Oxidative decarboxylation is a component of cellular respiration and occurs in the mitochondria of the cell. The end product of oxidative decarboxylation, acetyl-coA, is then further processed in the citrate cycle.
What is oxidative decarboxylation?
Oxidative decarboxylation is a component of cellular respiration and occurs in the mitochondria of the cell. Mitochondria are cell organelles found in almost all cells with a nucleus. They are also called power plants of the cell because they produce the molecule ATP (adenosine triphosphate). ATP is the most important energy carrier in the human body and is obtained by aerobic respiration. Aerobic respiration is also titled cellular respiration or internal respiration. Cellular respiration is divided into four steps. At the beginning, glycolysis takes place. This is followed by oxidative decarboxylation, then the citrate cycle, and finally end oxidation (respiratory chain). Oxidative decarboxylation takes place in the so-called matrix of the mitochondria. In short, pyruvate, which mostly comes from glycolysis, is converted to acetyl-CoA here. For this purpose, pyruvate, an acid anion of pyruvic acid, attaches to thiamine pyrophosphate (TPP). TPP is formed from vitamin B1. Subsequently, the carboxyl group of pyruvate is split off as carbon dioxide (CO2). This process is called decarboxylation. Hydroxyethyl-TPP is formed in the process. This hydroxyethyl-TPP is then catalyzed by the so-called pyruvate dehydrogenase component, a subunit of the pyruvate dehydrogenase enzyme complex. The acetyl group remaining thereafter is transferred to conenzyme A by catalysis through dihydrolipoyl transacetylase. This produces acetyl-CoA, which is required in the subsequent citrate cycle. A multienzyme complex consisting of the enzymes decarboxylase, oxidoreductase, and dehydrogenase is required for this reaction to proceed undisturbed.
Function and task
Oxidative decarboxylation is an indispensable component of internal respiration and thus, like glycolysis, the citrate cycle, and end oxidation in the respiratory chain, serves to produce energy in cells. To do this, the cells take up glucose and break it down as part of glycolysis. In ten steps, two pyruvates are obtained from one glucose molecule. These are a prerequisite for oxidative decarboxylation. Although ATP molecules are already obtained during glycolysis and oxidative decarboxylation, they are much less than during the citrate cycle that now follows. Basically, an oxyhydrogen reaction takes place in the cells during the citrate cycle. Hydrogen and oxygen react with each other and energy in the form of ATP is produced with the release of carbon dioxide and water. About ten ATP molecules can be synthesized per round of a citrate cycle. As a universal energy carrier, ATP is essential for human life. The energy molecule is the prerequisite for all reactions in the human body. Nerve impulses, muscle movements, the production of hormones, all these processes require ATP. Thus, the body forms about 65 kg of ATP per day to meet its energy needs. In principle, ATP can also be obtained without oxygen and thus without oxidative decarboxylation. However, this anaerobic-lactacid metabolism is much less productive than aerobic metabolism and also leads to the formation of lactic acid. During heavy and prolonged exercise, this can lead to hyperacidity and overfatigue of the affected muscle.
Diseases and complaints
A disease caused by a disturbance in oxidative decarboxylation is maple syrup disease. Here, the disorder is not in the breakdown of glucose but in the breakdown of the amino acids leucine, isoleucine, and valine. The disease is inherited and often manifests itself immediately after birth. Affected newborns suffer from vomiting, respiratory disorders up to respiratory arrest, lethargy or coma. Shrill cries, convulsions and an excessively high blood sugar level are also typical. The defective breakdown of amino acids results in the so-called 2-keto-3-methylvaleric acid. This gives the children’s urine and sweat the characteristic smell of maple syrup that has helped give the disease its name. If left untreated, the disease quickly leads to death. In oxidative decarboxylation, as already indicated, vitamin B1 (thiamine) plays an important role. Without thiamine, the decarboxylation of pyruvate to form acetyl-CoA is not possible.A severe B1 deficiency is the cause of beriberi disease. This used to occur mainly on plantations or in prisons in East Asia, where people mainly fed on hulled and polished rice, because vitamin B1 is only found in the husks of rice grains. Due to the deficiency of thiamine and the associated inhibition of oxidative decarboxylation, beriberi disease primarily causes disorders in tissues that have a high energy turnover. These include skeletal muscle, cardiac muscle, and the nervous system. The disease manifests itself as apathy, nerve paralysis, enlargement of the heart, heart failure and edema. Another disorder in which oxidative decarboxylation is impaired is glutaraciduria type I. This is a rather rare hereditary disease. Affected individuals are initially without symptoms for a long time. The first symptoms then appear in the course of a catabolic crisis. Severe movement disorders occur. The trunk is unstable. Accompanying fever may occur. The early symptom of glutaraciduria type I is macrocephaly, i.e. a skull that is larger than average. Once the first symptoms appear, the disease progresses rapidly. However, children diagnosed early have a promising prognosis and usually develop well with treatment. However, the disease is often misdiagnosed as encephalitis, an inflammation of the brain. The diagnosis of glutaraciduria type I can be made quite easily by urinalysis. However, the disease is rare, so symptoms are often misinterpreted and testing for the disease is not initially done.
