More notes on Membrane transport

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 G_t  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.

•  = membrane potential
• = from - to
• What is the  Delta G_t 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 DG?  What is the sign of DG 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 G_t 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  , 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.

DG = 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 DG 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)
• e^10.22 = 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 anwer.

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.