From Dr. Sarah Myhill’s wonderful website:

“The job of mitochondria is to supply energy in the form of ATP (adenosine triphosphate). This is the universal currency of energy. It can be used for all sorts of biochemical jobs from muscle contraction to hormone production. When mitochondria fail, this results in poor supply of ATP, so cells go slow because they do not have the energy supply to function at a normal speed. This means that all bodily functions go slow.

Every cell in the body can be affected

The following explains what happens inside each cell:

ATP (3 phosphates) is converted to ADP (2 phosphates) with the release of energy for work. ADP passes into the mitochondria where ATP is remade by oxidative phosphorylation (ie a phosphate group is stuck on). ATP recycles approximately every 10 seconds in a normal person – if this goes slow, then the cell goes slow and so the person goes slow and clinically has poor stamina ie CFS.

Problems arise when the system is stressed. If the CFS sufferer asks for energy faster than he can supply it, (and actually most CFS sufferers are doing this most of the time!) ATP is converted to ADP faster than it can be recycled. This means there is a build up of ADP. Some ADP is inevitably shunted into adenosine monophosphate (AMP -1 phosphate). But this creates a real problem, indeed a metabolic disaster, because AMP, largely speaking, cannot be recycled and is lost in urine.

Indeed this is the biological basis of poor stamina. One can only go at the rate at which mitochondria can produce ATP. If mitochondria go slow, stamina is poor.

If ATP levels drop as a result of leakage of AMP, the body then has to make brand new ATP. ATP can be made very quickly from a sugar D-ribose, but D-ribose is only slowly made from glucose (via the pentose phosphate shunt for those clever biochemists out there!). This takes anything from one to four days. So this is the biological basis for delayed fatigue.

However there is another problem. If the body is very short of ATP, it can make a very small amount of ATP directly from glucose by converting it into lactic acid. This is exactly what many CFS sufferers do and indeed we know that CFS sufferers readily switch into anaerobic metabolism. However this results in two serious problems – lactic acid quickly builds up especially in muscles to cause pain, heaviness, aching and soreness (“lactic acid burn”), secondly no glucose is available in order to make D-ribose! So new ATP cannot be easily made when you are really run down. Recovery takes days!

When mitochondria function well, as the person rests following exertion, lactic acid is quickly converted back to glucose (via-pyruvate) and the lactic burn disappears. But this is an energy requiring process! Glucose to lactic acid produces two molecules of ATP for the body to use, but the reverse process requires six molecules of ATP. If there is no ATP available, and this is of course what happens as mitochondria fail, then the lactic acid may persist for many minutes, or indeed hours causing great pain. (for the biochemists, this reverse process takes place in the liver and is called the Cori cycle).”