Chapter 11 Reading Notes

Notes on Chapter 11

Use these notes as you read the text. These will not be collected, but as you write answers to these questions you will increase your comprehension, and you will be able to better articulate what you don't understand. Comments and suggestions are most welcome!

An introduction to membranes and their lipids.

Words that you should be able to define:

Micelle

Liposome

Bilayer

Important concepts:

Behavior of lipids in aqueous environments

What is the major driving force for the formation of micelles, liposomes and bilayers?

Transition temperature

Look at table 11-2, what generalizations can you make about fatty acid composition and the temperature that was used to culture E. coli?

Role of cholesterol in lipid fluidity

How does it increase fluidity?

How does it decrease fluidity?

Movement of lipids

What is the difference between lateral diffusion of a phospholipid and transbilayer diffusion? What is required for transbilayer diffusion?

Proteins in membranes and membrane fusion.

Words that you should be able to define:

Integral

Peripheral

Annexins

Hydropathy index

Fusion proteins

Integrins (CD18 is the beta subunit of an integrin, defects in this subunit cause leukocyte adhesion deficiency, page 386)

Type I, II, III, IV, V and VI integral proteins (Figure 11-14)

Important Concepts

What type of linkages/interactions hold proteins on membranes?

Secondary structure

What is the most common structural motif in membrane spanning proteins? What is the second most common? Can the hydropathy index be used to predict this second type of structure?

What is a lipid raft?

What is a caveolin?

Describe four examples of membrane fusion.

What are SNAREs and SNAPs?
How does the HA protein allow the flu virus DNA into a host cell?

Transport across membranes I: Passive Transport, no energy required

Words that you should be able to define:

simple diffusion

selectively permeable

facilitated diffusion

membrane potential (either chemical or electrical)
osmosis

transporters

permeases

aquaporins

Important concepts:

Why are the structures of many transporters not known?

What contributes to the thermodynamic barriers that impede membrane transport?

What driving forces allow passive diffusion to occur with transporters?

How are transporters analogous to enzymes?

How do tranporters differ from enzymes?

Give examples of locations of aquaporins.

How do aquaporins work? How is their proposed structure related to their function?

Where is the GluT1 glucose transporter found? How is the proposed structure of this transporter related to its function? How is it specific for glucose?

Michalis-Menton kinetics can be applied to transporters!

What is the value of Kt for D-glucose? For galactose? For L-glucose? What does Kt mean?

Comparison of Erythrocytes and Hepatocytes

The liver has GluT2 transporters and they have a Kt value of 66 mM. If blood glucose levels were 5 mM, which tissue would take up glucose? Make a graph of velocity of glucose uptake vs glucose concentration. Aren't you impatient to learn about the glucose transporters in muscle and adipocytes?? See box 11-2!

One last type of energy free (passive) transporters: Cotransport systems.

Look at figure 11-33 to see how the chloride-bicarbonate exchanger works to shuttle CO2 out of the tissues, into the blood as bicarbonate and then out of the lungs.

Active transport (Energy is required)

Be able to describe and give examples of 1° and 2° active transport.

We will discuss the free energy equations that are used for the transport of uncharged species.

Why is delta G°' equal to zero for membrane transport?
We will also do some practice calculations for various ratios of stuff inside to stuff outside. The book uses C2 to indicate the side that stuff is going "to" (analogous to P for products), and C1 for the side that stuff came from (analogous to S for substrates).
What will the delta Gt be for transporting stuff into a cell that has more of the stuff inside than out?

Another addition to the equation is required for the transport of charged species.

delta psi = membrane potential
Delta psi= (from - to)
What is the Delta Gt for moving choride ions into a cell, if the concentration of chloride is the same outside and inside the cell?

If a reaction or process is spontaneous, what is the sign of the value for Delta G? What is the sign of Delta G for a non spontaneous process/reaction?

There are four types of ATP dependent transporters. Be familiar with these. Where are they found (cell type and membrane type), what inhibits them? What do they transport? Be sure to read about the multidrug transporter. Note: the Fo subunit of the F-type ATP coupled transporter is not F(zero) it is F(letter o). The "o" stands for oligomycin. Oligomycin inhibits this type of transporter by blocking the ion's access to the membrane channel. We'll learn more about these F-type transporters that both make and break ATP later this semester.

Box 11-3 describes the transporter that is defective in the genetic disease, cystic fibrosis. We'll discuss this briefly in class.

We will discuss how the Na+/K+ ATP pump works. About 25% of your resting energy consumption is due to this pump! We will practice some manipulations of the Delta Gt for maintaining the Na+ and K+ gradients.

Another important example of 1° active transport is the Ca+2 pump.

Why is Ca+2 pumped out of the cytosol?
Where is it pumped in myocytes?

What drives 2° active transport. Why is it "secondary"?

The Na+/glucose symporter allows intestinal cells to accumulate glucose at very high concentrations. How does this work? The book uses Delta E in place of delta psi, I think this is a mistake. Be able to calculate the excess glucose concentration on the inside for a given set of Na+ concentrations inside and outside and a given membrane potential. Note: The book states that this transporter works in conjunction with GluT2 in the intestinal epithelial cells. The GluT2 transporter is in the liver. The GluT5 glucose transporter is on the blood vessel side of intestinal epithelial cells.

A few words about the calculations in the book on page 406. The book states that the flow of sodium ions has a difference in free energy of -25kJ. I played with the numbers and to get close to that value, the membrane potential must be -70 mV. Calculate the free energy for one mole of Na+ ions, then multiply that number by 2 moles of Na+ ions.

deltaG = 8.314J/moleK*310K ln (145/12) + (1 *96480J/volt*mole*-50x10-3volts) = -13.2 kJ/mole

2 moles Na+ *-13.2kJ/mole = -26.4 kJ (the book has -25kJ)

To calculate the amount of glucose that can be accumulated, change the sign on the Delta G for the transport of Na+ and solve for the ratio of C2/C1.

-26.4kJ = 8.314J/moleK*310K ln (C2/C1)
-26.4/(8.314*310) = 10.22
10.22 = ln (C2/C1)
e10.22 = C2/C1
27,597 = C2/C1
If C1 = 1 then C2 = 27, 597 which is roughly 30,000 times more glucose on the inside than on the outside.

This type of calculation is required for problem #8. For #10 use the above calculations to explain your answer.

What is an ionophore? See figure 11-45.

Be able to describe ion selective channels.

What are the three major differences between ion selective channels and ion transporters? Where are these channels often found?

Be able to describe the K+ channel.

Why is it selective for K+ ?
Why is work on this channel a landmark in biochemical research?

How does the nicotinic acetylcholine receptor work?

Why is it named nicotinic?
What is a muscarinic acetylcholine receptor?
How is it gated?

The neuronal Na+ channel is the basis for neuronal signalling.

How does this work?
Describe the "ball and chain" model.
How fast does this gate function?
What type of gate is it?

How do the toxins, tetrodotoxin, saxitoxin, dendrotoxin, bugarotoxin, tubocurarine, cobrotoxin exert their effects?

What is a porin?

Table 11-7 summarizes all of the types of transporters. Table 11-8 gives examples of diseases due to defective channels.

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