Complex X (Cont'd)

Complex X is the substance that is formed when skeletal muscles create energy by breaking down glucose, in the form of muscle glycogen, in the cytoplasm of the cell. When the energy is created in the cytoplasm, or body, of the cell, no oxygen is utilized as part of the chemical process, so it is called anaerobic (“without oxygen”) metabolism.  The other, more familiar, type of metabolism is known as aerobic (“with oxygen”).  Aerobic metabolism occurs in mitochondria, which are specialized energy-producing organelles that are found in all muscle cells. 


Anaerobic metabolism generates energy quickly, and thus anaerobic metabolism provides most of the energy whenever the body needs to move quickly or explosively.  But it is considered inefficient, because it converts only a small amount of the glucose into energy. Most of the glucose that comprises the glycogen is converted into pyruvate.  That pyruvate, which is the primary byproduct, or metabolite, of the anaerobic process, is then available to be used as fuel by mitochondria in the aerobic metabolic process.   Although it is generally believed that glucose is a primary source of fuel utilized by mitochondria, glucose molecules are too large to be metabolized by mitochondria – they must first be broken down through the anaerobic glycolytic process. 


Historically, based upon studies of glycolysis in yeast and similar organisms in the laboratory, it was observed that when oxygen was present (aerobic), glycolysis was slow and acid products did not accumulate. When oxygen was removed (anaerobic), glycolysis was rapid, but lactic acid would accumulate.  These observations led to some gross misperceptions that still persist in many quarters.  It was believed that anaerobic metabolism would occur only when insufficient oxygen was available to support the oxidative or aerobic metabolic process.  Anaerobic exercise would quickly lead to fatigue because lactic acid would build up and the muscles would get sore.  The athlete would have to pause or rest to allow the body to recover from the “oxygen deficit” before being able to continue.


The modern theory, known as the “lactate shuttle hypothesis,” is that lactate is formed and utilized continuously under fully aerobic conditions.   The first steps in the glycolytic process are always anaerobic.  That does not mean that oxygen is not present in the cell, it just means that the process takes place in the cytoplasm of the cell, and that oxygen is not part of the chemical equation.   In glycolysis, glucose/glycogen is broken down to pyruvate.  Pyruvate can enter the mitochondria and be processed aerobically.  However, if it does not enter the mitochondria immediately, the pyruvate will be converted into lactate due to an enzyme called lactate dehydrogenase (LDH).  Since LDH is always present in skeletal muscle cells and acts almost immediately, excess pyruvate always converts into lactic acid.  And then the lactic acid almost immediately converts into lactate. 


The net formation of lactate or pyruvate, then, depends on relative glycolytic and mitochondrial activities, and not on the presence of oxygen.  Even at rest, under fully aerobic conditions, in order for skeletal muscles to use glucose as fuel, that glucose must be broken down by anaerobic glycolysis, and that glycolysis inevitably leads to lactate production.  In addition to lactate, there are other byproducts, or metabolites, of anaerobic glycolysis.  These other metabolites, together with lactate, constitute Complex X.


When more lactate is produced than the amount that can be processed by the mitochondria, the lactate/Complex X will leave the cell and either be used as fuel by other cells in the immediate vicinity, or enter the bloodstream.   Since the anaerobic process works very quickly, and the aerobic process works relatively slowly, intense exercise results in the creation of excess lactate/Complex X. When one is doing intense exercise (sprinting, jumping or lifting weights, for example), substantially all of the lactate/Complex X that is formed passes out of the cell and into the bloodstream.  


Once the lactate is taken up by the bloodstream, it is used in other organs, such as the heart, brain, liver and kidneys.   During intensive exercise, lactate is the preferred fuel for not just for skeletal muscles, but also all other organs.  In this context, the term “preferred” means that the organs will use the lactate first, even if alternative fuel sources, such as blood glucose and lipids, are available.   That use of lactate (and the other components of Complex X) by the remote organs induces mitochondrial biogenesis in those organs.  In addition, the increased levels of Complex X in the bloodstream trigger the release of the other substances that facilitate the growth and rejuvenation of those organs, and the lactate fuels that Growth Process.


Lactate is the primary component of Complex X.   The Hypothesis posits that the other metabolites of anaerobic glycolysis also play a critical role.  These other metabolites are small molecules that are produced as byproducts of the anaerobic process.  One recent study characterized the metabolites from anaerobic metabolism as being comprised primarily “of scaffolds of amino acids, pyrimidine and purine nucleotides, saccharides, glycosyl phosphates and folic acids, which are nearly all primary metabolites and are essential for core cellular functions.”  In addition to being associated with essential cellular functions such as growth, development and energy production, primary metabolites frequently act as signaling molecules.  


One of the key roles of Complex X is to act as the master gatekeeper and coordinator for the Growth Process – a signaling function.  Lactate is an excellent fuel source, and lactate has long been recognized as being associated with the signaling process throughout the body.   But the metabolites other than lactate appear to be better suited for this signaling function.  The Hypothesis posits that lactate is the means by which the other metabolites that comprise Complex X are carried into the bloodstream and delivered to other parts of the body.  It’s Complex X as a whole, rather than the lactate alone, that performs the critical signaling functions.