Biological Membranes and Transport Simple diffusion Simple diffusion - No transporter protein needed, no energy expended Simple diffusion of gases (O 2, N 2, CH 4 ), slow diffusion of water (high concentration)

Simple diffusion in living organisms Impeded by selectively permeable membranes (high  G ‡ ) permease Facilitated diffusion Passive transport Bind substrate with stereochemical specificity, lots weak interactions Span bilayer, channel lined with hydrophilic amino acids Biological Membranes and Transport Simple & Facilitated diffusion

Biological Membranes and Transport Facilitated diffusion (Passive transport) Aquaporins (AQPs) Create hydrophilic transmembrane channel for passage of water (no ions) Erythrocytes (red blood cells), proximal renal tubule cells, vacuole

Biological Membranes and Transport Facilitated diffusion (Passive transport) Glucose transporter of erythrocytes With glucose transporter glucose enters erythrocyte at rate ~50,000 higher than without the transporter

Biological Membranes and Transport Glucose transporter of erythrocytes Think back to enzyme/substrate kinetics Glucose outside cell = substrate Glucose inside cell = product Glucose transporter = enzyme K t = constant similar to K m, combination of rate constants characteristic of each transport system (measure of affinity of transporter for glucose) Lower K t, higher affinity

Biological Membranes and Transport Glucose transporter of erythrocytes GluT1 specific for D-glucose, K t = 1.5 mM D-mannose (K t = 20 mM), D-galactose (K t = 30 mM), L-glucose (K t > 3000 mM) Hallmarks of passive transporter: (1) high rate of diffusion down concentration gradient (2) saturability (GluT1 is nearly sat’d with substrate and operates near V max ) (3) specificity High [glucose] ~5 mM, 3x K t Lower [glucose]

Biological Membranes and Transport Glucose transporter of liver GluT2 transports glc out of hepatocytes when liver glycogen (stored sugar) is broken down to replenish blood glc GluT2 (K t = 66 mM) can respond to increased levels of intracellular glc by  n  outward transport Glucose transporter of muscle/adipose GluT4 transporter Muscle(glycogen)/adipose(triacylglycerols) take up excess glc (> 5mM)

Biological Membranes and Transport

Glucose transporter Type I diabetes mellitus, juvenile onset, insulin-dependent diabetes Insulin-producing cells have been destroyed Inability to release insulin (mobilize glc transporters) results in low rate of glc uptake High blood glucose Type II diabetes mellitus, adult onset, noninsulin-dependent diabetes Do make and release insulin Resistance to action of insulin Number and affinity of insulin receptors may be reduced Abnormal activation of glc transporters Obesity Medium/High blood glucose Diabetes insipidus genetic defect in aquaporin 2 leading to impaired water absorption by kidney

Biological Membranes and Transport Transport of Chloride/Bicarbonate across Erythrocyte Membrane Chloride-bicarbonate exchanger  permeability of erythrocyte membrane to HCO 3 - by 10 6 Two anions move at once (HCO 3 - and Cl - in opposite directions) Cotransport

Biological Membranes and Transport Chloride/Bicarbonate Glucose transporter

Biological Membranes and Transport Active transport Movement against a concentration gradient Accumulate solute above equilibrium point Thermodynamically unfavorable, coupled to exergonic process Primary active transport - directly coupled to ATP cleavage Secondary active transport - endergonic transport coupled to exergonic transport (went through primary first)

P-type Active cotransport of Na + and K + Reversibly phosphorylated by ATP Biological Membranes and Transport Primary active transport: ATP-dependent active transporters

P-type - mechanism Active cotransport of Na + and K + Biological Membranes and Transport Primary active transport: ATP-dependent active transporters

P-type Active cotransport of Na + and K + 25% of total energy consumption of a human at rest Inhibitors - ouabain and digitoxigenin (O+D = digitalis) Digitalistreat congestive heart failure inhibits Na + out, so more Na + in cell more Na + activates Na + -Ca 2+ antiporter in cardiac muscle more Ca 2+ in cell, strengthens heart muscle contractions Biological Membranes and Transport Primary active transport: ATP-dependent active transporters

F-type (bacteria, mitochondria, chloroplasts) & V-type (vacuole, lysosomes, endosomes, Golgi) Acidifies organelles & pumps protons Transmembrane pore for protons Biological Membranes and Transport Primary active transport: ATP-dependent active transporters

F-type Catalyze uphill movement of protons (ATP hydrolysis) AND downhill proton flow to drive ATP synthesis (ATP synthases) Biological Membranes and Transport Primary active transport: ATP-dependent active transporters

Defective Cl- ion channel in cystic fibrosis Symptoms: obstruct gastrointestinal and respiratory tracts, bacterial infections, death earlier in life due to respiratory insufficiency Defective gene for cystic fibrosis transmembrane conductance regulator (CFTR) - mutation involves deletion of Phe (improper folding) and reduced Cl- movement and improper phosphorylation In CF patients Cl - channel not working properly, less export of Cl- accompanied by diminished export of water leading to mucus on cell surface becoming dehydrated, thick, sticky (Staph & Pseudomonas bacteria grow here really well!) Normally thin layer of mucus in lungs Biological Membranes and Transport Primary active transport: ATP-dependent active transporters

Biological Membranes and Transport