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Chapter 3 Lecture Notes, page 1 Chapter 3 I. intercellular communication – extracellular chemical messengers (ligands) target cells have receptors specific for ligands when a ligand binds with its receptor, the physiological activity of target cell is altered signal transduction is the transfer of information from the ligand to the inside of the target cell A. signal transduction mechanisms 1. control of chemically-gated ion channels a. receptor binding site is part of channel channel opens when ligand binds with receptor, allowing ions to enter or leave the cell b. receptor binding site is in membrane near channel ligand binds with receptor in cell membrane, activating a G protein the G protein moves to the channel and opens or closes it in either case, the channel closes when the ligand is removed from its receptor the ions are moved back across the membrane, usually by ion pumps (active transport) 2. second messenger systems used when the ligand cannot enter the target cell a. general steps the ligand (called the first messenger) binds to its membrane receptor, activating a G protein the alpha subunit of the G protein activates a membrane effector protein, usually an enzyme the enzyme catalyzes the formation or activation of the intracellular second messenger b. the cAMP (cyclic AMP) second messenger mechanism BIOL 2305/Strong/Fall 2006 Chapter 3 Lecture Notes, page 2 the effector protein is the enzyme adenylyl cyclase, which converts intracellular ATP into cyclic AMP by removing 2 terminal phosphates cAMP activates the intracellular enzyme protein kinase A (PKA) PKA phosphorylates another enzyme, bringing about an enzyme cascade that produces the cellular response to the ligand cAMP is inactivated by phosphodiesterase (PDE) cAMP is used as a 2nd messenger in many different cell types – how can it generate different responses in different cells? What would happen if the first messenger inhibited adenylyl cyclase? c. amplification cascading amplifies the original signal from the first messenger one first messenger can lead to the activation of thousands of enzyme molecules and millions of product molecules inside the cell II. membrane transport A. whether or not something passes though a membrane depends on two things: 1. permeability of membrane permeable semi or selectively permeable impermeable What determines membrane permeability? a. the presence of the lipid bilayer b. the presence, size and selectivity of channels c. the presence of carrier proteins 2. permeating (penetrating) ability of molecule permeating/penetrating non-permeating/non-penetrating BIOL 2305/Strong/Fall 2006 Chapter 3 Lecture Notes, page 3 What determines molecule permeation? a. solubility in lipids electrical charge - uncharged molecules have greater lipid solubility polarity - nonpolar molecules have greater lipid solubility b. size - small molecules usually have greater permeating ability c. the presence of energy to move the molecule kinetic energy moves molecules down their concentration gradients in diffusion ATP, or metabolic energy, moves molecules in pumps and vesicular transport B. diffusion causes movement of a substance from an area where its concentration is higher to an area where its concentration is lower (down a concentration gradient) 1. physical basis molecules have kinetic (thermal) energy that causes them to move constantly and in random directions as the molecules move around they collide and bounce off each other given enough time they reach an even distribution the movement of more molecules in one direction than another is called net diffusion 2. factors that influence diffusion rate (# molecules per time) across a membrane a. concentration gradient b. membrane permeability c. surface area of membrane d. size of molecule e. distance the molecule has to diffuse BIOL 2305/Strong/Fall 2006 Chapter 3 Lecture Notes, page 4 3. electrical and electrochemical gradients ions have electrical charges; like charges repel each other opposite charges attract each other electrical gradients are due to an uneven distribution of electrical charges electrochemical gradients are due to an uneven distribution of charges and molecules 4. osmosis = diffusion of water through membranes water is moving down its concentration gradient water is moving away from the higher water concentration water is moving toward the higher solute concentration the solute is “pulling” the water to its side of the membrane a. penetrating vs nonpenetrating solutes if the solute can move through the membrane (penetrating), it will eventually become evenly distributed, osmosis will stop, the volumes on both sides of the membrane will be equal (osmosis only occurs until the solute has equilibrated across the membrane) if the solute cannot move through the membrane (nonpenetrating), it will continue to “pull” water towards it until water movement is stopped by the buildup of hydrostatic (fluid) pressure, then osmosis will stop and the volume on one side of the membrane will be larger than the volume on the other side b. osmotic pressure = the force that “pulls” water to the side of the membrane with the higher solute concentration the side of the membrane with the higher solute concentration has a higher osmotic pressure BIOL 2305/Strong/Fall 2006 Chapter 3 Lecture Notes, page 5 5. tonicity – refers to the effect of an extracellular solution on the volume of the cells it surrounds a. isotonic – ECF has same concentration of nonpenetrating solutes as ICF b. hypotonic – ECF has lower concentration of nonpenetrating solutes than ICF c. hypertonic – ECF has higher concentration of nonpenetrating solutes than ICF C. carrier-mediated transport molecules that cannot diffuse through the lipid bilayer or a channel may be transported by membrane carriers: the molecule attaches to a binding site on the carrier protein the carrier changes shape the molecule is released on the opposite side of the membrane 1. characteristics of membrane carriers a. specificity – each carrier has a specific 3-dimensional shape that allows only a certain shaped molecule to attach to it b. saturation – the number of molecules that can be transported at any given time depends on the number of carriers in the membrane c. competition – similarly-shaped molecules may compete for the carriers, decreasing the transport rate for the other molecules BIOL 2305/Strong/Fall 2006 Chapter 3 Lecture Notes, page 6 2. facilitated diffusion – moves molecules down their concentration gradient using kinetic energy (follows rules of both diffusion and carriers) a. the molecule binds to the carrier on the side of the membrane with the higher concentration b. when the molecule binds to the carrier it causes the carrier to change shape c. the molecule is released on the opposite side of the membrane 3. solute pumps – move molecules up or against their concentration gradient using ATP (follows rules of carriers) ATP provides energy to open the carrier on the low-concentration side of the membrane (phosphorylation) after the molecule binds, the carrier (pump protein) changes shape and simultaneously loses the phosphate group (dephosphorylation) after dephosphorylation, the carrier has lower affinity for the molecule and it is released on the high concentration side of the membrane a. primary active transport - the ATP that provides the energy is hydrolyzed by the primary transport carrier example: Na/K-ATPase (the sodium-potassium pump) phosphorylation (ATP) increases the carrier’s affinity for Na+ (inside the cell where the Na concentration is lower) 3 intracellular Na+ bind to carrier carrier changes shape and is simultaneously dephosphorylated dephosphorylation decreases carrier’s affinity for Na+ and increases affinity for K+ 3 Na+ are discharged into tissue fluid, 2 extracellular K+ bind to carrier (outside the cell where the K+ concentration is lower) carrier changes shape again and releases 2 K+ on inside of cell BIOL 2305/Strong/Fall 2006 Chapter 3 Lecture Notes, page 7 b. secondary active transport - the ATP works at one carrier to set up a concentration gradient for a molecule that will then be moved down its concentration gradient by a secondary carrier, usually taking another molecule up its gradient D. vesicular transport - used to move large polar molecules, droplets of fluid, or microbes across membranes 1. endocytosis cell membrane surrounds material to be transported and fuses to form a vesicle that encloses the material the vesicle separates from the membrane and can be moved around within the cell: o to combine with a lysosomes o to release material by exocytosis BIOL 2305/Strong/Fall 2006 Chapter 3 Lecture Notes, page 8 types of endocytosis: a. phagocytosis - used for bacteria and debris b. pinocytosis - used for engulfing fluid c. receptor-mediated endocytosis - occurs after material to be transported binds to receptors on cell surface 2. exocytosis vesicle inside cell fuses with cell membrane membrane opens to outside and releases material into ECF used to secrete cell products such as hormones and neurotransmitters used to add components to membrane III. membrane potential an uneven distribution of opposite electrical charges on the inside and outside of the cell membrane at rest, cell membranes are electrically polarized (negative inside/positive outside) energy has to be used to separate the charges to put them on opposite sides of the membrane because opposite charges attract each other, the force of that attraction can be used to do work a membrane potential is a form of potential energy potentials in cells are measured in millivolts (mV) a typical resting membrane potential is -70 mV A. role of Na/K pump 20% of the membrane potential due to the pump 3 Na+ pumped out for every 2 K+ pumped in leads to accumulation of + charges in the ECF anions cannot escape from the ICF to balance the electrical charges B. role of passive diffusion there are more K than Na passive leak channels in the membrane BIOL 2305/Strong/Fall 2006 Chapter 3 Lecture Notes, page 9 membrane is 50-75 times more permeable to K than to Na concentration gradients are established by the pump more K diffuses through the membrane than Na the Na/K pump maintains the difference BIOL 2305/Strong/Fall 2006