Week 5 - Transport Across Membranes Flashcards
Membranes
All organs with in the cell are surrounded by membranes, not jsut the plasma membrane
Fluid Mosaic Model of Membranes
Glycoproteins
Proteins that on the EXTRACELLURLAR surface of cell have carbohydrates attached to them
Transmembrane Proteins
What is the main structure?
What are the main amino acids?
Most of them are used in transporters and have alpha helical structures.
The alpha helix is very lipophilic (leu ioleu val, amino acids that have hydrophobic sidechains) it is very structureally and energetically stable in the membrane
**Transmembrane protien alpha helix strucutre are 19 to 21 amino acids long
Different types of membrane proteins..
What are the types of membrane transport?
Simple Diffusion
Facilitated Diffusion
Active Transport
Endocytosis
Simple Diffusion
Diffusion across a membrane.
No energy required, no particular direction. The amount diffused depends directly on the concentration of the substance
Facilitated Diffusion
Pore
Gated Channel
Carrier Protein
Diffusion of a molecule down its concentration gradient
Active Transport
Uses ATP to transport a substance against its concentration gradient
Kinetics of simpe (passive) diffusion vs carrier-mediated (facilitated) diffusion
Simple diffusion - linear relationship between rate of transport and concentration of transported molecule
Facilitated diffusion - Faster than simple at first but then when all of the tranporters are saturated it hits a max velocity..
Facilitated diffusion have a Km value (concentration of transpoftedm moledule at half Vmax). Higher Km is slower diffusion
Facilitated Diffusion
Carrier proteins/ transporters / permeases (several hundred of these types - Major Facilitator Superfamily, MFS)
Channels (regulated by three things - membrane potential the charge across membrane, ligand binding can open them, or by phosphorylation. *Concentration graadient will not affect this directly, the channels dont care what the concentration gradient is.
Pores
Aquaporins
Channels for cells to take in water
Kidney
Brain
Intestines
Basically any organ that uses a lot of fluid..
Dr. Agre classic experiment
Frog eggs, one is injected with RNA to express aquaporins, eggs with and without this RNA are put in a hypotonic solution.
The one with the RNA that expressed the aquaporins swelled while the unmodified eggs did not.
Aquaglycerolporins
Fat cells have them to carry triglycerides along with water accross the membrane
Facilitated Diffusion
BInding site
Ligand Binds
Conformational change in tranporter
This allows the ligand to be released on other side of membrane
High to Low concentration, down its conc gradient*
Human GLUTs
Usually 12 transmembrane subunits (alpha helixes)
THis is GLUT 1
GLUT transporter family
The different classes are structurally different, the ones in the same class are similar in structure.
GLUTS 1 - 5
Know 1 - 5…
GLUT 1,3 are ubiquitus
GLUT 4 regulated by insulin**
GLUT 4
Vesicles fuse with membrane to recrutit more GLUT 4 transporters when insulin binds to the receptor.. after insulin leaves the vesicles reform and the GLUT transporters are less..
Active Transport Energetics
Driven by ATP*
C1 is concentration from where the molecules is going to be transported
C2 is where its trasported to
Z is charge on ion (1 for Na, 2 for Ca) if the molecules are charged..
If delta G is pos it required energy
If delta G is neg it is spontanious..
Ion distribution across membrane.
Note which ones require energy to be transported. Use equation..
delta G = 2.303 RN Log (C2/C1) +( Z F delta V)
Secondary Active Transport
Driven by ion gradients - Na / K ATPase pump
3 sodiums , then it is phosphorylated releasing the sodium and taking in 2 potasiums to go back to other side where it is dephosphorylated
Digitalis Pupurea
Digoxin - used to increase HR and strenth of contractions
This molecule increases activity of Na / K ATPase so it increases the gradient across membrane in heart
Na / glucose symporter in intestine
No ATP involved directly (but it requires the ion gradient) so this is secondary active transort - glucose is transported againste its concentration gradient.. then glucose can be transported down its conc. grad into the blood stream.
Primary active transport uses ATP directly…
Summary Table of trasporters..
Know glucose, O2 and the ions
Saturation kinetics (Vmax)
ABC transporters
ATPase Cassette Transporters
ABC transporters - have a structure that specifically binds ATP.. 49 in the human genome
Drug Resistance Genes - Cancer
Cancer cells. Why does a chemical work at first to kill the cells and rid cancer but then cancer comes back and is resistant to the drug..
This is caused by increases efflux of the chemical***
P glyco protein is one of these transporters PG-P
Tangier Disease (TG)
Mutation in the ABCA1 gene
Causes SCA in ppl in there 20’s..
PGY1 gene mutation transporter protein.. .
Cystic Fibrosis
Disease associated with CFTR ABC gene..
Causes pulmonary issues..
Bronchiectasis, pneumothorax,
also skin - very high salt content..
Cane make males infertile
Deletion mutation of phenylalanine at position 508 this is most common mutation casuing disease..
Serine groups phosphorylated by PKA, this activates the regulatory domaine. PP2A dephosphorylates it.
It is an efflux transporter for Cl.
CFTR gene mutation
CFTR Protein function
Normal function of CFTR is to allow Cl- transport across cell membranes and to regulate transport of other ions via interactions with their transport proteins
Sweat Chloride Test
Salt detector can be put on skin to detect incrases salt..
A child that tastes salty when kissed will soon die.”
-European Folklore, Spain,1606
Sweat Gland
Key - when Na and Cl are pumped into the duct, it becomes hyperosmolar and water diffuses in and up the duct..
normally there is NaCl reabsorption as it is flowing out of body.. but in ppl who have a defect in the efflux transporter dont have this and they lose their salts (cystic fibrosis)
CFTR Sweat Gland
Outlined transporters are defective in cyctic fibrosis.. On bottom there are two cells that can transport Cl into gland, one still works.
Similar issues in lungs except not salt.. the flud the lungs secrete is not fluid to flush it out.. it is very mucousy and the lungs accumulate bacteria and dust etc that causes infection.
Bacterial infections are biggest problem for ppl with cystic fibrosis.. Usually the cause of death (anearobic like pseudomonas, clostridium)
Tetrodotoxin
Saxitoxin
A toxin that blocks sodium channels - produced by buffer fish
Saxitoxin from plankton - red tide
These are inhibitors that tightly bind to the sodium binding sites
Na Channel
3D structure of Na channels - doughnut
24 transmemrane proteins.. 4 groups of 6 to make doughtnut
Na channels are opened by action potentials that change the polarization of the membrane..
Neg charge on inside hold the pos lycin groups down and closes channel.. then action potential hits , reverses polarity and the channel opens
Nerve cells
Ca channel very similar
24 transmembrane proteins
1 - 4 domain
Very similar to Na channel.
Tetra-ethylammonium ion
How are channels selective on which ions they bind?
amino acid sequence that form the pore of the channel select which ion it transports***
Long QT syndrome
Causes torsades de pointes..
Syncope
Seizures
Sudden Death
The mutations in the channels that cause this are called channel mypoathys..
Epilepsy
Caused by mutations in genes that transport sodium channels..
Ionophores
Gramicidin
antibacterials, antivirals
Can move ions across membranses to dissipate the ion gradients.
Gramicicin actually forms a dimer that creates a pore in the membrane..
