Lecture 05 Ion Flux Through Membranes Flashcards
What is membrane transport
- membranes regulate flow of biomolecules into and out of cells
1. passive= energy INDEPENDENT, down concentration gradient (high to low)
2. active= energy DEPENDENT, against concentration gradient (low to high)
What are 2 types of passive transport?
- energy independent movement of molecules down concentration gradient (unaided or w/assistance of transmembrane proteins)
1. Simple diffusion
2. Facilitated diffusion
What molecules use simple diffusion?
-small, nonpolar, uncharged polar molecules diffuse freely across membrane
-steeper gradient the faster diffusion
Ex) O2, N2, ethanol, benzene, H2O, CO2, NH3, Urea
What molecules use facilitated diffusion?
-large and charged molecules unable to cross the membrane w/o facilitator protein to help movement
-proteins function as ion channels or transporters
-greatly increase rate of transport
Ex) polar=H20 use aquaporin uniporter
Ex) charged= Na+/K+/Cl- symporter, voltage gated Na+ channel (uniporter), Cl-/HCO3- antiporter
Ex) large= glucose transporter GLUT1 (uniporter)
Dont need energy just protein to help
What is a channel?
- contain core of polar residues that allow charged and polar molecules (ions/water) to move across membrane
- high throughput (millions per second)
What is a transporter?
- bind to a molecule on one side of the membrane, undergo conformation change to release molecule on other side of membrane
- induced either by binding of ligand or ATP
- less efficient than channels (transport few molecules b/c intermediate occluded state)
What are 2 things a defective amino acid transporter can lead to?
- Cystinuria= AR
2. Hartnup disease= AR
What is cystinuria?
- AR
- caused by defect in transport system responsible for uptake of dimeric a.a. Cystine and di basic a.a Arg, Lys, Ornithine
- results in formation of Cys crystals/stones in kidney
- positive nitroprusside test
- patients present with renal cholic (ab pain comes in waves like kidney stones)
What is hartnup disease?
- AR
- caused by defect in transporter for NON-polar or neutral a.a. (ex=Trp)
- found in kidneys and intestine
- manifest as failure to thrive, nystagmus (rapid eye movement), ataxia (lack of muscle coordination), tremor, photosensativity
What are ligand gated ion channels?
-responsive to the presence of ligands
-binding of ligand (NT/hormone) to ion channel causes conformation change in protein
-opening of channel, rapid transport of ions across membrane down concentration gradient and dissociate of ligand closes channel
Ex) glutamate R–> antagonist of R used to to alzheimers
What are voltage gated ion channels?
-open/close in response to membrane potential
-depolarization due to influx of + charged ions permitting specific ions to cross bilayer down concentration gradient
-found in neurons and excitable cells
Ex) Na+ channel
What do topical anesthetics like lidocaine do?
- inhibit Na+ channel
- blocks neurotransmission so don’t feel pain (ex dentist office)
- tetrodotoxin also inhibits Na+ channel
What is active transport?
- protein assisted, energy dependent movement of molecules AGAINST their concentration gradient
- primary and secondary
Primary active transport
-use energy from ATP hydrolysis to induce conformation change in transporter to allow molecule release
Ex) Na/K ATPase and Ca2+ ATPase
Secondary active transport
-use energy stored in a concentration gradient
-facilitated fission of diff. Molecule down its concentration gradient coupled to transport of a different molecule
1. Uniporter= transports molecules in 1 direction (downhill)
2. Cotransporter=
A. Symporter= same direction (Na/glucose)
B. Antiporter= opposite direction (Na+/Ca2+ exchanger NCX)
Na/glucose transporter 1 (SGLT1)
- in epithelial cells in renal tubules and SI
- unidirectional movement of Na+ and glucose across SI and renal tubules
- movement of Na+ down its concentration gradient provides energy to move glucose against its gradient
- Na+ gradient is reset by Na/K ATPase
How are new SGLT drugs using SGLT in renal tubules?
-blocking SGLT 1/2 might keep more glucose in intestines/kidneys to be urinated out, lowering blood sugar levels
Ex) INVOKANA
What is the Na/Ca exchanger (NCX)
- antiporter
- maintain low levels of intracellular calcium in cells
- import 3Na+ down concentration gradient and export 1Ca+ against its gradient
What is the transport mechanism in uptake of dietary monosaccharides?
- D glucose/galactose enter intesinal eptihalial cells along with Na+ by secondary active transport (SGLT1)
- Then transported across enterocyte into blood stream via facilitated diffusion using GLUT2
- Fructose transported only by facilitated diffusion down its concentration gradient using GLUT5 on apical and GLUT2 on basal side
- Na+ transported by SGLT1 delivered to blood using primary active transport Na/K ATPase on basolateral membrane
What do cardiotonic drugs do?
- ouabain/digoxin
- INHIBIT Na/K ATPase on cardiac myocytes
- leads to increase intracellular Na+ and secondary increase in Ca+ due to slowing of NCX
- increased Ca2+ results in stronger excitation contraction of heart muscle with each AP in CHF patients
How does defective chlorite transport lead to CF?
- CF caused by mutation in CF transmembrane conductance regulator (CFTR) gene–>defective protein
- CFTR=Cl- channel mediates active transport of Cl- from inside cells to outside in airways and sweat ducts using energy of ATP hydrolysis
- defective CFTR causes buildup of Cl- and SALT inside airway epithelial cells
- decreased water content of surface mucous layer surrounding airway epithelial cells leads to thicker mucus and bacterial infections
