Energy metabolism is a process that is essential in the maintenance of life and has obvious roles with regards to sporting/exercise performance. The body can produce energy both aerobically and anaerobically and the regulatory mechanisms underlying these pathways of energy modulation are complex. Under aerobic conditions the Krebs cycle is crucial for energy production, the hydrogen’s removed during the cycle are transferred to the electron transport chain and the energy released during electron transport is utilised in the formation of ATP. Oxygen’s role in aerobic respiration is to act as the final hydrogen/electron accepter to form water. If this is not present the whole aerobic pathway cannot occur and so the body will rely on energy produced anaerobically. The question instantly raised is to whether oxygen is ever in short supply, does it become a limiting factor for energy metabolism? Or are other factors limiting? Can increasing or maintaining NAD+ concentrations sustain the action of the Krebs cycle and bring about the continuation of oxidative phosphorylation and therefore reducing build up of lactate as a consequence? If this hypothesis were to be true then this could have advantageous implications in sporting performance.
Arterial oxygen content does not decrease at exercise intensities <75% of VO 2 max. VO2max is a measure of the ability of working muscles to oxidise metabolic substrates, with eventually a plateau in oxygen uptake occurring despite increases in work rate therefore achieving maximal oxygen uptake. This capacity is exceeded before circulating delivery of oxygen is limiting. This is a significant, as it suggests that oxygen delivery is only limiting at VO 2 max where beyond this point oxygen uptake and delivery will become limiting. With regards to the majority of sporting events, exercise is carried out sub maximally for the athlete and so oxygen supply will not be limiting. An early experiment concluded that it seems unwarranted at present to ascribe alterations in body lactate to oxygen deficiency. This paper states that oxygen saturations exceeded 96% at every intensity set for the experiment (mild or severe). The phenomenon of the O 2 debt formation is a manifestation of the need for oxygen by the body tissues during exercise which is not met at the time. This occurs despite the rate of delivery of oxygen to the tissues being greater per minute than normal. This is more supportive evidence that oxygen is not a limiting factor and is in fact transported efficiently to meet the demand, at least at exercise intensities up to 85-90% VO 2 max. Hence, why other metabolic factors appear to be limiting to such a degree that the cessation of aerobic respiration occurs. Blood flow redistribution is important to help compensate for the limits on O 2 delivery and uptake set by maximal cardiac output and O 2 extraction. The oxyhaemoglobin dissociation curve demonstrates the extreme efficiency of haemoglobin at combing with O 2 in the lungs and unloading at tissues, this can be up to 90% of the O 2 carried by haemoglobin during intense exercise. The myoglobin in the muscles functions as an oxygen store and transporter. With regards to the respiratory system it has been identified that it only becomes limiting in untrained individuals with the endurance of respiratory muscles markedly improving in trained individuals.
Figure 1.Flow diagram representing the stages in energy metabolism and how NAD affects each of these stages. NAD is required largely during the Krebs cycle but also is required during glycolysis and for the conversion of pyruvate at the end of glycolysis for its entry into the Krebs cycle
When the oxidative potential of a cell has diminished pyruvate can be converted to lactic acid by lactate dehydrogenase. This is important as energy can still be produced through the continuation of glycolysis. The rates of the oxidation for energy metabolism are not affected until NAD+ is affected. If oxidative energy metabolism is so greatly impacted by NAD+, knowing that even during intense exercise oxygen is not in short supply nor are the delivery mechanisms efficiency, can increasing NAD+ concentration allow aerobic metabolism to continue? [Lactate] = [pyruvate] x k[DPNH2]/[DPN], the equation suggests, on a theoretical basis, that all instances of lactate production by tissues are influenced by the ratio of NAD+ and NADH (DPN or Diphosphopyridine nucleotide is another name for NAD) thus leading one to assume that lactate production can be manipulated by altering the ratio.
It has been stated that conclusions about tissue oxygen supply should not be drawn from determining lactate alone, suggesting the interaction between the anaerobic and aerobic energy systems are intricate. For example epinephrine has been found to increase lactate in muscle which is not due to diminished blood flow or blood arteriovenous oxygen difference. Lactate produced during high intensity endurance activities appear to be occurring when the maximum rate of fat oxidation is inadequate to meet the demands of muscle contracting. This causes intracellular signalling events to occur which ultimately lead to the rate of pyruvate delivery to the mitochondria progressively exceeding the ability of the mitochondria to convert and transfer it into the Krebs cycle causing accelerated generation of lactic acid. It has been argued that lactate formation will occur when NADH and pyruvate are available to lactate dehydrogenase regardless of how much O2 is present. Lactate dehydrogenase can convert lactate back to pyruvate for further utilisation in the Krebs cycle, the reaction does make use of NAD+. The problem becomes one of fuel availability when exercise extends beyond approximately two hours but events lasting 15-30minutes (e. g. 5km and 10km running) the anaerobic contribution can be 10-20% of total ATP turnover. Total ATP turnover during endurance performance reflects the interplay of aerobic and anaerobic metabolism with lactate generation functioning to maintain the NAD+ needed for continuation of glycolysis. If more NAD+ could be supplied or synthesised could lactate be converted back to pyruvate for use in the Krebs cycle and could aerobic metabolism be sustained for longer with reduced lactate build up? Lactate is produced regardless of how much O2 is present as long as pyruvate is available but with increased NAD+ pyruvate would be converted to Acetyl CoA for its entry into the Krebs cycle. The exact mechanisms by which lactate plays a role in fatigue has remained elusive but it’s clear it has some debilitating role as endurance trained individuals produce less. Although only assumptions presently, the implications that NAD+ could have on prolonging aerobic metabolism on exercise performance could be incredible, especially when considering the small margins between winning and losing in many sporting environments.
The human body will adapt in a variety of manners to physical training, these can effect both major systems/organs and more microscopic changes cellularly. These adaptations occur as a result of prolonged exposure to particular situations in an attempt to become a more efficient system. There is evidence that rats see an increase in mitochondria along with certain enzyme activities per gram/muscle (NADH dehydrogenase and NADH cytochrome c reductase), increasing approximately two fold in response to training. This results in a increased capacity of the electron transport chain which was associated with a concomitant rise in the capacity to generate ATP via oxidative phosphorylation. A similar study conducted on rabbits using electrical stimulation of the muscle draws the same conclusion with an increased volume of mitochondria. The exercise induced adaptation of increased mitochondria content appear to be essential for trained muscle to exhibit an increased O2 flux capacity, illustrating the significance of mitochondrial adaptations. Trained endurance runners saw at least a 2. 5 times higher activity value in succinate dehydrogenase than untrained individuals, implying that enzyme activity of the Krebs cycle increases and adapts. It is known that beta oxidation of fatty acids involves FAD and NAD, so it would seem feasible to suggest that increasing NAD concentration/synthesis could help increase or maintain utilisation of fat in doing so sparing glucose.
The Krebs cycle itself is an elaborate chain of intermediate compounds, enzymes and reactions. The cycle is responsible for approximately 67% of all generated reducing equivalents per molecule of glucose, highlighting the importance of Krebs cycle flux for oxidative phosphorylation. An increase in the total concentration of the Krebs cycle intermediates is also necessary to augment and maintain Krebs cycle flux during exercise. NAD+ plays a central role throughout the cycling of reactions and so with the suggestion that Krebs cycle intermediates increase during exercise training, increasing NAD+ biosynthesis and therefore concentration/pool size could have beneficial effects on exercise performance. Research has been carried out on maximal one leg exercise and the results show that as maximal oxygen uptake increased to the muscle the maximal enzyme activity of citrate synthase, α-ketoglutarate dehydrogenase and succinate dehydrogenase increased to match demand. α-ketoglutarate dehydrogenase average maximal activity is almost the same as the average flux through the Krebs cycle. This indicates that the enzyme activity is fully activated during maximal exercise (one leg exercise) and is one factor limiting the flux through the Krebs cycle. Enzyme activity within t
