1. Transport may involve ions, which are of central importance in the functioning of cells.

• Of particular imporance is the fact that concentrations of Na⁺ and Cl^- are high outside the cell (as they are in sea water!!!!) and concentrations of K⁺ and trapped organic anions are high within cells..

Component	Intracellular Concentration (mM)	Extracellular Concentration (mM)
Na+	5-15	145
K+	140	5-15
Cl-	5-15	110
Organic ions	high	0

2. Carrier proteins are important for transport of many types of substances across both external and internal cell membranes.

• Simple, "Fick's Law", diffusion, down a concentration gradient from high to low concentration, is only found for small hydrophobic molecules, such as steroid hormones, and gases. These substances move across membranes without the aid of a protein channel.
• Transport across membranes is mostly through protein channels. Diffusion shows net movement from high concentration to low concentration. Net movement up the concentration gradient, from low to high concentrations, must have energy supplied from somewhere. (fig. 11-3.1, Lodish) (fig. 11-3.2, Lodish) (fig. 11-3.3, Lodish)
• Glucose is moved into cells by facilitated diffusion through a uniport transporter protein that shows enzyme-like kinetics. There is a maximum rate of transport (flux), even if the concentration difference between the two sides of the membrane is very high. (fig. 11-4, Lodish)

• Most mammalian cells use the GLUT1 uniport transporter protein to moved glucose across cell membranes. All GLUT proteins likely have 12 alpha-helical, membrane-spanning, segments.
• In animal cells, such as those lining our intestine, glucose and other solutes may be moved into cells by symport cotransport with an ion, usually Na⁺. Here is a cartoon of the facilitated diffusion cotransport system. Glucose moves into the epithelial cells of the intestine against the concentration gradient for glucose. This seems to be against the laws of physics. But, the concentration for Na⁺ is in the correct direction. Since Na⁺ is at such high concentrations outside the cell, relative to those inside, it is the concentration gradient which drives the glucose into the cells.

An article about high fructose corn syrup, a common sweetener in foods, notes that while glucose is moved from the intestinal lumen into cells of the intestinal epithelium by a sodium dependent transporter, fructose is transported further down in the intestine by a non-sodium-dependent process. For a discussion of the controversy over the dangers of high fructose corn syrup, see an article in business section of the Sunday New York Times, July 2, 2006.

• The Na⁺/K⁺ pump removes Na⁺ from the cell by active transport keeping Na⁺ concentrations low. ATP provides the energy to move Na⁺ against its concentration gradient, from low to high concentration. Three Na⁺ are moved outwards and two K⁺ are moved inwards for each ATP hydrolyzed to ADP and phosphate. This is an example of a P-class pump. (fig. 11-9, Lodish)
• Osmotic balance is maintained in animal cells by the Na⁺/K⁺ pump. Most cell membranes are permeable to K⁺ and Cl^- so they diffuse where they need to and don't contribute to the osmotic pressure. And, the osmotic pressure created by the impermeable organic anions within cells is balanced by the "effective" impermeability of the cell membrane to Na⁺. If some Na⁺ gets into the cell by cotransport, then it is just going to be pumped right back out again. Now, imagine that the pump stops working. This will destroy the effective impermeability of the membrane to Na⁺ and the only impermeable ions left will be the organic anions inside the cell. Water will rush into the cell and the cell will burst.
• Other types of pumps include the V- and F-class proton pumps and the ABC superfamily of pumps. The section in Lodish about these pumps is required reading.

All text and images, not attributed to others, including course examinations and sample questions, are Copyright, 2009, Thomas J. Herbert and may not be used for any commercial purpose without the express written permission of Thomas J. Herbert.