Tricarboxylic acid cycle (“TCA cycle” also known as a citric acid cycle or Krebs cycle) plays a number of roles in metabolism. This is the final route where the oxidative metabolism of carbohydrates, amino acids and fatty acids, their carbon skeleton is converted to CO2. This oxidation provides energy for most ATP production in animals, including humans. The cycle is found entirely in mitochondria and, therefore, is in close proximity to the electron transport reaction, which oxidizes the coenzymes produced by the cycle. The TCA cycle is an aerobic pathway, as O2 is required as the final electron acceptor. Most of the body’s metabolic pathways are found on the TCA cycle. Some produce batches of amino acids such as metabolism and are called anaplerotic reactions. The citric acid cycle also participates in several important synthetic reactions. For example, the cycle of glucose formation works from the carbon skeleton of some amino acids, and it provides the building blocks for the synthesis of some amino acids and heme. Therefore, this cycle should not be viewed as a closed circle, but instead will be added as a traffic circle and depart as needed.
Reaction of TCA Cycle.
In the TCA cycle, the oxaloacetate is first condensed with the acetyl group of acetyl coenzyme A (COA) and then regenerates after the cycle is completed. Thus, the admission of an Estelle COA during one of the TCA cycles does not lead to net production or consumption of intermediates.
Oxidative Decarboxylation of Pyruvate.
Pyruvate, the last product of aerobic glycolysis, into the mitochondron before entering the TCA cycle. This is accomplished through a specific pyruvate transporter that helps the pyruvate to cross the inner mitochondrial membrane. Once in the matrix, the pyruvate is converted to the acetyl CoA via the pyruvate hydrogenase complex, which is a multienzyme complex. Strictly speaking, the pyruvate dehydrogenase complex is not an appropriate part of the TCA cycle, but an important source of acetyl CoA is the two-carbon substrate for the cycle.
The pyruvate dehydrogenase complex is a combination of three enzymes, multimolecular dehydrogenase (also known as E, also a decarboxylase), dihydrolipoly transacetylase (E2), and dihydrolipoly dehydrogenase (E3). Each is contained in multiple copies, and each produces a portion of the overall reaction. Their physical associations combine reactions in the proper order without the release of intermediates. In addition to the enzymes that participate in the conversion of pyruvate to acetyl CoA, this complex also contains two strictly binding regulatory enzymes, pyruvate dehydrogenase kinase, and pyruvate dehydrogenase Phosphatase.
The pyruvate dehydrogenase complex contains five coenzymes that act as carriers or oxidants for the intermediates of reactive E1 require thiamine pyrophosphate, E2 requires lipoic acid and CoA, and E3 Requires FAD and NAD+. [Note: Thiamine or niacin deficiencies can cause serious nervous system problems. This is because if pyruvate dehydrogenase is inactive, brain cells are unable to produce the appropriate ATP (via the TCA cycle) for proper function.
Regulation of the pyruvate dehydrogenase complex.
Two Regulatory enzymes that in turn activate and deactivate E1. Cyclic AMP-free PDH kinase phosphorylates and, thus, inhibits E1, while PDH activates phosphatase E1. Kinase is fully mobilized by ATP, acetyl CoA, and NADH. Therefore, in the presence of these high energy signals, the pyruvate dehydrogenase complex is off. Acetyl CoA and NADH inhibit the dephosphorylated form of E1 separately. Pyruvate is a potent inhibitor of pyrite dehydrogenase kinase. Therefore, if pyruvate concentration is elevated, it will be more dynamic. Calcium is a potent activator of PDH, a phosphatase activator that activates E. [Note: This is especially important in skeletal muscle, where the release of Ca2+ during contraction stimulates the pyruvate dehydrogenase complex and thus energy production.
Energy Produced by The TCA Cycle.
The two carbon atoms enter the cycle as Acetyl CoA and move as CO2. This cycle does not include pure use or production of oxaloacetate or any other intermediate. During one turn of the cycle, four pairs of electrons move: three pairs of electrons reduce three NAD+ to NADH and one pair FAD to FADH2. The oxidation of one NADH through the electron transport chain produces about three ATP, while the oxidation of FADH2 produces about two ATP. The total production of ATP from the oxidation of acetyl CoA summarizes the reaction of the TCA cycle.
Regulation of TCA Cycle.
Unlike glycolysis, which is mainly regulated by phosphofructokinase, the TCA cycle is regulated by several enzyme activity rules. The most important of these regulated enzymes are those that stimulate the reaction with highly negative ΔG∘ citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase complex. Reducing the required requirements for oxidative phosphorylation was developed by the Pyruvate hydrogenase complex and the TCA cycle, and both processes have been eliminated in response to the increase in ADP.