InChI=1S/C35H62N7O17P3S/c1- 4-5-6-7-8-9-10-11-12-13-14-15-26(44)63-19-18-37-25(43)16-17-38-33(47)30(46)35(2,3)21-56-62(53,54)59-61(51,52)55-20-24-29(58-60(48,49)50)28(45)34(57-24)42-23-41-27-31(36)39-22-40-32(27)42/h22-24,28-30,34,45-46H,4-21H2,1-3H3,(H,37,43)(H,38,47)(H,51,52)(H,53,54)(H2,36,39,40)(H2,48,49,50)/t24-,28-,29-,30+,34-/m1/s1 |
| DUAFKXOFBZQTQE-QSGBVPJFSA-N |
| CCCCCCCCCCCCCC(=O)SCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP(O)(O)=O)n1cnc2c(N)ncnc12 |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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acyl donor
Any donor that can transfer acyl groups between molecular entities.
(via acyl-CoA )
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Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
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View more via ChEBI Ontology
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3'-phosphoadenosine 5'-(3-{(3R)-3-hydroxy-2,2-dimethyl-4-oxo-4-[(3-oxo-3-{[2-(tetradecanoylsulfanyl)ethyl]amino}propyl)amino]butyl} dihydrogen diphosphate)
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Myristoyl-CoA
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KEGG COMPOUND
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n-C14:0-CoA
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ChEBI
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n-C14:0-coenzyme A
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ChEBI
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S-tetradecanoyl-coenzyme A
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ChEBI
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Tetradecanoyl-CoA
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KEGG COMPOUND
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3130-72-1
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CAS Registry Number
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ChemIDplus
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8033632
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Reaxys Registry Number
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Reaxys
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Rioux V, Pédrono F, Legrand P (2011)
Regulation of mammalian desaturases by myristic acid: N-terminal myristoylation and other modulations.
Biochimica et biophysica acta 1811, 1-8 [PubMed:20920594]
[show Abstract]
Myristic acid, the 14-carbon saturated fatty acid (C14:0), usually accounts for small amounts (0.5%-1% weight of total fatty acids) in animal tissues. Since it is a relatively rare molecule in the cells, the specific properties and functional roles of myristic acid have not been fully studied and described. Like other dietary saturated fatty acids (palmitic acid, lauric acid), this fatty acid is usually associated with negative consequences for human health. Indeed, in industrialized countries, its excessive consumption correlates with an increase in plasma cholesterol and mortality due to cardiovascular diseases. Nevertheless, one feature of myristoyl-CoA is its ability to be covalently linked to the N-terminal glycine residue of eukaryotic and viral proteins. This reaction is called N-terminal myristoylation. Through the myristoylation of hundreds of substrate proteins, myristic acid can activate many physiological pathways. This review deals with these potentially activated pathways. It focuses on the following emerging findings on the biological ability of myristic acid to regulate the activity of mammalian desaturases: (i) recent findings have described it as a regulator of the Δ4-desaturation of dihydroceramide to ceramide; (ii) studies have demonstrated that it is an activator of the Δ6-desaturation of polyunsaturated fatty acids; and (iii) myristic acid itself is a substrate of some fatty acid desaturases. This article discusses several topics, such as the myristoylation of the dihydroceramide Δ4-desaturase, the myristoylation of the NADH-cytochrome b5 reductase which is part of the whole desaturase complex, and other putative mechanisms. | Frias JA, Richman JE, Erickson JS, Wackett LP (2011)
Purification and characterization of OleA from Xanthomonas campestris and demonstration of a non-decarboxylative Claisen condensation reaction.
The Journal of biological chemistry 286, 10930-10938 [PubMed:21266575]
[show Abstract]
OleA catalyzes the condensation of fatty acyl groups in the first step of bacterial long-chain olefin biosynthesis, but the mechanism of the condensation reaction is controversial. In this study, OleA from Xanthomonas campestris was expressed in Escherichia coli and purified to homogeneity. The purified protein was shown to be active with fatty acyl-CoA substrates that ranged from C(8) to C(16) in length. With limiting myristoyl-CoA (C(14)), 1 mol of the free coenzyme A was released/mol of myristoyl-CoA consumed. Using [(14)C]myristoyl-CoA, the other products were identified as myristic acid, 2-myristoylmyristic acid, and 14-heptacosanone. 2-Myristoylmyristic acid was indicated to be the physiologically relevant product of OleA in several ways. First, 2-myristoylmyristic acid was the major condensed product in short incubations, but over time, it decreased with the concomitant increase of 14-heptacosanone. Second, synthetic 2-myristoylmyristic acid showed similar decarboxylation kinetics in the absence of OleA. Third, 2-myristoylmyristic acid was shown to be reactive with purified OleC and OleD to generate the olefin 14-heptacosene, a product seen in previous in vivo studies. The decarboxylation product, 14-heptacosanone, did not react with OleC and OleD to produce any demonstrable product. Substantial hydrolysis of fatty acyl-CoA substrates to the corresponding fatty acids was observed, but it is currently unclear if this occurs in vivo. In total, these data are consistent with OleA catalyzing a non-decarboxylative Claisen condensation reaction in the first step of the olefin biosynthetic pathway previously found to be present in at least 70 different bacterial strains. | Monzani PS, Pereira HM, Melo FA, Meirelles FV, Oliva G, Cascardo JC (2010)
A new topology of ACBP from Moniliophthora perniciosa.
Biochimica et biophysica acta 1804, 115-123 [PubMed:19782157]
[show Abstract]
Acyl-CoA binding protein (ACBP) is a housekeeping protein and is an essential protein in human cell lines and in Trypanosoma brucei. The ACBP of Moniliophthora perniciosa is composed of 104 amino acids and is possibly a non-classic isoform exclusively from Basidiomycetes. The M. perniciosa acbp gene was cloned, and the protein was expressed and purified. Acyl-CoA ester binding was analyzed by isoelectric focusing, native gel electrophoresis and isothermal titration calorimetry. Our results suggest an increasing affinity of ACBP for longer acyl-CoA esters, such as myristoyl-CoA to arachidoyl-CoA, and best fit modeling indicates two binding sites. ACBP undergoes a shift from a monomeric to a dimeric state, as shown by dynamic light scattering, fluorescence anisotropy and native gel electrophoresis in the absence and presence of the ligand. The protein's structure was determined at 1.6 A resolution and revealed a new topology for ACBP, containing five alpha-helices instead of four. alpha-helices 1, 2, 3 and 4 adopted a bundled arrangement that is unique from the previously determined four-helix folds of ACBP, while alpha-helices 1, 2, 4 and 5 formed a classical four-helix bundle. A MES molecule was found in the CoA binding site, suggesting that the CoA site could be a target for small compound screening. | Beauchamp E, Goenaga D, Le Bloc'h J, Catheline D, Legrand P, Rioux V (2007)
Myristic acid increases the activity of dihydroceramide Delta4-desaturase 1 through its N-terminal myristoylation.
Biochimie 89, 1553-1561 [PubMed:17716801]
[show Abstract]
Dihydroceramide Delta4-desaturase (DES) catalyzes the desaturation of dihydroceramide into ceramide. In mammals, two gene isoforms named DES1 and DES2 have recently been identified. The regulation of these enzymes is still poorly understood. This study was designed to examine the possible N-myristoylation of DES1 and DES2 and the effect of this co-translational modification on dihydroceramide Delta4-desaturase activity. N-MyristoylTransferases (NMT) catalyze indeed the formation of a covalent linkage between myristoyl-CoA and the N-terminal glycine of candidate proteins, as found in the sequence of DES proteins. The expression of both rat DES in COS-7 cells evidenced first that DES1 but not DES2 was associated with an increased dihydroceramide Delta4-desaturase activity. Then, we showed that recombinant DES1 was myristoylated in vivo when expressed in COS-7 cells. In addition, in vitro myristoylation assay with a peptide substrate corresponding to the N-terminal sequence of the protein confirmed that NMT1 has a high affinity for DES1 myristoylation motif (apparent K(m)=3.92 microM). Compared to an unmyristoylable mutant form of DES1 (Gly replaced by an Ala), the dihydroceramide Delta4-desaturase activity of the myristoylable DES1-Gly was reproducibly and significantly higher. Finally, the activity of wild-type DES1 was also linearly increased in the presence of increased concentrations of myristic acid incubated with the cells. These results demonstrate that DES1 is a newly discovered myristoylated protein. This N-terminal modification has a great impact on dihydroceramide Delta4-desaturase activity. These results suggest therefore that myristic acid may play an important role in the biosynthesis of ceramide and in sphingolipid metabolism. | Awad AC, Shin HS, Romsos DR, Gray JI (2004)
Desaturation of myristoyl-CoA to myristoleoyl-CoA by hen liver microsomal delta(9)-desaturase.
Journal of agricultural and food chemistry 52, 4234-4239 [PubMed:15212474]
[show Abstract]
The desaturation of myristoyl-CoA to myristoleoyl-CoA was measured in microsomal preparations of hen liver. The desaturation was maximal at pH 7.4. The enzymatic activity was linear with time up to 10 min and proportional to microsomal protein concentrations. The initial velocity was linear with substrate concentrations between 13 and up to 200 microM. A decrease in desaturation activity was observed at substrate concentrations greater than 266 microM. There was an absolute requirement for reduced pyridine nucleotide (NADH), while a maximum activity was observed at a myristoyl-CoA:NADH mole ratio of 1. Competitive inhibition studies of myristoyl-CoA desaturation suggest that the inhibitors, stearyl and oleyl-CoA, were more effective than palmitoyl-CoA. Free CoA did not inhibit the delta(9)-desaturase system. The desaturation of myristoyl-CoA was stimulated by bovine serum albumin and reduced by cytoplasmic proteins. The effect of cytoplasmic proteins on the enzymatic reaction was completely abolished by trypsin digestion and boiling for 30 min. On the basis of these data, it was concluded that 9,10-desaturation of acyl-CoA derivatives containing 14-18 carbon fatty acyl chains is catalyzed by the same enzyme. | Kishore NS, Wood DC, Mehta PP, Wade AC, Lu T, Gokel GW, Gordon JI (1993)
Comparison of the acyl chain specificities of human myristoyl-CoA synthetase and human myristoyl-CoA:protein N-myristoyltransferase.
The Journal of biological chemistry 268, 4889-4902 [PubMed:8444867]
[show Abstract]
Human myristoyl-CoA synthetase and myristoyl-CoA:protein N-myristoyltransferase (hNmt) have been partially purified from an erythroleukemia cell line. Their substrate specificities were examined using two in vitro assays of enzyme activity together with a panel of C7-C17 saturated fatty acids plus 72 myristic acid analogs containing oxygen, sulfur, ketocarbonyl, ester, amide, cis and trans double bonds, triple bonds, and para-substituted phenyl groups. There is an inverse relationship between the polarity and the activity of C14 fatty acid substrates of myristoyl-CoA synthetase. Surveys of tetradecenoic and tetradecynoic acids suggest that myristate is bound to the synthetase in a bent conformation with a principal bend occurring in the vicinity of C5-C6. The synthetase can tolerate a somewhat wider range of physical chemical properties in acyl chains than can the monomeric hNmt. However, like myristoyl-CoA synthetase, there is an inverse relationship between acyl chain polarity and the activities of hNmt's acyl-CoA substrates. Moreover, the acyl chain of myristoyl-CoA appears to be bound to hNmt in a bent conformation with bends located in the vicinity of C5 and C8. The acyl chain specificities of both enzymes make them well suited to utilize efficiently any cellular pools of 5Z-tetradecenoic and 5Z,8Z-tetradecadienoic acids and their CoA derivatives. This feature may account for the recent observation that in some mammalian cell lineages, certain N-myristoyl-proteins are heterogeneously acylated with these C14 fatty acids. Finally, the acyl-CoA binding sites of human and Saccharomyces cerevisiae Nmts appear to have been highly conserved. Given their overlapping yet distinct peptide substrate specificities, development of species-specific inhibitors of Nmts should probably focus on structural features recognized in the enzymes' peptide substrates rather than in the acyl chain of their acyl-CoA substrates. |
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