Pyruvate decarboxylation

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Pyruvate dehydrogenase complex reaction Pyruvate dehydrogenase complex reaction.svg
Pyruvate dehydrogenase complex reaction

Pyruvate decarboxylation or pyruvate oxidation, also known as the link reaction (or oxidative decarboxylation of pyruvate [1] ), is the conversion of pyruvate into acetyl-CoA by the enzyme complex pyruvate dehydrogenase complex. [2] [3]

The reaction may be simplified as:

Pyruvate + NAD+ + CoA → Acetyl-CoA + NADH + CO2

Pyruvate oxidation is the step that connects glycolysis and the Krebs cycle. [4] In glycolysis, a single glucose molecule (6 carbons) is split into 2 pyruvates (3 carbons each). Because of this, the link reaction occurs twice for each glucose molecule to produce a total of 2 acetyl-CoA molecules, which can then enter the Krebs cycle.

Energy-generating ions and molecules, such as amino acids and carbohydrates, enter the Krebs cycle as acetyl coenzyme A and oxidize in the cycle. [5] The pyruvate dehydrogenase complex (PDC) catalyzes the decarboxylation of pyruvate, resulting in the synthesis of acetyl-CoA, CO2, and NADH. In eukaryotes, this enzyme complex regulates pyruvate metabolism, and ensures homeostasis of glucose during absorptive and post-absorptive state metabolism. [6] As the Krebs cycle occurs in the mitochondrial matrix, the pyruvate generated during glycolysis in the cytosol is transported across the inner mitochondrial membrane by a pyruvate carrier under aerobic conditions.[ citation needed ]

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<span class="mw-page-title-main">Citric acid cycle</span> Interconnected biochemical reactions releasing energy

The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of biochemical reactions to release the energy stored in nutrients through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The chemical energy released is available under the form of ATP. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism. Even though it is branded as a "cycle", it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.

<span class="mw-page-title-main">Glycolysis</span> Series of interconnected biochemical reactions

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<span class="mw-page-title-main">Pyruvate dehydrogenase complex</span> Three-enzyme complex

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<span class="mw-page-title-main">Mitochondrial matrix</span> Space within the inner membrane of the mitochondrion

In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.

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In biochemistry and metabolism, beta oxidation (also β-oxidation) is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA. Acetyl-CoA enters the citric acid cycle, generating NADH and FADH2, which are electron carriers used in the electron transport chain. It is named as such because the beta carbon of the fatty acid chain undergoes oxidation and is converted to a carbonyl group to start the cycle all over again. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes.

<span class="mw-page-title-main">Mixed acid fermentation</span> Biochemical conversion of six-carbon sugars into acids in bacteria

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In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway. The glycolytic pathway also provides the glycerol with which three fatty acids can combine to form triglycerides, the final product of the lipogenic process. When only two fatty acids combine with glycerol and the third alcohol group is phosphorylated with a group such as phosphatidylcholine, a phospholipid is formed. Phospholipids form the bulk of the lipid bilayers that make up cell membranes and surrounds the organelles within the cells. In addition to cytosolic fatty acid synthesis, there is also mitochondrial fatty acid synthesis (mtFASII), in which malonyl-CoA is formed from malonic acid with the help of malonyl-CoA synthetase (ACSF3), which then becomes the final product octanoyl-ACP (C8) via further intermediate steps.

<span class="mw-page-title-main">Malate dehydrogenase (decarboxylating)</span> Enzyme

Malate dehydrogenase (decarboxylating) (EC 1.1.1.39) or NAD-malic enzyme (NAD-ME) is an enzyme that catalyzes the chemical reaction

Pseudohypoxia refers to a condition that mimics hypoxia, by having sufficient oxygen yet impaired mitochondrial respiration due to a deficiency of necessary co-enzymes, such as NAD+ and TPP. The increased cytosolic ratio of free NADH/NAD+ in cells (more NADH than NAD+) can be caused by diabetic hyperglycemia and by excessive alcohol consumption. Low levels of TPP results from thiamine deficiency.

<span class="mw-page-title-main">Citrate–malate shuttle</span> Series of chemical reactions

The citrate-malate shuttle is a series of chemical reactions, commonly referred to as a biochemical cycle or system, that transports acetyl-CoA in the mitochondrial matrix across the inner and outer mitochondrial membranes for fatty acid synthesis. Mitochondria are enclosed in a double membrane. As the inner mitochondrial membrane is impermeable to acetyl-CoA, the shuttle system is essential to fatty acid synthesis in the cytosol. It plays an important role in the generation of lipids in the liver.

References

  1. "Oxidative decarboxylation of Pyruvate". Bioscience Notes. 2018-07-29. Retrieved 2021-07-09.
  2. "Pyruvate oxidation". Khanacademy.org. Retrieved 25 January 2018.
  3. "Pyruvate Oxidation". Oregonstate.edu. Retrieved 25 January 2018.
  4. Trifiletti, R. R. (2014-01-01), "Thiamine (Vitamin B1) and Beri-Beri", in Aminoff, Michael J.; Daroff, Robert B. (eds.), Encyclopedia of the Neurological Sciences (Second Edition), Oxford: Academic Press, pp. 445–447, doi:10.1016/b978-0-12-385157-4.00116-0, ISBN   978-0-12-385158-1 , retrieved 2020-11-16
  5. Stryer, Lubert; Tymoczko, John L.; Berg, Jeremy M. (2002). "The Citric Acid Cycle". Biochemistry. 5th Edition.
  6. Jordan, Frank; Furey, William; Nemeria, Natalia S.; Patel, Mulchand S. (2014-06-13). "The Pyruvate Dehydrogenase Complexes: Structure-based Function and Regulation". Journal of Biological Chemistry. 289 (24): 16615–16623. doi: 10.1074/jbc.R114.563148 . ISSN   1083-351X. PMC   4059105 . PMID   24798336.