A keenly debated topic is what limits the maximum rate of oxidative phosphorylation by an individual. Is it limited by oxygen transport from to air to the muscle (i.e. transport limited?). Or is the limitation based on metabolic factors (i.e. electron transport chain; read below)?
Endurance training improves the electron transport chain and tricarboxylic acid cycle (TCA cycle) three to five times more than the ability to transport oxygen. This means that a fit individuals oxygen transport is the key limiter for training (i.e. why blood doping is so widely used!).
For unfit individuals, oxygen transport is plentiful but metabolism is the key limiter. At high intensity or long events the body is unable to keep up with the demands of carbohydrate and must turn to beta oxidation for fuel. This slows down the production of Aceyl CoA (responsible for 2/3s of ATP production) and thus this is why athletes slow down as energy stores are low.
The “Gs”
Glucose – A simple sugar used in the body for functioning.
Glycolysis- A catabolic pathway that breaks down glucose 6-phosphate derived from glucose or glycogen into pyruvate and in the process generates ATP (energy)
Glycogenolysis- Glycogen stored in the liver or muscles is convered to glucose-1 phosphate and then into glucose-6 phosphate. It is regulated by hormones (pancreas) glucagon and epinephrine (adrenal glands).
Glucogenesis – Formation of glycogen from glucose. Glycogen is created depending on the demand for glucose and ATP (energy). If both are present in high amounts, then the excess of insulin (hormones) promotes the glucose conversion into glycogen for storage in liver and muscle cells.
Gluconeogenesis – the process of synthesizing glucose from non-carbohydrate sources (lactic acid, glycerol from fat and some amino acids). Gluconeogenesis takes place in the liver to constantly provide energy to the system. Pyruvate is the first substrate of the gluconeogenic pathway, converted from lactate by the Cori cycle to be used as glucose.
Cori CycleCori Cycle – The importance is to prevent lactic acidosis in the muscle under anaerobic conditions. The cycle is also important in producing ATP, an energy source, during muscle activity.
Tri-carboxylic-cycle (TCA Cycle) or the Citric Acid Cycle – A sequence of reactions taking place in mitochondria where acetyl units attached to CoA are degraded to CO2, and the electrons produced are transfered to the coenzymes NAD+ (used in redox reactions) and FAD (oxidation-reduction coenzyme).
Electron Transport Chain (ETC) - Free energy from the TCA cycle is run through the ETC and phosphorylates ADP with Pi to make ATP (energy).
Oxidative Phosphorylation(aerobic metabolism) – Generally it is the formation of ATP from ADP and Pi. It encompasses the respiratory chain comprised of the TCA and ETC which takes place in the mitochondrion.
Fermentation- process of deriving energy from oxidative organic compounds.
Lactate Transport
Lactate is being continuoulsy produced from pyruvate via the enzyme lactate dehydrogenase (LDH) in a process of fermination. Formation of lactate by a muscle means that pyruvate is being produced in the cytosol by the glycolytic pathway. Lactate transport across the muscle sarcolemma can occur in both directions. In the absence of oxygen (high intensity), pyruvate is formed by glycolysis and can either be reduced to lactate or enter a nearby mitochondrion and be oxidized to acetyl CoA; thus the direction is out of the cell and go through the Cori cycle. At lower levels of exercise (i.e. VO2 max <60%) some lactate is being produced but the concentration in muscle and blood isn’t significant, thus pyruvate will be oxidized in the mitochondrion.
When demand for energy is high, lactate is produced faster than the ability of the tissues to remove it, so lactate concentration begins to rise. Lactate can be removed by oxidation to pyruvate by well-oxygenated muscle cells. This is done via the TCA cycle and ETC.
Training can help improve that lactate buffer. Working at intensities at the ‘lactate threshold’ can help train the body to deal with the toxic build of dissociated hydrogen ions (acid). Improving the aerobic capacity, so more fat is being burned, is the key platform for endurance athletes who wish to perform better.
Summary
So to recap, glycogen is broken down by a process known as glycogenolysis which releases glucose in the form of glucose-6-phosphate. This is fed into glycolysiswhich provides ATP to the muscle cells as energy. During exercise, ATP is constantly being used and replenished. When performing aerobic exercise, the energy comes from feeding pyruvate into the TCA cycle. When exercise becomes very intense and the supply of oxygen is insufficient (anaerobic), lactate dehydrogenase converts pyruvate to lactate. Lactate is taken up by the liver and this initiates gluconeogenesis which reverses glycolysis and fermentation. This converts lactate first into pyruvate and finally back to glucose. If muscle activity stops, glucose is used to replenish the supplies of glycogen through glycogenesis.
Overall, the glycolysis part of the cycle produces 2 ATP molecules at a cost of 6 ATP molecules consumed in the gluconeogenesis part. Each iteration of the cycle must be maintained by a net consumption of 4 ATP molecules. As a result, the cycle cannot be sustained indefinitely. The intensive consumption of ATP molecules indicates that the Cori cycle shifts the metabolic burden from the muscles to the liver.
