Molecules Move

         Figure 1. A section of a schematic of insulin-induced translocation of glucose transporter 4. Insulin binding to its receptors initiates GLUT4-containing vesicles to fuse with the cell membrane. Modified from Wang et al. 2020.

Fish in freshwater consistently gain water from the environment. This is because water follows the rules of physics and follows a gradient from high water to low water. There is more water in the freshwater pond than in the fish’s cells since the cells contain concentrations of other stuff, salts, proteins, etc. One way to envision this is to put percentage values on the solution. A freshwater pond might have 99.8% water and 0.2 percent other stuff, while fish blood and cells are about 99.1% water and 0.9 percent dissolved stuff, mainly salt (0.8%). Water, following a concentration gradient, high to low, flows faster from 99.8% to 99.1%. I mention that it flows faster in one direction because water, if not prevented by some barrier, will move both ways, but more and faster into the fish.

The difference is not massive, and that’s good for the fish. The larger the concentration gradient, the faster the water will move. The fish also has ways to prevent water from flowing in. Thick scales, for example, prevent the water from moving into some areas of the body. However, the fish opens its mouth to eat, and water must also flow across the gills nearly constantly so the fish get oxygen. This is the main area where water takes the opportunity to flow into the fish’s cells/blood. The movement of oxygen into the gills (and blood vessels within) is also molecular movement down the concentration gradient. 

Fish living in freshwater get rid of excess water by peeing a lot. 

This movement of water across a cell membrane is called osmosis. It’s a biology 101 topic that hoards of students freak out about each year. The concept may be challenging when first encountered, but to me, it is fundamental: Things move from high to low. Figure out the concentration of what is moving and go downhill.

Fish in seawater, which is 96.5 percent water and 3.5 percent dissolved stuff, mainly salt, have the opposite problem of freshwater fish. These fish lose water to the ocean: fish blood has 99.1 % water, while seawater is 96.5 %, thus downhill movement 99.1 toward 96.5. These fish need to drink seawater to maintain water concentrations. But I hear you say that the water has a high salt concentration, which would exacerbate the problem. Our ocean fish has special cells in its gills that actively move chloride out, and sodium follows due to another rule of physics: opposites attract. Chloride is a negatively charged particle, while sodium is positively charged; thus, the opposites attract rule works. Our ocean-going fish also concentrate water exiting their body (pee) via the kidney to a great degree, ensuring not much water is lost that way.

Molecular movements are critically important in our bodies. Sodium and chloride are moved against their concentration gradients (using cell energy, more later) to set up the function of nerve cells; nerve firing is a change in the electric charges between the inside and outside of the cell. When the nerve gets a signal to fire, sodium channels open, and these positively charged particles move into the nerve cells. This change in electric charge is called a change in membrane potential, which causes more sodium channels to open, and a domino effect is born. Thus, a signal travels down the nerve cell, reaching, perhaps, the brain, which then responds (thinks) and sends a signal back or to other parts of the body as appropriate.

The movement of molecules is essential to keep cells and bodies alive. Much of the movement occurs passively, without the body using energy, and this always follows the rules of physics: down the gradient. However, the body needs to move molecules against the gradient, as above, to set up fast passive movement, or it wants to move hard-to-move molecules, for example, large molecules, where it wants them to go. Energy is required for this. Cell energy is ATP, which stands for Adenosine Triphosphate. ATP is created by using the potential energy from the food we eat. We can’t use, for example, the sugar in our food directly to do cellular work; we must convert it to ATP. Most of this occurs within the mitochondria that are within our cells. Glucose, blood sugar, is our most readily available food molecule. 

Thus, glucose is one of those molecules our body needs to move. We want glucose to be where we need it to be. Because of its importance and its connection with diabetes, the movement of glucose is a focus of study. The amount of detail about the movement of this molecule is staggering. I had no idea of the complexity.

First, glucose can move passively down its own concentration gradient, similar to osmosis above, but since it is not water, we term this diffusion. This works, for example, in our gut when food is digested into smaller and smaller particles, some of which end up as glucose. This can directly pass through the lining of our intestines into our cells lining the intestine, and then into our bloodstream. 

The movement of glucose into other body cells is more complex, and there is more complexity in movement in different areas of the body, for example, in muscle or fat tissue. Researchers have identified at least 10, and there may be many more, molecules that aid glucose transport, called glucose transporters; sometimes, they name things right. These are abbreviated GLUTs. As you might know, I’m not a fan of acronyms because they are overused. However, this is a pretty good one. Let me focus on just a few of the transporters.

GLUT1 and GLUT3 are protein channels in most body cells. They allow the facilitated diffusion of glucose. As blood glucose rises, glucose follows its concentration gradient, moving into the cells. As glucose is used in the cells to make cellular energy, ATP, the glucose level drops in the cell, and more glucose moves in.

GLUT4 is found in muscle, adipose cells, and probably other cells. This transporter is in the cell membranes and as vesicles inside the cells. It reacts to insulin. When insulin is present, more vesicles move to the surface of the cells, setting up more entry points for glucose to move into the cells.

This is just the tip of the molecular movement iceberg. Stay tuned; I’ll return to this topic, maybe with sharks and how their blood’s chemical makeup alters osmosis and physiology.

Sources and Further Readings:

Any biology textbook.

Moyle PB, and Cech JJ. 1988. Fishes: An introduction to ichthyology. Prentice Hall. Englewood Cliffs, NJ.

Wang T, Wang J, Hu X, Huang XJ, Chen GX. Current understanding of glucose transporter 4 expression and functional mechanisms. World J Biol Chem. 2020 Nov 27;11(3):76-98. doi: 10.4331/wjbc.v11.i3.76. PMID: 33274014; PMCID: PMC7672939.