Membrane Transport

Membrane Transport - Ch Chapter 20 20 Transport through...

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

Unformatted text preview: Ch Chapter 20 20 Transport through membrane through membrane Why do we need transport? • To import biological molecules (fuel and building blocks) blocks) • To export wastes • Transport of building blocks or degradation of building blocks or degradation products between organelles and the cytosol • Regulate the osmotic pressure the osmotic pressure • Regulate the concentration of certain ions • Create gradients of ions across membranes gradients of ions across membranes Transport across membranes is usually mediated by proteins • Membranes have a hydrophobic core • Small non-polar substances are able to pass through membranes unassisted • The passage of polar or charged molecules is mediated by proteins Movement of solutes across a permeable membrane Electrically neutral solutes Electrically charged solutes Thermodynamics of the neutral species transport A (out) A (in) ΔG A = G A (in) − G A (out) ΔGA = G°A + RT ln[A ]in - (G°A + RT ln[A ]out ) [A]in ΔGA = RTln [A]out Thermodynamics of the ionic species transport ΔGA = • • • • [A]in RTln + ZAF ΔΨ [A]out R = gas constant 8.314 J/°K.mol gas constant J/ ZA = ionic charge of A F = 96485 C/mol 96485 C/mol ΔΨ = Ψin-Ψout membrane potential V 1V = 1 J/C Types of transport • Non-mediated transport (Diffusion) • Mediated transport (Specific carrier proteins) transport (Specific carrier proteins) – Passive-mediated transport or facilitated diffusion: From high to low concentration From high to low concentration – Active transport: From low to high concentration; Requires energy (ATP) Transport types Kinetics of non-mediated diffusion Rate of diffusion across a membrane correlates with concentration gradient with a concentration gradient JA = PA([A]out-[A]in) Permeability correlates with membrane solubility Transporters lower the energy barrier Passive transport • Carriers: Valinomycin • Channels or pores: Gramicidin A, Porins, Ion Channels • Transport proteins: Erythrocyte glucose transporter (GLUT1) Ionophores Valinomycin carries K+ across the membrane Monensin is the Na+-binding ionophore Gramicidine A forms helical transmembrane channels 4Å H+, Na+ and K+ Head-to-head dimer forms a β helical channel Porins Aquaporins • Rapid water transport (~3x109 per sec) • Highly selective to water (not even H3O+) selective to water (not even • Widely distributed in bacteria, plants and animals animals • Highly expressed in tissues such as kidneys, salivary glands and lacrimal glands salivary glands, and lacrimal glands Structure of aquaporin Water transport channel Both size and charge matter for the selectivity K+ channels • Facilitate the diffusion of K+ from the cytoplasm ([K+]>100 mM) to the extracellular space ([K+]< 5 mM) • Important for cellular osmotic balance, neurotransmission, and signal transduction • Highly selective to K+ ion; 10000-fold over Na+ ion • 108 ions/sec • KcsA is a tetramer; each subunit forms two helices; four subunits assemble to form a central pore • Narrow upper part of the pore (3 Å), wide central part (10 Å) and narrow cytoplasmic side (6 Å) • K+ ion must be dehydrated at the top to fit into the top part (selectivity filter) • An array of carbonyl oxygens stabilize K+ ion at the upper part K+ channel Function of K+ channel Cl- channels [Cl-]Out = ~ 120 mM [Cl-]in = ~ 4 mM Basic amino acids form a selective funnel for anions Evidence of a selective system for the glucose transport Kinetics of glucose transport into erythrocytes (a (a mediated transport) J max [A] JA = K M + [A] Proposed structure of GLUT1 “Gated pore” model for glucose transporter Glucose transporters in the human genome Insulin stimulates the glucose uptake in muscle and fat cells ce Stoichiometry of the transport systems Active transport • Transport ions and neutral molecules against the concentration gradient against the concentration gradient • Often coupled to the hydrolysis of ATP (ATPase activity) (ATPase activity) Four types of ATPases • Cation transporters – P-type ATPases • • • • Located in plasma membranes Autophosphorylation by ATP Transport H+, Na+, K+, Ca2+, Cu2+, Cd2+ and Mg2+ Inhibited by vanadate (VO43-) (VO – F-type ATPases • Translocate H+ into mitochondria and bacterial cells • Power ATP synthesis ATP synthesis – V-type ATPase • Located in plant vacuolar membranes and acidic vesicles • Homologous to F-type ATPases to ATPases • Anionic transporters – A-type ATPses Two types of active transport Na+K+ ATPase • Regulation of osmotic pressure • Maintaining membrane potential • Maintaining sodium and potassium gradients Putative structure of Na+K+ ATPase The Na+K+ ATPase pumps 3 Na+ ions out and 2 K+ ions in Electrogenic: creates an electrical potential (vs electoneutral) (vs. electoneutral) Postulated mechanism of Na+K+ ATPase Cardiac glycosidies (or cardiotonic steroids) inhibits Na+K+ ATPase (Treatment of congestive heart failure) Ca2+ ATPase [Ca2+]in ~ 0.1 μM [Ca2+]out ~ 1500 μM H+ pump of the mammalian stomach • Parietal cells of the mammalian gastric mucosa secrete HCl (0 secrete HCl (0.15M, pH 0.8) pH • H+ is derived from the carbonic anhydrase reaction reaction CO2 + H2O ↔ HCO3- + H+ • H+/K+ ATPase secrets H+ by an electroneutral secrets an electroneutral antiport of K+ HCl secretion by parietal cells Regulation of gastric acid secretion Treatment of acid reflux or heartburn Histamine antagonists Cimetidine (Tagamet) Ranitidine (Zantag) Famotidine (Pepcid) Proton pump inhibitors Omeprazole (Prilosec) Esomeprazole (Nexium) Group translocation • Simultaneous chemical modification of transporting molecules transporting molecules • Phosphoenolpyruvate-dependent phosphotransferase system (PTS) phosphotransferase system (PTS) simultaneously transports and phosphorylates sugars including glucose, fructose, mannose, Nacetylglucosamine etc. in bacteria Transport of glucose by the PEP-dependent phosphotransferase system (PTS) in bacteria syste bacte Ion gradient Ion gradient-driven active transport active transport Lactose permease of E. coli Glu Arg Glucose transport in intestinal epithelial cells ATP-ADP translocator Electrogenic ATP-ADP antiport process (ATP4- ↔ ADP3-) is driven by the membrane potential difference Structure of a neuronal cell Stimuli to open gated ion channels • Mechanosensitive channels – Local deformation of the bilayer deformation of the bilayer • Ligand-gated channels – Extracellular stimuli such as pH change and stimuli such as pH change and neurotransmitters • Signal-gated channels – Intracellular binding of a second messenger such as Ca2+ • Voltage-gated channels – Change in membrane potential Voltage-gated ion channels • Voltage-gated Na+ channels (Nav channels) • Voltage-gated K+ channels (Kv channels) (K • Voltage-dependent Ca2+ channels (Cav channels) Voltage-gated Na+ channels of neurons Voltage-gated K+ channels (Kv channels) The ball-and-chain model for inactivation Gating of Kv channel by the motion of voltage-sensor paddles “Inactivation ball” Action potential • Resting potential • Stimulation • Depolarization (“Rising phase”) phase • Peak • Repolarization (“Falling phase”) • Hyperpolarization (“Undershoot”) Generation of an action potential • A membrane depolarization is generated by a transient increase in the membrane’s permeability to Na+ (Nav channel) • Rapid repolarization past the resting potential to the K+ equilibrium potential (hyperpolarization) is caused by a transient increase in its increase in its permeability to K+ (Kv channel) Action potential propagation along an axon • • • • A local increase in the membrane potential induces the transient opening of the neighboring Na+ channels More and more Na+ ions diffuse into the nerve cell, causing a rapid increase in the membrane potential (membrane id depolarization) The K+ channels open while the Na+ channels close (Repolarization and hyperpolarization) (Repolarization and hyperpolarization) The K+ channels also close (Return to the resting potential) Nerve impulse velocity is increased by myelination Synapses • Electrical synapses – ~20 Å synaptic cleft – Direct electrical coupling – Rapid signal transduction transduction • Chemical synapses – ~200 Å synaptic cleft – Release of neurotransmitters from the presynaptic membrane – Receptors on the postsynaptic membrane Acetylcholine receptor is a ligand-gated cation channel cat • Ach binding allosterically induces the opening of channels to permit Na channels to permit Na+ and K+ ions to diffuse in to diffuse in and out, respectively • The resulting depolarization initiates a new resulting depolarization initiates new action potential • Acetylcholine is rapidly degraded by cety deg by acetylcholine esterase (AchE) Acetylcholine receptor ion channel Amino acids and their derivatives as neurotransmitters Patch-clamp techniques The patch-clamp technique Some diseases resulting from ion channel defects ...
View Full Document

This note was uploaded on 10/16/2010 for the course CHEM 60280 taught by Professor Ryu during the Spring '09 term at TCU.

Ask a homework question - tutors are online