What happens in the citric acid cycle and why is it critically important for all life?
The Citric Acid Cycle, also known as the Krebs Cycle, is an important series of biochemical reactions that are intrinsic to cellular respiration and the generation of energy from oxygen and glucose in aerobic organisms. Although humans can generate energy anaerobically, they cannot do so for long periods and oxygen is essential for life because it fuels the Citric Acid Cycle. Without this cycle, there would be no available energy to maintain our vital processes.
The citric acid cycle takes place within the mitochondria of the body cells and begins with glycolysis, during which glucose is converted to two molecules of pyruvate with the aid of nicotinamide-adenine dinucleotide (NAD): no oxygen is required for this step.
In shorthand, that is Glucose + 2NAD+ + 2P + 2ADP = 2Pyruvate + 2NADH + 2H+ + 2ATP.
The pyruvate can then undergo aerobic or anaerobic respiration to generate energy. The citric acid cycle is the aerobic route, and significantly more efficient that the alternative fermentation.
The two pyruvate molecules are then oxidized to two of Acetyl CoA with the release of carbon dioxide. The two acetyl groups of the Acetyl CoA are donated to Oxaloacetate in the presence of water to form Citrate.
Citrate then undergoes a number of chemical reactions to arrive back at Oxaloacetate again and the cycle starts all over again by reacting with more Acetyl CoA from Pyruvate and oxygen to form Citrate again. During the cycle more ATP is produced and electrons and other species are sent into the Electron Transfer Chain where most energy is generated.
The citric acid cycle takes place within the mitochondria, structures that are contained in each of your body cells. Also within these mitochondria are a series of membranes that are very important in the generation of energy.
The major energy produced in your body cells comes from the Electron Transport Chain, a series of chemical reactions between an electron donor and an electron acceptor. Such reactions drive the transport of hydrogen ions (H+) across the membranes in the mitochondria.
The electron donors are species such as NADH, FADH2 and succinate and the electron acceptors are oxygen molecules. Hence the importance of oxygen in the process of aerobic respiration. The H+ ions are driven across the membranes and result in the conversion of ADP to ATP energy. In essence, the hydrogen atoms and electrons take part in a progressive chain of redox reactions, and at the end react with oxygen molecules and change it to water.
Ultimately, through the whole chain and cycles of: Glucose to pyruvate (glycolysis) Pyruvate to Acetyl CoA + CO2 (oxidation) Acetyl CoA to Citrate and the entire citric acid Cycle (reduction and oxidation) citric acid Cycle products to the Electron Transfer Chain Electron Transfer Chain to Water and ATP (redox) Final oxidation of hydrogen atoms to water.
In shorthand: Glucose + Oxygen + 30ADP = Carbon Dioxide + Water + 30ATP
The entire process of glycolysis, oxidation, citric acid Cycle and Electron Transport Chain is powered by a series of enzymes and a small amount of ATP energy.
Glucose and oxygen are used up as the raw materials and ATP energy molecules are the product.
Were it not for the citric acid Cycle you would not be able to generate energy efficiently. The energy comes from the carbohydrate content of your food, which can be derived from sugars, starches as well as fats, and even from proteins which contain a carbohydrate tail as well.
Your body will preferentially use the carbohydrates in your diet as a source of glucose, then turns towards fats in food or the body, and finally to proteins.
Were it not for the citric acid cycle, your body could not use the glucose as described above to generate energy. The only option open to it would be anaerobic respiration, or energy production in the absence of oxygen. ATP is still generated, but much less efficiently.
Anaerobic respiration is basically respiration without oxygen. If there was no citric acid cycle, then this is the only way your body would have to create energy.
Some organisms don't use oxygen for the the citric acid cycle, but another substrate like nitrate or sulfate. Because the Reduction Potential of these species is much lower than that of oxygen, the amount of ATP energy produced is also much lower.
In absence of oxygen, your body tries to compensate by producing even more pyruvate and the excess is removed through lactic acid fermentation. Although this also generates ATP energy enough for short-term use, it leads ultimately to lactic acidosis and a reduction in pH, causing pain and vomiting.
Ultimately, if oxygen is not forthcoming, the brain runs short of the energy needed for it to work and you die. There is insufficient ATP generated from anaerobic respiration to maintain human life.
The citric acid cycle is of critical importance for the production of energy: not just the energy to enable you to run fast, but to enable your metabolic processes to continue. It is needed for both aerobic and anaerobic respiration, and while lactic acid fermentation can be used by your muscle cells as a brief but effective means of generating short-term energy, it is insufficient to maintain the needs of your metabolism.
Without the citric acid cycle, mammalian and most other animal life would not be viable and the world would be populated by anaerobic bacteria.
Apart from the molecules mentioned above, other micronutrients are important too for a citric cycle to functionn, those being B-vitamins and co-enzyme Q10.
One of the key lynch-pins in the mitochondrial energy pathways is a substance called NAD (nicotinamide adenine dinucleotide). It is present in 2 forms, NAD+ (the oxidized form) and NADH (the reduced form). What is becoming clear is that the NAD+ to NADH ratio plays powerful role in controlling how much energy the mitochondria and produce. Higher NAD+ levels are thought to have a stimulatory effect on beneficial genes and energy production while a high NADH concentration is thought to inhibit beneficial genes and limit energy production. This is now referred to as the NAD+/NADH ratio theory of aging and chronic disease.
However, despite this fact there is research showing that NADH supplementation has health benefits, probably because the body converts it back to the more beneficial NAD+ molecule. Clinical trials of NADH have found that it can significantly improve conditions such as Parkinson’s disease because it can support the synthesis of dopamine. It was also found to improve dementia in Alzheimer’s disease. NADH’s role in energy production makes it potentially useful for dealing with fatigue. Clinical trials found that NADH was effective against the symptoms of chronic fatigue syndrome. In animal studies, it was found to lower blood pressure, total cholesterol and levels of LDL “bad” cholesterol.
One of the ways to increase that very same NAD+/NADH ratio is to supplement with a thermally stable form of oxaloacetic acid, called benaGene. Apparently it is able to mimic the changes in the expression of over 350 genes in a similar fashion to caloric restriction. Both have in common that the ratio of NAD+/NADH increases.
What has scientists and anti-aging enthusiasts so excited is that animal studies have shown that life span was extended by 30% after supplementing with BenaGene. It also promoted a genetic profile similar to calorically restricted animals. Clinical trials have confirmed both reduction in glucose levels and an improved uptake of glucose without negative side effects. This action alone has a tremendous beneficial effect of numerous disease processes such as diabetes, Alzheimer’s disease, cardiovascular disease and even cancer.
Calorie restriction has numerous health benefits including increased longevity and disease prevention. The mechanism of calorically restricted diet is that it increases the NAD+ to NADH ratio in the mitochondria, optimizing energy production and creating an optimal cellular environment which translates into the expression of beneficial genes. Supplementation with a specific stabilized form of oxaloacetate called BenaGene has shown positive effects that can mimic the effect of a calorically restricted diet. This can translate into clinical applications for almost every chronic disease.
BenaGene is the world's first novel and natural citric acid cycle intermediate compound that is specifically formulated to be highly stable and bio-available so that a one-a-day dosage is all that is required, offering the potential of life and health extension.
In closing, we also want to mention how recently a constituent of NAD, nicotinamide riboside has become very popular too. Nicotinamide is the direct precursor to NAD+ (nicotinamide-adenine dinucleotide).
Just like oxaloacetic acid, NAD+ is a critical substrate for several enzymes, including the sirtuin enzymes, that play an important role in healthy aging and healthy energy metabolism, causing easier fat loss.