Acetyl-CoA in the context of "Coenzyme A"

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👉 Acetyl-CoA in the context of Coenzyme A

Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenate (vitamin B5), and adenosine triphosphate (ATP).

In its acetyl form, coenzyme A is a highly versatile molecule, serving metabolic functions in both the anabolic and catabolic pathways. Acetyl-CoA is utilised in the post-translational regulation and allosteric regulation of pyruvate dehydrogenase and carboxylase to maintain and support the partition of pyruvate synthesis and degradation.

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Acetyl-CoA in the context of Pyruvic acid

Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO, is an intermediate in several metabolic pathways throughout the cell.

Pyruvic acid can be made from glucose through glycolysis, converted back to carbohydrates (such as glucose) via gluconeogenesis, or converted to fatty acids through a reaction with acetyl-CoA. It can also be used to construct the amino acid alanine and can be converted into ethanol or lactic acid via fermentation.

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Acetyl-CoA in the context of Fatty acid degradation

Fatty acid degradation is the process in which fatty acids are broken down into their metabolites, in the end generating acetyl-CoA, the entry molecule for the citric acid cycle, the main energy supply of living organisms, including bacteria and animals. It includes three major steps:

  • Lipolysis of and release from adipose tissue
  • Activation and transport into mitochondria
  • β-oxidation
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Acetyl-CoA in the context of Fatty acid synthesis

In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes. Two de novo fatty acid syntheses can be distinguished: cytosolic fatty acid synthesis (FAS/FASI) and mitochondrial fatty acid synthesis (mtFAS/mtFASII). 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 (by means of ester bonds) to form triglycerides (also known as "triacylglycerols" – to distinguish them from fatty "acids" – or simply as "fat"), 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 (such as the cell nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, etc.).

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Acetyl-CoA in the context of Citric acid cycle

The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle, or TCA cycle (tricarboxylic acid cycle)—is a series of biochemical reactions that release the energy stored in nutrients through acetyl-CoA oxidation. The energy released is available in the form of ATP. The Krebs cycle is used by organisms that generate energy via respiration, either anaerobically or aerobically (organisms that ferment use different pathways). In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, which are used in other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest metabolism components. Even though it is branded as a "cycle", it is not necessary for metabolites to follow a specific route; at least three alternative pathways of the citric acid cycle are recognized.

Its name is derived from the citric acid (a tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH) that is consumed and then regenerated by this sequence of reactions. The cycle consumes acetate (in the form of acetyl-CoA) and water and reduces NAD to NADH, releasing carbon dioxide. The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable chemical energy in the form of ATP.

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Acetyl-CoA in the context of Lipogenesis

In biochemistry, lipogenesis is the conversion of fatty acids and glycerol into fats, or a metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. Lipogenesis encompasses both fatty acid and triglyceride synthesis, with the latter being the process by which fatty acids are esterified to glycerol before being packaged into very-low-density lipoprotein (VLDL). Fatty acids are produced in the cytoplasm of cells by repeatedly adding two-carbon units to acetyl-CoA. Triacylglycerol synthesis, on the other hand, occurs in the endoplasmic reticulum membrane of cells by bonding three fatty acid molecules to a glycerol molecule. Both processes take place mainly in liver and adipose tissue. Nevertheless, it also occurs to some extent in other tissues such as the gut and kidney. After being packaged into VLDL in the liver, the resulting lipoprotein is then secreted directly into the blood for delivery to peripheral tissues.

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Acetyl-CoA in the context of Histone acetyltransferases

Histone acetyltransferases (HATs) are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl-CoA to form ε-N-acetyllysine. DNA is wrapped around histones, and, by transferring an acetyl group to the histones, genes can be turned on and off. In general, histone acetylation increases gene expression.

In general, histone acetylation is linked to transcriptional activation and associated with euchromatin. Euchromatin, which is less densely compact, allows transcription factors to bind more easily to regulatory sites on DNA, causing transcriptional activation. When it was first discovered, it was thought that acetylation of lysine neutralizes the positive charge normally present, thus reducing affinity between histone and (negatively charged) DNA, which renders DNA more accessible to transcription factors. Research has emerged, since, to show that lysine acetylation and other posttranslational modifications of histones generate binding sites for specific protein–protein interaction domains, such as the acetyllysine-binding bromodomain. Histone acetyltransferases can also acetylate non-histone proteins, such as nuclear receptors and other transcription factors to facilitate gene expression.

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