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Transport Across a Cell Membrane
The cell membrane is one of the great multi-taskers of biology. It provides structure for the cell, protects cytosolic contents from the environment, and allows cells to act as specialized units. A membrane is the cell’s interface with the rest of the world - it’s gatekeeper, if you will. This phospholipid bilayer determines what molecules can move into or out of the cell, and so is in large part responsible for maintaining the delicate homeostasis of each cell.
Some cells function best at a pH of 5, while others are better at pH 7. The steroid hormone aldosterone is made in the adrenal gland, but affects mostly the kidney. Sodium is more than ten times more concentrated outside of cells rather than inside. If our cells couldn’t control what crossed their membranes, either no molecules would make it across, or they’d be traveling willy-nilly and the internal environment would always be in flux. It’d be like taking every item on a menu and blending it together before serving (not the tastiest idea).
So how do cells maintain different concentrations of proteins and molecules despite the pressures on them to be homogenous? Cell membranes are semipermeable, meaning they have control over what molecules can or cannot pass through. Some molecules can just drift in and out, others require special structures to get in and out of a cell, while some molecules even need an energy boost to get across a cell membrane. Each cell’s membrane contains the right mix of these structures to help that cell keep its internal environment just right.
Movement Across a Membrane and Energy
There are two major ways that molecules can be moved across a membrane, and the distinction has to do with whether or not cell energy is used. Passive mechanisms like diffusion use no energy, while active transport requires energy to get done.
Diffusion: the Simple and the Facilitated
Diffusion is the movement of particles down their gradient. A gradient is any imbalance in concentration, and moving down a gradient just means that the particle is trying to be evenly distributed everywhere, like dropping food coloring in water. This is what happened when we made our granola - a bunch of separate ingredients came together and spread out across the whole mixture. We call this evening-out moving “downhill”, and it doesn’t require energy. The molecule most likely to be involved in simple diffusion is water - it can easily pass through cell membranes. When water undergoes simple diffusion, it is known as osmosis.
Simple diffusion is pretty much exactly what it sounds like – molecules move down their gradients through the membrane. Molecules that practice simple diffusion must be small and nonpolar*, in order to pass through the membrane. Simple diffusion can be disrupted if the diffusion distance is increased. If the alveoli in our lungs fill with fluid (pulmonary edema), the distance the gases must travel increases, and their transport decreases. Facilitated diffusion is diffusion that is helped along (facilitated by) a membrane transport channel. These channels are glycoproteins (proteins with carbohydrates attached) that allow molecules to pass through the membrane. These channels are almost always specific for either a certain molecule or a certain type of molecule (i.e. an ion channel), and so they are tightly linked to certain physiologic functions. For example, one such transporter channel, GLUT4, is incredibly important in diabetes. GLUT4 is a glucose transporter found in fat and skeletal muscle. Insulin triggers GLUT4 to insert into the membranes of these cells so that glucose can be taken in from the blood. Since this is a passive mechanism, the amount of sugar entering our cells is proportional to how much sugar we consume, up to the point that all our channels are being used (saturation). In type II diabetes mellitus, cells do not respond as well to the presence of insulin, and so do not insert GLUT4 into their membranes. This can lead to soaring blood glucose levels which can cause heart disease, stroke, and kidney failure.
Sometimes the body needs to move molecules against their gradient. This is known as moving “uphill”, and requires energy from the cell - imagine how much easier it is to shake the trail mix together than it would be to then separate all the pieces again. This is most obvious in the sodium-potassium pump (Na+/K+ ATPase) that helps maintain resting potential in the cell. This protein uses the energy released from hydrolysis of ATP (adenosine triphosphate) to pump three sodium ions out of and two potassium ions into the cell. ATP is an energy molecule, and when hydrolysis happens, it gets broken down to release the energy that was stored in its chemical bonds. Transport that directly uses ATP for energy is considered primary active transport. In this case, that’s moving sodium from a concentration of 10mM to one of 145 mM. A similar gradient is being surpassed with potassium, whose intracellular and extracellular concentrations are 140mM and 5mM, respectively. Since these types of transporters are so costly in terms of energy, they are relatively rare. One other location for such an ATP pump is the proton/potassium exchanger (H+/K+ ATPase) found in the stomach. These proton pumps are responsible for creating the acidic environment of the stomach, and can cause acid reflux. Proton pump inhibitors like omeprazole are prescribed to patients with ulcers or acid reflux to help reduce the acidity of their gut.
Sodium potassium pump. As you can see, transmembrane channels on either side of the pump allow the ions to flow down their gradient.
Secondary active transport moves multiple molecules across the membrane, powering the uphill movement of one molecule(s) (A) with the downhill movement of the other(s) (B). For example, SGLT2 is a glucose transporter that allows glucose (Molecule A) into our cells (against its gradient) by bringing in a sodium molecule (Molecule B) as well. Remember, sodium wants to get inside the cell, and the energy released by it traveling down its gradient is enough to power glucose into the cell. Since both molecules moved in the same direction, this molecule is known as a symporter. Proteins that allow molecules to go in opposite directions are antiporters – one great example of this is the sodium/calcium exchanger used to restore cardiomyocyte (heart cell) calcium concentrations after an action potential. An influx of calcium causes the heart to contract, and the antiporter pushes calcium (Molecula A) out against its gradient, while bringing in a sodium ion (Molecule B) to let the heart relax.
You may notice that many of these secondary active transporters use sodium to propel other molecules against their gradients. This is one major explanation for why the sodium/potassium pump is so important – that one molecule helps set up the needed gradient to allow for the movement of many chemicals into and out of the cell. In fact, this relationship is taken advantage of in certain heart disease medications. Digoxin is given to patient with atrial fibrillation (abnormal, fast heart rate) and it inhibits the sodium/potassium pump. This leads to the accumulation of intracellular sodium, which actually causes the sodium/calcium pump to change directions! Now sodium is being pumped out and calcium being brought in – making heart contractions stronger.
Transport across a cell membrane is a tightly regulated process, because cell function is highly dependent on maintain strict concentrations of various molecules. When a molecule moves down its concentration gradient is it participating in passive transport; moving up the concentration gradient requires energy making it active transport.
|Polar molecules, larger ions
|GLUT4 / Diabetes Mellitus Type II
|Primary active transport
|Molecules moving against their gradient coupled to the hydrolysis of ATP
|Sodium-potassium pump, proton pump / atrial fibrillation, acid reflux
|Secondary active transport
|Molecule going with + molecule going against gradient
|Sodium-calcium exchanger, SGLT2