Acetyl-coenzyme A
Acetyl-coenzyme A (acetyl-CoA) is so central for intermediate metabolism that hypothetical reconstructions of the origin of life postulate its involvement in ancestral methanotrophic reactions performed by the last common precursor of prokaryotes. From archaebacteria to mammalians, acetyl-CoA occupies a critical position in multiple cellular processes, as a metabolic intermediate, as a precursor of anabolic reactions, as an allosteric regulator of enzymatic activities, and as a key determinant of protein acetylation. Acetyl-CoA is indeed the actual molecule through which glycolytic pyruvate enters the tricarboxylic acid (TCA) cycle, is a key precursor of lipid synthesis, and is the sole donor of the acetyl groups for acetylation.
The structure of the important activated carrier molecule acetyl CoA.
A ball-and-stick model is shown above the structure. The sulfur atom (yellow) forms a thioester bond to acetate. Because this is a high-energy linkage, releasing a large amount of free energy when it is hydrolyzed, the acetate
molecule can be readily transferred to other molecules. 2
Acetyl-CoA is a membrane-impermeant molecule constituted by an acetyl moiety (CH3CO) linked to coenzyme A (CoA), a derivative of vitamin B5 and cysteine, through a thioester bond (Shi and Tu, 2015). As thioester bonds are energy rich, the chemical structure of acetyl-CoA facilitates the transfer of the acetyl moiety to a variety of acceptor molecules, including amino groups on proteins (Shi and Tu, 2015). Acetylation can occur as a co-translational event. In this setting, Nα acetyltransferases (NATs) transfer an acetyl group from acetyl-CoA to the α-amino group of the N-terminal residue of the protein (which generally is serine, alanine, glycine, threonine, valine, or cysteine), once the initiator methionine has been removed by methionine aminopeptidases. N-terminal acetylation affects the vast majority of human proteins, determining their stability, localization, and function (Hollebeke et al., 2012).
Biosynthesis of acetyl coenzyme A
One example of the use of ATP to activate a carboxylic acid derivative is in the biosynthesis of acetyl-coenzyme A. This is carried out in bacteria by the action of two enzymes: acetate kinase, which activates acetate as acetyl phosphate using ATP as a cofactor; and phosphotransacetylase, which transfers the acetyl group onto coenzyme A (see Figure below). Phosphorylation of serine and tyrosine residues on the surface of proteins is a very important
reaction in cell signalling pathways. These reactions are catalysed by the serine/threonine and tyrosine protein kinases, which also use ATP as coenzyme.
The bacterial enzymes acetate kinase (AK) and phosphotransacetylase (PTA) form a key pathway for synthesis of the central metabolic intermediate acetyl coenzyme A (acetyl-CoA) from acetate or for generation of ATP from excess acetyl-CoA. 4 In molecular biology, acetate kinase, which is predominantly found in micro-organisms, facilitates the production of acetyl-CoA by phosphorylating acetate in the presence of ATP and a divalent cation. 3
One example of the use of ATP to activate a carboxylic acid derivative is in the biosynthesis of acetyl coenzyme A. This is carried out in bacteria by the action of two enzymes: acetate kinase, which activates acetate as acetyl phosphate using ATP as a cofactor; and phosphotransacetylase, which transfers the acetyl group onto coenzyme A 5
1. https://www.sciencedirect.com/science/article/pii/S1550413115002260
2. Molecular biology of the Cell, 6th Ed. page 69
3. https://en.wikipedia.org/wiki/Acetate_kinase
4. http://www.cell.com.sci-hub.tw/trends/microbiology/fulltext/S0966-842X(06)00093-X
5. Introduction to Enzyme and Coenzyme Chemistry, page 109
Acetyl-coenzyme A (acetyl-CoA) is so central for intermediate metabolism that hypothetical reconstructions of the origin of life postulate its involvement in ancestral methanotrophic reactions performed by the last common precursor of prokaryotes. From archaebacteria to mammalians, acetyl-CoA occupies a critical position in multiple cellular processes, as a metabolic intermediate, as a precursor of anabolic reactions, as an allosteric regulator of enzymatic activities, and as a key determinant of protein acetylation. Acetyl-CoA is indeed the actual molecule through which glycolytic pyruvate enters the tricarboxylic acid (TCA) cycle, is a key precursor of lipid synthesis, and is the sole donor of the acetyl groups for acetylation.
The structure of the important activated carrier molecule acetyl CoA.
A ball-and-stick model is shown above the structure. The sulfur atom (yellow) forms a thioester bond to acetate. Because this is a high-energy linkage, releasing a large amount of free energy when it is hydrolyzed, the acetate
molecule can be readily transferred to other molecules. 2
Acetyl-CoA is a membrane-impermeant molecule constituted by an acetyl moiety (CH3CO) linked to coenzyme A (CoA), a derivative of vitamin B5 and cysteine, through a thioester bond (Shi and Tu, 2015). As thioester bonds are energy rich, the chemical structure of acetyl-CoA facilitates the transfer of the acetyl moiety to a variety of acceptor molecules, including amino groups on proteins (Shi and Tu, 2015). Acetylation can occur as a co-translational event. In this setting, Nα acetyltransferases (NATs) transfer an acetyl group from acetyl-CoA to the α-amino group of the N-terminal residue of the protein (which generally is serine, alanine, glycine, threonine, valine, or cysteine), once the initiator methionine has been removed by methionine aminopeptidases. N-terminal acetylation affects the vast majority of human proteins, determining their stability, localization, and function (Hollebeke et al., 2012).
Biosynthesis of acetyl coenzyme A
One example of the use of ATP to activate a carboxylic acid derivative is in the biosynthesis of acetyl-coenzyme A. This is carried out in bacteria by the action of two enzymes: acetate kinase, which activates acetate as acetyl phosphate using ATP as a cofactor; and phosphotransacetylase, which transfers the acetyl group onto coenzyme A (see Figure below). Phosphorylation of serine and tyrosine residues on the surface of proteins is a very important
reaction in cell signalling pathways. These reactions are catalysed by the serine/threonine and tyrosine protein kinases, which also use ATP as coenzyme.
The bacterial enzymes acetate kinase (AK) and phosphotransacetylase (PTA) form a key pathway for synthesis of the central metabolic intermediate acetyl coenzyme A (acetyl-CoA) from acetate or for generation of ATP from excess acetyl-CoA. 4 In molecular biology, acetate kinase, which is predominantly found in micro-organisms, facilitates the production of acetyl-CoA by phosphorylating acetate in the presence of ATP and a divalent cation. 3
One example of the use of ATP to activate a carboxylic acid derivative is in the biosynthesis of acetyl coenzyme A. This is carried out in bacteria by the action of two enzymes: acetate kinase, which activates acetate as acetyl phosphate using ATP as a cofactor; and phosphotransacetylase, which transfers the acetyl group onto coenzyme A 5
1. https://www.sciencedirect.com/science/article/pii/S1550413115002260
2. Molecular biology of the Cell, 6th Ed. page 69
3. https://en.wikipedia.org/wiki/Acetate_kinase
4. http://www.cell.com.sci-hub.tw/trends/microbiology/fulltext/S0966-842X(06)00093-X
5. Introduction to Enzyme and Coenzyme Chemistry, page 109
