Coenzyme A

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Coenzyme A (CoA, CoASH, or HSCoA) 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, such as acetyl-CoA) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenate, and adenosine triphosphate (ATP).

The structure of coenzyme A was identified in the early 1950s at the Lister Institute, London, together by Fritz 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 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. The coenzyme was named coenzyme A to stand for “activation of acetate.” In 1953, Fritz Lipmann won 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 B5), 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 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 eukaryotic and prokaryotic enzymes respectively. 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.

New research shows that 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, a stable molecule in organisms. Acyl carrier proteins (ACP) (such as ACP synthase and ACP degradation) are also used to produce 4′-phosphopantetheine. This pathways allows for 4′-phosphopantetheine to be replenished in the cell and allows for the conversion to coenzyme A through enzymes, PPAT and PPCK.

This page was last edited on 5 January 2018, at 21:39.
Reference: https://en.wikipedia.org/wiki/Coenzyme_A under CC BY-SA license.

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