Hip
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If my naive understanding is right, within a cell an ATP molecule releases one of its 3 phosphate groups, when energy demands require it, a phosphate group being the energy form that cells can immediately utilise.
It is not the phosphate group itself that contains energy; the energy is actually contained in the chemical bond that attaches the phosphate group to the adenosine group.
You can think of a chemical bond as a compressed metal spring that joins and locks the phosphate and adenosine groups together. Because the spring is compressed, the spring contains energy, and when you break the chemical bond by removing a phosphate group, that energy in the compressed spring is released, and can do useful work.
Think of it like the compressed spring you have inside a cocked air rifle: because the air rifle spring is compressed, there is energy contained and stored in the rifle, which will be released when you later pull the trigger.
Conversely, when you re-attach a phosphate back onto the adenosine, it needs a supply of energy to do that, because you have to first compress the spring in order to attach the phosphate.
This re-attaching of a phosphate is like using the strength of your arms to cock the air rifle, where you are compressing the air rifle's spring.
And this is what happens in the mitochondria: when an ADP molecule returns to the mitochondria for recycling, the energy that the mitochondria generate is used to compress the spring in the bond which re-attaches a phosphate group to ADP to produce ATP. In that way, you store the energy in the ATP molecule's bonds, which like the cocked spring in an air rifle, is ready to be released whenever needed.
I am just wondering if this is more like a flywheel energy storage mechanism, which some green vehicles utilise. The flywheel stores a lot of kinetic energy, and so holds energy that is (almost) instantly available when needed. The flywheel slows as the vehicle absorbs useful energy from it, and then the fuel source is used to top up the flywheel's kinetic energy store.
Energy is found in one of two forms: kinetic energy (the energy of motion) and potential energy (a static situation where the energy is stored and ready to be liberated).
The energy in a flywheel is kinetic energy, because the flywheel is in motion.
The energy stored in a compressed spring (and a chemical bond) is potential energy, so in this aspect, the flywheel recycling analogy is not so appropriate for describing ATP/ADP; although the flywheel analogy does of course capture the idea of energy storage and recycling.
The potential energy stored in ATP is better thought of as a compressed, cocked spring, ready to release its energy.
So the ATP molecule, with once of its phosphate groups removed for useful work, has now become an ADP molecule, which by itself is cannot make available its phosphate groups as useful "energy packets" for the cell's consumption.
The ADP molecule (with 2 phosphate groups) can release one of its phosphate groups to provide further energy if there is a high energy demand. When this occurs, the ADP then becomes AMP (with 1 phosphate group).
To break down ADP into AMP in order to liberate energy, cells use the adenylate kinase reaction, in which two molecules of ADP combine to make one of ATP (which is then used for energy) and one of AMP.
However, unless there is an energy shortage emergency, my understanding is that the body does not normally further break down ADP to AMP in this way, because it is hard for the body to later recycle AMP back to ADP, and then ultimately back to ATP.
Because it is hard to recycle the AMP molecule back to ADP, the AMP just tends to get thrown away, which not only wasteful, but can also lead to a bit of a disaster, because then you are left with an acute shortage of these ADP molecules. It is this acute shortage of ATP/ADP molecules that leads to PEM, in the theory proposed by Myhill, Booth and McLaren-Howard.
By contrast, it is easy for cells to recycle to ADP back to ATP (provided the mitochondria are working properly). So under normal circumstances, I believe the body sticks with this, and does not break down ADP any further to extract more energy.
The reason it is proposed that ME/CFS patients do sometimes break down ADP further into AMP is because ME/CFS patients do not have enough energy supplied by their mitochondria (and/or because there is an impediment in the ADP to ATP recycling machinery), due to mitochondrial dysfunction, and so ME/CFS patients can very quickly enter into an energy shortage emergency, when they start to do any physical exercise which puts high demand on the energy supplies.
So during this energy shortage emergency that occurs in exercise, that's when the cells in the body start to break down ADP into AMP, just to extract every last ounce of energy, as energy is in such short supply (because the mitochondria are not able to supply enough energy to meet the high energy demands that physical exercise places on the body).
As mentioned, to break down ADP into AMP in order to liberate energy, cells use the adenylate kinase reaction, in which two molecules of ADP combine to make one ATP and one AMP.
This converting of 2 molecules of ADP into ATP plus AMP provides more energy, and gets you through the energy shortage emergency occurring during exercise; but then a short time later there is a major price to pay: because you have thrown away a lot of your ADP molecules by converting them to AMP, so now you have another problem — the problem of having not enough ADP and ATP molecules to transport the energy generated in the mitochondria into the cell.
So that then sends you into second energy metabolism emergency, this time not caused by a shortage of mitochondrial energy production, but by a shortage of the ATP/ADP molecules that are necessary to transport the energy generated in the mitochondria into the cell. It is this second energy emergency situation that creates the state of PEM, according to the theory and hypothesis proposed by Myhill, Booth and McLaren-Howard.
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