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 B 5 ), and adenosine triphosphate (ATP).
31-644: CATC may refer to: Carnitine O-acetyltransferase , an enzyme Catapult C , a electronic design automation product CATC Design School , in Australia Central Arkansas Telephone Cooperative Civil Aviation Technology College , Iran Civil Aviation Training Center , Iran College of Air Traffic Control , in the United Kingdom Combined Arms Training Centre , of
62-399: A thiol , it can react with carboxylic acids to form thioesters , thus functioning as an acyl group carrier. It assists in transferring fatty acids from the cytoplasm to mitochondria . A molecule of coenzyme A carrying an acyl group is also referred to as acyl-CoA . When it is not attached to an acyl group, it is usually referred to as 'CoASH' or 'HSCoA'. This process facilitates
93-475: A C domain, and is composed of 20 α helices and 16 β strands. The N domain consists of an eight-stranded β sheet flanked on both sides by eight α helices. A six-stranded mixed β sheet and eleven α helices comprise the enzyme’s C domain. When compared, the cores of the two domains reflect significantly similar peptide backbone folding. This occurs despite the fact that only 4% of the amino acids that comprise those peptide backbones corresponds to one another. His343
124-628: A bifunctional enzyme called COASY . This pathway is regulated by product inhibition. CoA is a competitive inhibitor for Pantothenate Kinase, which normally binds ATP. Coenzyme A, three ADP, one monophosphate, and one diphosphate are harvested from biosynthesis. Coenzyme A can be synthesized through alternate routes when intracellular coenzyme A level are reduced and the de novo pathway is impaired. In these pathways, coenzyme A needs to be provided from an external source, such as food, in order to produce 4′-phosphopantetheine . Ectonucleotide pyrophosphates (ENPP) degrade coenzyme A to 4′-phosphopantetheine,
155-402: A primordial prebiotic world. Coenzyme A is produced commercially via extraction from yeast, however this is an inefficient process (yields approximately 25 mg/kg) resulting in an expensive product. Various ways of producing CoA synthetically, or semi-synthetically have been investigated although none are currently operating at an industrial scale. Since coenzyme A is, in chemical terms,
186-447: A stable molecule in organisms. Acyl carrier proteins (ACP) (such as ACP synthase and ACP degradation) are also used to produce 4′-phosphopantetheine. This pathway allows for 4′-phosphopantetheine to be replenished in the cell and allows for the conversion to coenzyme A through enzymes, PPAT and PPCK. A 2024 article detailed a plausible chemical synthesis mechanism for the pantetheine component (the main functional part) of coenzyme A in
217-506: Is an enzyme that encoded by the CRAT gene that catalyzes the chemical reaction where the acetyl group displaces the hydrogen atom in the central hydroxyl group of carnitine. Thus, the two substrates of this enzyme are acetyl-CoA and carnitine , whereas its two products are CoA and O- acetylcarnitine . The reaction is highly reversible and does not depend on the order in which substrates bind. Different subcellular localizations of
248-438: Is composed of the C domain β sheet and particular residues from the N domain. Upon binding, a face of carnitine is left exposed to the space outside the enzyme. Like CoA, carnitine forms a hydrogen bond with the ε2 nitrogen on His343. In the case of carnitine, the bond is formed with its 3-hydroxyl group. This CRAT catalysis is stereospecific for carnitine, as the stereoisomer of the 3-hydroxyl group cannot sufficiently interact with
279-474: Is different from Wikidata All article disambiguation pages All disambiguation pages Carnitine O-acetyltransferase 1NM8 , 1S5O 1384 12908 ENSG00000095321 ENSMUSG00000026853 P43155 P47934 NM_001346547 NM_001346548 NM_001346549 NM_007760 NP_001333478 NP_003994 NP_031786 Carnitine O-acetyltransferase also called carnitine acetyltransferase ( CRAT , or CAT ) ( EC 2.3.1.7 )
310-406: Is implemented by regulation of acetyl-CoA carboxylase , which catalyzes the committed step in fatty acid synthesis. Insulin stimulates acetyl-CoA carboxylase, while epinephrine and glucagon inhibit its activity. During cell starvation, coenzyme A is synthesized and transports fatty acids in the cytosol to the mitochondria. Here, acetyl-CoA is generated for oxidation and energy production. In
341-445: Is known to interact with NEDD8 , PEX5 , SUMO1 . Coenzyme A 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. Coenzyme A
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#1732851718732372-429: Is now free to attack the acetyl group of acetyl-CoA or acetylcarnitine at its carbonyl site. The reaction proceeds directly, without the formation of a His343-acetyl intermediate. It is possible for catalysis to occur with only one of the two substrates. If either acetyl-CoA or acetylcarnitine binds to CRAT, a water molecule may fill the other binding site and act as an acetyl group acceptor. The literature suggests that
403-597: Is termed protein CoAlation (Protein-S-SCoA), which plays a similar role to protein S -glutathionylation by preventing the irreversible oxidation of the thiol group of cysteine residues. Using anti-coenzyme A antibody and liquid chromatography tandem mass spectrometry ( LC-MS/MS ) methodologies, more than 2,000 CoAlated proteins were identified from stressed mammalian and bacterial cells. The majority of these proteins are involved in cellular metabolism and stress response. Different research studies have focused on deciphering
434-819: Is termed protein deCoAlation. So far, two bacterial proteins, Thioredoxin A and Thioredoxin-like protein (YtpP), are shown to deCoAlate proteins. Coenzyme A is available from various chemical suppliers as the free acid and lithium or sodium salts. The free acid of coenzyme A is detectably unstable, with around 5% degradation observed after 6 months when stored at −20 °C, and near complete degradation after 1 month at 37 °C. The lithium and sodium salts of CoA are more stable, with negligible degradation noted over several months at various temperatures. Aqueous solutions of coenzyme A are unstable above pH 8, with 31% of activity lost after 24 hours at 25 °C and pH 8. CoA stock solutions are relatively stable when frozen at pH 2–6. The major route of CoA activity loss
465-437: Is the catalytic residue in CRAT. It is located at the interface between the enzyme’s C and N domains towards the heart of CRAT. His343 is accessible via two 15-18 Å channels that approach the residue from opposite ends of the CRAT enzyme. These channels are utilized by the substrates of CRAT, one channel for carnitine, and one for CoA. The side chain of His343 is positioned irregularly, with the δ ring nitrogen hydrogen bonded to
496-420: Is the primary input in the citric acid cycle and is obtained from glycolysis , amino acid metabolism, and fatty acid beta oxidation. This process is the body's primary catabolic pathway and is essential in breaking down the building blocks of the cell such as carbohydrates , amino acids , and lipids . When there is excess glucose, coenzyme A is used in the cytosol for synthesis of fatty acids. This process
527-473: Is therefore not considered essential. These bacteria synthesize pantothenate from the amino acid aspartate and a metabolite in valine biosynthesis. In all living organisms, coenzyme A is synthesized in a five-step process that requires four molecules of ATP, pantothenate and cysteine (see figure): Enzyme nomenclature abbreviations in parentheses represent mammalian, other eukaryotic, and prokaryotic enzymes respectively. In mammals steps 4 and 5 are catalyzed by
558-681: The Australian Army Confédération africaine des travailleurs croyants (disambiguation) , various trade unions in Africa Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title CATC . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=CATC&oldid=1234811873 " Category : Disambiguation pages Hidden categories: Short description
589-589: The CRAT carnitine binding site. CRAT undergoes minor conformational changes upon binding with carnitine. The His343 residue at the active site of CRAT acts as a base that is able to deprotonate the CoA thiol group or the Carnitine 3’-hydroxyl group depending on the direction of the reaction. The structure of CRAT optimizes this reaction by causing direct hydrogen bonding between the His343 and both substrates. The deprotonated group
620-461: The CRAT mRNAs are thought to result from alternative splicing of the CRAT gene suggested by the divergent sequences in the 5' region of peroxisomal and mitochondrial CRAT cDNAs and the location of an intron where the sequences diverge. The alternatively splicing of this gene results in three distinct isoforms, one of which contains an N-terminal mitochondrial transit peptide, and has been shown to be located in mitochondria. This enzyme belongs to
651-619: The Nobel Prize in Physiology or Medicine "for his discovery of co-enzyme A and its importance for intermediary metabolism". Coenzyme A is naturally synthesized from pantothenate (vitamin B 5 ), which is found in food such as meat, vegetables, cereal grains, legumes, eggs, and milk. In humans and most living organisms, pantothenate is an essential vitamin that has a variety of functions. In some plants and bacteria, including Escherichia coli , pantothenate can be synthesised de novo and
SECTION 20
#1732851718732682-412: The carbonyl oxygen on the amino acid backbone. Due to the fact that CRAT binds CoA, rather than acetyl-CoA, it appears that CRAT possesses the ability to hydrolyze acetyl-CoA, before interacting with the lone CoA fragment at the binding site. CoA is bound in a linear conformation with its pantothenic arm binding at the active site. Here, the pantothenic arm’s terminal thiol group and the ε nitrogen on
713-456: The catalytic His343 side chain form a hydrogen bond. The 3’-phosphate on CoA forms interactions with residues Lys419 and Lys423. Also at the binding site, the residues Asp430 and Glu453 form a direct hydrogen bond to one another. If either residue exhibits a mutation, can result in a decrease in CRAT activity. Carnitine binds to CRAT in a partially folded state, with its hydroxyl group and carboxyl group facing opposite directions. The site itself
744-444: The citric acid cycle, coenzyme A works as an allosteric regulator in the stimulation of the enzyme pyruvate dehydrogenase . Discovery of the novel antioxidant function of coenzyme A highlights its protective role during cellular stress. Mammalian and Bacterial cells subjected to oxidative and metabolic stress show significant increase in the covalent modification of protein cysteine residues by coenzyme A. This reversible modification
775-400: The coenzyme A-mediated regulation of proteins. Upon protein CoAlation, inhibition of the catalytic activity of different proteins (e.g. metastasis suppressor NME1 , peroxiredoxin 5 , GAPDH , among others) is reported. To restore the protein's activity, antioxidant enzymes that reduce the disulfide bond between coenzyme A and the protein cysteine residue play an important role. This process
806-679: The family of transferases , to be specific those acyltransferases transferring groups other than aminoacyl groups. The systematic name of this enzyme class is acetyl-CoA:carnitine O-acetyltransferase. Other names in common use include acetyl-CoA-carnitine O-acetyltransferase, acetylcarnitine transferase, carnitine acetyl coenzyme A transferase, carnitine acetylase, carnitine acetyltransferase, carnitine-acetyl-CoA transferase, and CATC. This enzyme participates in alanine and aspartate metabolism . In general, carnitine acetyltransferases have molecular weights of about 70 kDa, and contain approximately 600 residues1. CRAT contains two domains, an N domain and
837-426: The production of fatty acids in cells, which are essential in cell membrane structure. Coenzyme A is also the source of the phosphopantetheine group that is added as a prosthetic group to proteins such as acyl carrier protein and formyltetrahydrofolate dehydrogenase . Coenzyme A is one of five crucial coenzymes that are necessary in the reaction mechanism of the citric acid cycle . Its acetyl-coenzyme A form
868-461: The trimethylammonium group on carnitine may be a crucial factor in CRAT catalysis. This group exhibits a positive charge that stabilizes the oxyanion in the reaction’s intermediate. This idea is supported by the fact the positive charge of carnitine is unnecessary for active site binding, but vital for the catalysis to proceed. This has been proven to be the case through the synthesis of a carnitine analog lacking its trimethylammonium group. This compound
899-756: Was able to compete with carnitine in binding to CRAT, but was unable to induce a reaction. The emergence of substrate-assisted catalysis has opened up new strategies for increasing synthetic substrate specificity. There is evidence that suggests that CRAT activity is necessary for the cell cycle to proceed from the G1 phase to the S phase. Those with an inherited deficiency in CRAT activity are at risk for developing severe heart and neurological problems. Reduced CRAT activity can be found in individuals suffering from Alzheimer’s disease. CRAT and its family of enzymes have great potential as targets for developing therapeutic treatments for Type 2 diabetes and other diseases. CRAT
930-435: Was evident in all organs of the animals. He was able to isolate and purify the factor from pig liver and discovered that its function was related to a coenzyme that was active in choline acetylation. Work with Beverly Guirard , Nathan Kaplan , and others determined that pantothenic acid was a central component of coenzyme A. The coenzyme was named coenzyme A to stand for "activation of acetate". In 1953, Fritz Lipmann won
961-488: Was identified by Fritz Lipmann in 1946, who also later gave it its name. Its structure was determined during the early 1950s at the Lister Institute , London, together by Lipmann and other workers at Harvard Medical School and Massachusetts General Hospital . Lipmann initially intended to study acetyl transfer in animals, and from these experiments he noticed a unique factor that was not present in enzyme extracts but