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Biological Membranes and Transport
Simple diffusion
Simple diffusion - No transporter protein needed, no energy
expended
Simple diffusion of gases (O2, N2, CH4), slow diffusion of water
(high concentration)
Biological Membranes and Transport
Simple & Facilitated diffusion
Simple diffusion in living organisms
Impeded by selectively permeable membranes (high G‡)
Facilitated diffusion
Passive transport
permease
Bind substrate with stereochemical specificity, lots weak interactions
Span bilayer, channel lined with hydrophilic amino acids
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
Kt = constant similar to Km, combination of rate constants characteristic
of each transport system (measure of affinity of transporter for glucose)
Lower Kt, higher affinity
Biological Membranes and Transport
Glucose transporter of erythrocytes
GluT1 specific for D-glucose, Kt = 1.5 mM
D-mannose (Kt = 20 mM), D-galactose (Kt = 30 mM),
L-glucose (Kt > 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 Vmax )
(3) specificity
Lower
[glucose]
High [glucose]
~5 mM, 3x Kt
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 (Kt = 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
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 HCO3- by 106
Two anions move at once (HCO3- and Cl- in opposite directions)
Cotransport
Biological Membranes and Transport
Glucose transporter
Chloride/Bicarbonate
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)
Biological Membranes and Transport
Primary active transport: ATP-dependent active transporters
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)
Digitalis treat congestive heart failure
inhibits Na+ out, so more Na+ in cell
more Na+ activates Na+-Ca2+ antiporter in cardiac muscle
more Ca2+ 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 Claccompanied 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