Week 5 - Transport Across Membranes

Question 1

Membranes

Answer 1

All organs with in the cell are surrounded by membranes, not jsut the plasma membrane

Question 2

Fluid Mosaic Model of Membranes

Answer 2

Question 3

Glycoproteins

Answer 3

Proteins that on the EXTRACELLURLAR surface of cell have carbohydrates attached to them

Question 4

Transmembrane Proteins

What is the main structure?

What are the main amino acids?

Answer 4

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

Question 5

Different types of membrane proteins..

Answer 5

Question 6

What are the types of membrane transport?

Answer 6

Simple Diffusion

Facilitated Diffusion

Active Transport

Endocytosis

Question 7

Simple Diffusion

Answer 7

Diffusion across a membrane.

No energy required, no particular direction. The amount diffused depends directly on the concentration of the substance

Question 8

Facilitated Diffusion

Answer 8

Pore

Gated Channel

Carrier Protein

Diffusion of a molecule down its concentration gradient

Question 9

Active Transport

Answer 9

Uses ATP to transport a substance against its concentration gradient

Question 10

Kinetics of simpe (passive) diffusion vs carrier-mediated (facilitated) diffusion

Answer 10

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

Question 11

Facilitated Diffusion

Answer 11

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

Question 12

Aquaporins

Answer 12

Channels for cells to take in water

Kidney

Brain

Intestines

Basically any organ that uses a lot of fluid..

Question 13

Dr. Agre classic experiment

Answer 13

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.

Question 14

Aquaglycerolporins

Answer 14

Fat cells have them to carry triglycerides along with water accross the membrane

Question 15

Facilitated Diffusion

Answer 15

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*

Question 16

Human GLUTs

Answer 16

Usually 12 transmembrane subunits (alpha helixes)

THis is GLUT 1

Question 17

GLUT transporter family

Answer 17

The different classes are structurally different, the ones in the same class are similar in structure.

Question 18

GLUTS 1 - 5

Answer 18

Know 1 - 5…

GLUT 1,3 are ubiquitus

GLUT 4 regulated by insulin**

Question 19

GLUT 4

Answer 19

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..

Question 20

Active Transport Energetics

Answer 20

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..

Question 21

Ion distribution across membrane.

Note which ones require energy to be transported. Use equation..

Answer 21

delta G = 2.303 RN Log (C2/C1) +( Z F delta V)

Question 22

Secondary Active Transport

Answer 22

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

Question 23

Digitalis Pupurea

Answer 23

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

Question 24

Na / glucose symporter in intestine

Answer 24

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…

Question 25

Summary Table of trasporters..

Answer 25

Know glucose, O2 and the ions Saturation kinetics (Vmax)

Question 26

ABC transporters ATPase Cassette Transporters

Answer 26

ABC transporters - have a structure that specifically binds ATP.. 49 in the human genome

Question 27

Drug Resistance Genes - Cancer

Answer 27

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

Question 28

Tangier Disease (TG)

Answer 28

Mutation in the ABCA1 gene Causes SCA in ppl in there 20's..

Question 29

PGY1 gene mutation transporter protein.. .

Question 30

Cystic Fibrosis

Answer 30

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.

Question 31

CFTR gene mutation

Answer 31

Question 32

CFTR Protein function

Answer 32

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

Question 33

Sweat Chloride Test

Answer 33

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

Question 34

Sweat Gland

Answer 34

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)

Question 35

CFTR Sweat Gland

Answer 35

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)

Question 36

Tetrodotoxin Saxitoxin

Answer 36

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

Question 37

Na Channel

Answer 37

Question 38

3D structure of Na channels - doughnut

Answer 38

24 transmemrane proteins.. 4 groups of 6 to make doughtnut

Question 39

Na channels are opened by action potentials that change the polarization of the membrane..

Answer 39

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

Question 40

Ca channel very similar

Answer 40

24 transmembrane proteins 1 - 4 domain Very similar to Na channel.

Question 41

Tetra-ethylammonium ion

Question 42

How are channels selective on which ions they bind?

Answer 42

amino acid sequence that form the pore of the channel select which ion it transports\*\*\*

Question 43

Long QT syndrome

Answer 43

Causes torsades de pointes.. Syncope Seizures Sudden Death The mutations in the channels that cause this are called channel mypoathys..

Question 44

Epilepsy

Answer 44

Caused by mutations in genes that transport sodium channels..

Question 45

Ionophores Gramicidin

Answer 45

antibacterials, antivirals Can move ions across membranses to dissipate the ion gradients. Gramicicin actually forms a dimer that creates a pore in the membrane..