Fundamentals of Human Nutrition/Citric Acid cycle
12.4 Citric Acid Cycle
The citric acid cycle, also called the Krebs cycle, is the final stage of the oxidation of glucose. The carbon atoms enter the cycle as acetyl-CoA formed in the previous step (decarboxylation of pyruvate) and are oxidized in mitochondrial eight reactions to form various compounds such as CO2 and various hydrogens which are then captured by the NAD and FAD, produzind to three molecules of NADH and FADH2, and ATP release. These molecules formed during the Krebs cycle (NADH and FADH2) are acceptors H (receptors) intermediates of hydrogen which bind to protons (H +), released during the stages of metabolism of glucose, giving them for oxygen, which is acceptor (receiver) end of hydrogens.
After the Krebs cycle, molecules of NADH and FADH2 produced during all stages of metabolism of glucose, are transferred to the mitochondrial cristae, so that the electrons present in these molecules are transferred to oxygen, are the final electron receptor. This process is called oxidative phosphorylation. The electrons are passed from molecule to molecule in cytochromes present in mitochondrial cristae. When the electron "jumps" from one cytochrome to another until you reach the end acceptor (oxygen), is the release of energy, which is converted into ATP.
The general formula of complete metabolization of glucose consists:
Glucose + 6O2 → 6CO2 + 6H2O + 38ATP
After all the glucose metabolism (glycolysis by oxidative phosphorylation) for the formation of carbon dioxide, water and 38 ATP molecules. This process is called cellular respiration, therefore the cell receives oxygen and sugar (in this case glucose) and releases energy in the form of ATP, carbon dioxide and water.
Citric acid cycle is a catabolic pathway for fats, carbohydrates, and amino acids. It takes place in the inner compartment of the mitochondria, which is an important contribution for the final step in energy metabolism, the electron transport chain. When cells need energy, acetyl CoA (a 2 carbon compound), accesses the citric acid cycle. It is a continuous path since oxaloacetate (a 4 carbon compound) is needed in the first stage and is then synthesized in the final stage. However, the citric acid cycle does not regenerate acetyl CoA. Oxaloacetate has an important role in the citric acid cycle; enough has to be present for acetyl CoA to start its course. Whitney and Rolfes (2015). A diet with sufficient carbohydrate ensures an ample supply of oxaloacetate, because in the previous steps of glycolysis, glucose produces pyruvate.
Oxaloacetate is the first compound to enter the Krebs cycle. Oxaloacetate first picks up acetyl CoA, drops off two carbons as carbon dioxide and then returns as before to pick up another acetyl CoA. As compounds in the citric acid cycle lose a carbon to carbon dioxide, hydrogen atoms containing electrons are transported by coenzymes made from vitamin B (riboflavin and niacin) towards the electron transport chain. Every run of the citric acid cycle yields a total of eight electrons. Whitney and Rolfes (2015).
There are few molecules that can inhibit the citric acid cycle: fluoroacetate, arsenite, and malonate. Fluoroacetate combines with CoA and forms fluoroacetyl-CoA. Fluoroacetyl-CoA then combines with oxaloacetate to form fluorocitrate which hinders the function of aconitase, resulting in the accumulation of citrate. Arsenite inhibits alpha-ketoglutarate dehydrogenase (the enzyme complex that helps alpha-ketoglutarate become succinyl CoA) and malonate inhibits succinate dehydrogenase (the enzyme complex in the reaction of succinate to fumarate). Akram, M. (2014).
The citric acid cycle plays an important metabolic role in our bodies. The acetyl CoA produced from glucose oxidation regulates the oxidation of fatty acids. After the deamination of many amino acids, it results in intermediate compounds of the citric acid cycle. First, fatty acids are oxidized to acetyl CoA that is then oxidized in the TCA cycle. Jin, Sherry, and Malloy (2013). Krebs cycle is one of the main catabolic pathways that living cells apply to oxidize simple sugar molecule obtained from food to water and carbon dioxide. In conjunction with supplying energy, this cycle also provides the intermediates needed for the synthesis of compounds like glucose, amino acids, etc. The citric acid cycle is considered amphibolic, due to its different metabolic roles aside from oxidation. It takes place in other pathways such as gluconeogenesis, deamination, transamination, and the synthesis of fatty acids. Akram, M. (2014).