in RBC . END OF THE LECTUER Reference TEXTBOOK OF BIOCHEMISTRY Sixth Edition For Medical Students 8