by Loren A. Bertocci, Ph.D

In my last three articles (Part 1, Part 2, Part 3) , I wrote about the adaptations that occur, as a result of training, within the myocardium and outwards towards the spaces outside of skeletal muscle, and how fuel is handled within muscle cells.  But I am not done yet, because there are a lot more adaptations that occur, as a result of endurance type training, within muscle cells. For this article, I am going to limit the topic to some of the important things that involve oxygen.

It is likely that everyone reading this article knows that oxygen (the molecule O2) is one of the molecules in the atmosphere that we all need to breath. In past articles, particularly the ones addressing the central (myocardial) adaptation and the peripheral adaptation that triggers the growth of new capillaries, O2 played an important role. Based solely on those two articles and what is commonly seen in the lay press, it is natural to treat O2 as both indispensable and harmless. Aside from the absolute requirement for it to be present at the site where ATP is synthesized, it is not that simple. To help understand some of what O2 actually does, I will first track an O2 molecule as it moves off of an oxygenated red blood cell and ends up participating in ATP synthesis.

The O2 molecule that is unloaded off the hemoglobin of an oxygenated red blood cell must cross two barriers: the wall of the capillary and the outer membrane of the muscle cell. After it crosses these two barriers, it binds to myoglobin. It moves in this direction very easily because the concentration of O2 in the arterial end of a capillary bed is roughly 100x greater than the concentration of O2 bound to myoglobin. From there, the O2 moves away from myoglobin to where it binds to the outside, and then diffuses to the inside, of a mitochondrion. It moves in this direction very easily because the concentration of O2 bound to myoglobin is roughly 10x greater than the binding constant of O2 to a mitochondrion. All together, O2 moves from the blood to the mitochondria down a roughly 1000-fold concentration gradient. The meaning of this is that there is virtually no O2 inside a muscle cell that is not either bound to myoglobin or found inside of mitochondria. Some of this information was found in the article I published in early March 2017. For most people, who imagine that we need an abundant amount of O2 floating around in order to perform intense exercise, this probably seems counter-intuitive.

So, as a molecule of O2 moves though the mitochondria, and eventually to participate in the process of allowing the ATP synthase to actually make ATP, it has to pass through a series of steps called the electron transport chain. During two of these steps, in an interesting evolutionary adaptation, a small number of these O2 molecules combines with one of these electrons (remember the electron transport chain?) to make something called a superoxide ion (chemical symbol O2). This is an extremely toxic product and, among other things, can digest both proteins and cell membranes. What matters in this setting is that the more intense the exercise activity, the faster the flux down the electron transport chain, and the more O2 is made. So, it is the actual intensity of the exercise itself that increases the rate of O2 produced. Much of the cellular damage that occurs during heavy exercise is due to such a chemical attack.

It now gets a bit more interesting. Mitochondria already make an enzyme, superoxide dismutase, that removes this extra electron from O2. And your cells have another enzyme, catalase, which removes the resultant molecule of dissolved O2 from the cell. So, at its simplest level, after a mitochondrion makes one of these toxic O2 molecules, it then makes the enzymes necessary to remove it. Seems wasteful, right? Well, not so fast. It seems that mitochondria can sense the presence of O2 to trigger the stimulation of the growth of new mitochondrial protein. In a setting of increased mitochondrial protein, because there is such an increase in the enzymes of the electron transport chain, the actual rate of flux down any ONE such chain actually decreases. As an analogy, imagine that you need to pump 100 liters of water per minute. If you have only one garden hose, the water velocity is very high and some drops of water might leak out of the spigot or sprayer. On the other hand, if you have ten garden hoses, the average velocity of water flow down any one hose is one tenth what it was with only one hose, so there is much less water pressure and much less of a chance of water leakage. It works the same way with the electron transport chain. After making new mitochondrial protein, there is a reduction in the rate of O2 production from any one individual mitochondrion and, therefore, an attenuation of O2-mediated muscle cell damage. Again, as I wrote above, this is an elegant evolutionary adaptation.

So, from a practical perspective, what does this all mean to the athlete or coach? Anything the athlete does to increase the content of mitochondrial protein will lessen the net production of O2 mediated muscle cell damage. It also means that dietary supplements known to contain molecules that stimulate an increase of mitochondrial content will augment any endurance-training program. It is for this reason that several of the molecules found in Origins by Pangea were included in the mixture.

If any of you have any specific questions, including any greater details about any of this, please do not hesitate to ask me directly.

Pangea Origins is supported by real science and was formulated after 20 years of research into the science of endurance athletes.