NURS 207 (N01) Membrane Transport, September 12, 2024 PDF

NURS 207 (N01) Membrane transport Protein mediated and vesicular transport September 12, 2024 Dr. P. Lee  Objectives 1) Continue to descript the last two categories of transport processes Protein mediated transport Vesicular transport 2)...

NURS 207 (N01) Membrane transport Protein mediated and vesicular transport September 12, 2024 Dr. P. Lee  Objectives 1) Continue to descript the last two categories of transport processes Protein mediated transport Vesicular transport 2) Know the mechanisms of vesicular transport across the plasma membrane  4 main categories of transport processes → Bulk flow; diffusion; protein-mediated transport; and vesicular transport 3rd category of transport processes 3) Protein mediated transport 4 major groups of the membrane proteins and their respective physiological functions: Membrane proteins Membrane Structural Membrane Membrane transporters proteins enzymes receptors Transmembrane proteins 3) Protein mediated transport Majority of solutes transport across the membrane are in the form of protein mediated transport ✓ Because they are either lipophobic or electrically charged Non-polar lipophilic (lipid soluble) molecule can be dissolved in the central lipid region of the membrane and pass through it (such as lipids, steroids, and small lipophilic molecules) without involving protein mediated transport system Requires gradient (concentration, electrical or pressure) as the driving force When solute is moving through channels against the gradient, ATP (active transport) is required 3) Protein mediated transport With 2 sub-groups of transporters (channel transporters and carrier transporters): → Overlapping in both the structure and functions between these 2 sub-groups a) Channel transporters → Some channels with fluid filled chamber can have direct link between the intracellular and extracellular compartments → Allows very rapid transport across the membrane → Confined to the transport of smaller size ions and water 3) Protein mediated transport a) Channel transporters → Could have a cluster of tunnels or pores e.g. Water channel (aquaporin) with 4 sub-units i.e. 4 pores allowing water to pass through per aquaporin Crystallographic structure of the aquaporin 1 (AQP1) channel 3) Protein mediated transport a) Channel transporters → Can be divided into 2 types: ▪ Open channels or gated channels i) Open channels (leak channels) ✓ With pores open at all time and allow molecules moving in and out without restriction ✓ The only contributing factor for the direction of flow is the gradient http://www.biodiscover.com/image/microbe/1859.html 3) Protein mediated transport a) Channel transporters ii) Gated channels → Most of time in closed state → Movement of molecules occur only when the gate is opened Gated channels open and close in response to signals. Open Closed 3) Protein mediated transport a) Channel transporters ii) Gated channels Opening of gates can be regulated by: → Intracellular messenger molecules (second messenger system) → Or binding of ligand to the extracellular receptor (chemically gated channels) ✓ Ligand is the molecule that binds to the receptor → Changes the electrical state of the membrane (voltage-gated channels) → Stimulation to the membrane in the form pressure (mechanically gated channels) 3) Protein mediated transport Second sub-groups of transporters: b) Carrier transporters No direct contacts of the substrate between the intracellular and extracellular compartment at any given moment i.e. One end of the channel is always in a closing state Extracellular fluid Intracellular fluid Molecule Gate closed to be Carrier transported Membrane Gate closed 3) Protein mediated transport b) Carrier transporters → The transport of a substance across the channels is initiated by the binding of that substance (substrate/ligand) to the carrier proteins of the channels Extracellular fluid Intracellular fluid Molecule Gate closed to be Carrier transported Membrane Gate closed 3) Protein mediated transport b) Carrier transporters → It requires conformation changes to the carrier proteins (channels) in order to transport the substrate → Rate of transport is slower than the channel transporters, but can move larger molecules 3) Protein mediated transport MEMBRANE TRANSPORTERS b) Carrier transporters Carrier proteins never form an open channel between → Carrier transporters the two sides of the membrane. can be named according to the number of substrate Carrier open to ICF Same carrier open to ECF it carries as well as can be classified Cotransporters the direction of Uniport carriers substrates being transport only one kind of substrate. transported: Glu Na+ Glu Na+ → Uniport carriers ATP - move only one K+ kind of substrate ATP 3) Protein mediated transport MEMBRANE TRANSPORTERS b) Carrier transporters Carrier proteins never form an open channel between → Symport carriers the two sides of the membrane. - move more than one kind of Carrier open Same carrier substrates in the to ICF open to ECF can be classified same direction Cotransporters Symport carriers move two or more substrates in the same direction across the membrane. Glu Na+ Glu Na+ ATP K+ ATP 3) Protein mediated transport MEMBRANE TRANSPORTERS b) Carrier transporters Carrier proteins never form an open channel between the two sides of the membrane. → Antiport carriers - move more than one kind of Carrier open to ICF Same carrier open to ECF substrates in the can be classified opposite direction Cotransporters Antiport carriers move substrates in opposite directions. Glu Na+ Glu Na+ ATP K+ ATP  Summary of protein mediated transport across a membrane Channel Carrier transporter transporter Antiiport Uniport Symport Open channel Gated channel 3) Protein mediated transport 2 main categories of carrier proteins (based on the energy source that power the transport) a) Facilitated diffusion → Transported molecules move down their concentration gradient → Similar properties of transport as that of the simple diffusion → No energy is required for the transport process 3) Protein mediated transport 2 main categories of carrier proteins (based on the energy source that power the transport) b) Active transport → Transported molecules move against their concentration gradient → To create a state of disequilibrium by making the concentration gradient more pronounced → Require energy in the form of ATP to create a higher concentration gradient between the intracellular and the extracellular compartments  2 main categories of carrier proteins (based on the energy source that power the transport) b) Active transport → Active transport can be further divided into 2 types (primary & secondary active transport): → Both types of active transport require the binding of substrate to the carrier protein, leading to the conformation changes of the carrier proteins i) Primary (direct) active transport ✓ Require energy in the form of ATP to create a higher concentration gradient between the intracellular and the extracellular compartments  2 main categories of carrier proteins (based on the energy source that power the transport) b) Active transport i) Primary (direct) active transport ✓ These primary active transporters are also known as ATPase e.g.) Na+-K+-ATPase which transport 3 Na+ out of the cell and 2 K+ into the cell High in High in sodium potassium 140 ECF ICF Concentration (mmol/L) 120 100 80 60 40 20 Na+ Cl- K+ Na+ Cl- K+  2 main categories of carrier proteins (based on the energy source that power the transport) b) Active transport ii) Secondary (indirect) active transport These secondary active transporters use the potential energy created by the primary active transport and convert them into kinetic energy for the transport of substrate against the concentration gradient e.g.) Na+-glucose transporter (SGLT) → Na+ moving from high concentration to low → Glucose moving from low concentration to high  Na+ binds to carrier. Intracellular fluid Na+ Lumen of intestine Binding of to or kidney Na+ the receptor [Na+] high SGLT protein Glu [glucose] low [Na+] low [glucose] high Na+ binding creates Na+ a high-affinity site Followed by the for glucose. binding of glucose Glu to the receptor Lumen ICF Glucose binding changes carrier conformation so Na+ Conformational that binding sites now face the ICF. Closing of change to the carrier Lumenthe gate ICF Release of Na+ and glucose Na+ is released into cytosol, to the intracellular space where [Na+] is low. Release changes glucose-binding site to low affinity. Glucose Na+ (opening of the other gate) is released. [Na+] low [glucose] high Mechanism of the SGLT transporter Lumen ICF  Mechanisms of vesicular transport across the plasma membrane 4 main categories of transport processes → Bulk flow → Diffusion → Protein-mediated transport → Vesicular transport 4th category of transport processes 4) Vesicular transport For macromolecules that are too large for protein mediated transport (channel) systems to handle ATP is required for vesicular transport By means of: a) Endocytosis i.e. To internalize the macromolecules b) Exocytosis i.e. To release the macromolecules from intracellular to extracellular compartments 4) Vesicular transport a) Endocytosis 3 types: i) Receptor-mediated endocytosis ii) Phagocytosis iii) Pinocytosis a) Endocytosis i) Receptor-mediated endocytosis Receptor Also known as clathrin-mediated endocytosis Highly selective → require receptor Receptors for specific ligand (ligand is molecule that binds to specific receptor) are found on the extracellular surface of the membrane e.g.) LDL (low-density-lipoprotein) receptor mediated endocytosis of cholesterol–rich LDL) a) Endocytosis ii) Phagocytosis Involves engulfing large solid particles → Dead cells, damaged cells, bacteria, viruses, etc. By phagocytes → Such as macrophages (transformed from monocytes), and neutrophils Process begins when the particle binds to a plasma membrane receptor on the phagocyte a) Endocytosis Formation of pseudopods Binding to ii) Phagocytosis receptors Binding of particle to a plasma membrane receptor on the phagocyte is non-specific Surrounding and enclosing the macromolecule by the cell membrane to form a vesicle using pseudopods → This membrane-bound vesicle is known as phagosome a) Endocytosis iii) Pinocytosis Involves enclosing the extracellular fluid non-selectively → Also known as bulk-phase endocytosis → Droplets of extracellular fluid are taken up → No receptor proteins are involved → Digestion starts after fusion of vesicle and lysosome (containing digestion enzymes) → Processes commonly employed by the absorptive cells in the intestines and kidneys Pinocytosis enclosing of the extracellular fluid 4) Vesicular transport b) Exocytosis Process involve moving cytoplasmic vesicles to the plasma membrane → Fusing with the plasma membrane to form vesicle (secretory vesicle) → release the vesicle contents to the extracellular space Involves the release of digestive enzymes, hormones, mucus, and neural transmitters  ENERGY REQUIREMENTS MEMBRANE TRANSPORT Uses energy of Requires energy molecular motion. from ATP. Does not require ATP. Diffusion Endocytosis Secondary creates Primary Exocytosis Simple Facilitated active concentration active diffusion diffusion gradient Phagocytosis transport transport Molecule Mediated transport Uses a goes through requires a membrane-bound lipid bilayer. membrane protein. vesicle. PHYSICAL REQUIREMENTS Map of membrane transport  Sample questions 1) Which of the following transport process that requires cytoplasmic vesicle to fuse with the plasma membrane, following by the secretion of vesicular contents into the extracellular fluid? a) endocytosis b) exocytosis c) facilitated diffusion d) osmosis 2) Which of the following is NOT a true description of aquaporin? a) channel for water b) gated channel c) passive movement d) require chemical gradient  Sample questions 3) Which of the following vesicular transport process requires the binding of ligand to a highly selective receptor and subsequently initiates the clathrin-mediated endocytosis? a) Receptor-mediated endocytosis b) Phagocytosis c) Pinocytosis d) Exocytosis 4) Which of the following is best to describe the process that internalize macromolecules such as dead cells, damaged cells, bacteria, viruses, etc. through the plasma membrane? a) Endocytosis b) Phagocytosis c) Exocytosis d) Transcytosis  Sample questions 5) Majority of the electrolytes in intracellular fluid is composed of: a) Cl- b) Ca2+ c) Na+ d) K+ 6) Majority of the electrolytes in extracellular fluid is composed of: a) Cl- b) Ca2+ c) Na+ d) K+  Sample questions 7) In this type of transport process, a solute binds to a specific carrier protein on one side of the membrane. This binding induces a conformational change in the carrier protein that results in the other type of solute moving down its concentration gradient to the other side of the membrane. a) osmosis b) diffusion c) primary active transport d) facilitated diffusion 8) In this transport process, the energy from hydrolysis of ATP is used to drive substances across the membrane against their own concentration gradients. a) primary active transport b) facilitated diffusion c) secondary active transport d) osmosis  Answer to sample questions 1) b 2) b 3) a 4) b 5) d 6) c 7) d 8) a