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| coenzyme A |
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| CHEBI:15346 |
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| A thiol comprising a panthothenate unit in phosphoric anhydride linkage with a 3',5'-adenosine diphosphate unit; and an aminoethanethiol unit. |
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This entity has been manually annotated by the ChEBI Team.
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CHEBI:741566, CHEBI:41631, CHEBI:41597, CHEBI:3771, CHEBI:13294, CHEBI:13295, CHEBI:13298, CHEBI:23355
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| ZINC000008551087 |
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Molfile
XML
SDF
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more structures >>
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call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js
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| 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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Read full article at Wikipedia
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InChI=1S/C21H36N7O16P3S/c1- 21(2,16(31)19(32)24-4-3-12(29)23-5-6-48)8-41-47(38,39)44-46(36,37)40-7-11-15(43-45(33,34)35)14(30)20(42-11)28-10-27-13-17(22)25-9-26-18(13)28/h9-11,14-16,20,30-31,48H,3-8H2,1-2H3,(H,23,29)(H,24,32)(H,36,37)(H,38,39)(H2,22,25,26)(H2,33,34,35)/t11-,14-,15-,16+,20-/m1/s1 |
| RGJOEKWQDUBAIZ-IBOSZNHHSA-N |
| CC(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)[C@@H](O)C(=O)NCCC(=O)NCCS |
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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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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).
coenzyme
A low-molecular-weight, non-protein organic compound participating in enzymatic reactions as dissociable acceptor or donor of chemical groups or electrons.
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View more via ChEBI Ontology
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Outgoing
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coenzyme A
(CHEBI:15346)
has functional parent
3'-phosphate-adenosine-5'-diphosphate
(CHEBI:44672)
coenzyme A
(CHEBI:15346)
has role
Escherichia coli metabolite
(CHEBI:76971)
coenzyme A
(CHEBI:15346)
has role
coenzyme
(CHEBI:23354)
coenzyme A
(CHEBI:15346)
has role
mouse metabolite
(CHEBI:75771)
coenzyme A
(CHEBI:15346)
is a
6-aminopurines
(CHEBI:20706)
coenzyme A
(CHEBI:15346)
is a
nucleotide derivative
(CHEBI:231540)
coenzyme A
(CHEBI:15346)
is a
secondary carboxamide
(CHEBI:140325)
coenzyme A
(CHEBI:15346)
is a
thiol
(CHEBI:29256)
coenzyme A
(CHEBI:15346)
is conjugate acid of
coenzyme A(4−)
(CHEBI:57287)
|
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Incoming
|
γ-butyrobetainyl-CoA
(CHEBI:61517)
has functional parent
coenzyme A
(CHEBI:15346)
(1-hydroxycyclohexyl)acetyl-CoA
(CHEBI:15448)
has functional parent
coenzyme A
(CHEBI:15346)
(2,3,3-trimethyl-5-oxocyclopent-3-enyl)acetyl-CoA
(CHEBI:27866)
has functional parent
coenzyme A
(CHEBI:15346)
(2-trans,6-cis)-dodeca-2,6-dienoyl-CoA
(CHEBI:28387)
has functional parent
coenzyme A
(CHEBI:15346)
(2E,4Z)-deca-2,4-dienoyl-CoA
(CHEBI:29119)
has functional parent
coenzyme A
(CHEBI:15346)
(3S)-citryl-CoA
(CHEBI:15459)
has functional parent
coenzyme A
(CHEBI:15346)
(3Z,6Z)-dodecadienoyl-CoA
(CHEBI:28002)
has functional parent
coenzyme A
(CHEBI:15346)
(E)-4-(trimethylammonio)but-2-enoyl-CoA
(CHEBI:61123)
has functional parent
coenzyme A
(CHEBI:15346)
(E,E)-piperonyl-CoA
(CHEBI:15464)
has functional parent
coenzyme A
(CHEBI:15346)
(R)-methylmalonyl-CoA
(CHEBI:15465)
has functional parent
coenzyme A
(CHEBI:15346)
(R)-phenyllactoyl-CoA
(CHEBI:11010)
has functional parent
coenzyme A
(CHEBI:15346)
(S)-3-hydroxyhexanoyl-CoA
(CHEBI:28276)
has functional parent
coenzyme A
(CHEBI:15346)
(S)-methylmalonyl-CoA
(CHEBI:15466)
has functional parent
coenzyme A
(CHEBI:15346)
2'-(5''-phosphoribosyl)-3'-dephospho-CoA
(CHEBI:65338)
has functional parent
coenzyme A
(CHEBI:15346)
2'-(5-triphosphoribosyl)-3'-dephospho-CoA
(CHEBI:11392)
has functional parent
coenzyme A
(CHEBI:15346)
2-amino-5-oxocyclohex-1-enecarbonyl-CoA
(CHEBI:18206)
has functional parent
coenzyme A
(CHEBI:15346)
2-benzylsuccinyl-CoA
(CHEBI:22746)
has functional parent
coenzyme A
(CHEBI:15346)
2-furoyl-CoA
(CHEBI:15474)
has functional parent
coenzyme A
(CHEBI:15346)
2-methylbutanoyl-CoA
(CHEBI:15477)
has functional parent
coenzyme A
(CHEBI:15346)
3'-dephospho-CoA
(CHEBI:15468)
has functional parent
coenzyme A
(CHEBI:15346)
3,4,4-trimethylhepta-2,5-dienoyl-CoA
(CHEBI:23608)
has functional parent
coenzyme A
(CHEBI:15346)
3,4-dihydro-7-methoxy-2-methylene-3-oxo-2H-1,4-benzoxazine-5-carbonyl-CoA
(CHEBI:1373)
has functional parent
coenzyme A
(CHEBI:15346)
3-(4-methylpent-3-en-1-yl)pent-2-enedioyl-CoA
(CHEBI:15480)
has functional parent
coenzyme A
(CHEBI:15346)
3-hydroxy-3-(4-methylpent-3-en-1-yl)glutaryl-CoA
(CHEBI:15483)
has functional parent
coenzyme A
(CHEBI:15346)
3-hydroxy-3-methylbutyl-CoA
(CHEBI:27874)
has functional parent
coenzyme A
(CHEBI:15346)
3-isopropenylpimeloyl-CoA
(CHEBI:37439)
has functional parent
coenzyme A
(CHEBI:15346)
3-methylbut-3-enoyl-CoA
(CHEBI:28188)
has functional parent
coenzyme A
(CHEBI:15346)
3-oxooctadecanoyl-CoA
(CHEBI:50571)
has functional parent
coenzyme A
(CHEBI:15346)
4,8,12-trimethyltridecanoyl-CoA
(CHEBI:15495)
has functional parent
coenzyme A
(CHEBI:15346)
5-hydroxythiophene-2-carbonyl-CoA
(CHEBI:15502)
has functional parent
coenzyme A
(CHEBI:15346)
6-hydroxycyclohex-1-ene-1-carbonyl-CoA
(CHEBI:15505)
has functional parent
coenzyme A
(CHEBI:15346)
6-hydroxyhex-3-enoyl-CoA
(CHEBI:49281)
has functional parent
coenzyme A
(CHEBI:15346)
6-oxocyclohex-1-ene-1-carbonyl-CoA
(CHEBI:28168)
has functional parent
coenzyme A
(CHEBI:15346)
cis-dodec-3-enoyl-CoA
(CHEBI:27989)
has functional parent
coenzyme A
(CHEBI:15346)
cis-geranoyl-CoA
(CHEBI:15523)
has functional parent
coenzyme A
(CHEBI:15346)
cis-tetradec-11-enoyl-CoA
(CHEBI:15461)
has functional parent
coenzyme A
(CHEBI:15346)
cis-tetradec-3-enoyl-CoA
(CHEBI:62014)
has functional parent
coenzyme A
(CHEBI:15346)
N-methylanthraniloyl-CoA
(CHEBI:30305)
has functional parent
coenzyme A
(CHEBI:15346)
O3-(phosphoribosyl dephospho-CoA)-L-serine
(CHEBI:21979)
has functional parent
coenzyme A
(CHEBI:15346)
S-alkyl-CoA
(CHEBI:62204)
has functional parent
coenzyme A
(CHEBI:15346)
S-nitroso-coenzyme A
(CHEBI:229721)
has functional parent
coenzyme A
(CHEBI:15346)
trans-3-methylglutaconyl-CoA
(CHEBI:15488)
has functional parent
coenzyme A
(CHEBI:15346)
trans-4-carboxybut-2-enoyl-CoA
(CHEBI:15497)
has functional parent
coenzyme A
(CHEBI:15346)
trans-dec-2-enoyl-CoA
(CHEBI:10723)
has functional parent
coenzyme A
(CHEBI:15346)
trans-dodec-2-enoyl-CoA
(CHEBI:15471)
has functional parent
coenzyme A
(CHEBI:15346)
trans-feruloyl-CoA
(CHEBI:15511)
has functional parent
coenzyme A
(CHEBI:15346)
trans-hex-2-enoyl-CoA
(CHEBI:28706)
has functional parent
coenzyme A
(CHEBI:15346)
trans-oct-2-enoyl-CoA
(CHEBI:27537)
has functional parent
coenzyme A
(CHEBI:15346)
trans-tetradec-11-enoyl-CoA
(CHEBI:15460)
has functional parent
coenzyme A
(CHEBI:15346)
trans-tetradec-2-enoyl-CoA
(CHEBI:27721)
has functional parent
coenzyme A
(CHEBI:15346)
acetyl-CoA
(CHEBI:15351)
has functional parent
coenzyme A
(CHEBI:15346)
acryloyl-CoA
(CHEBI:15513)
has functional parent
coenzyme A
(CHEBI:15346)
acyl-CoA
(CHEBI:17984)
has functional parent
coenzyme A
(CHEBI:15346)
alk-2-enoyl-CoA
(CHEBI:15469)
has functional parent
coenzyme A
(CHEBI:15346)
but-2-enoyl-CoA
(CHEBI:36926)
has functional parent
coenzyme A
(CHEBI:15346)
butyryl-CoA
(CHEBI:15517)
has functional parent
coenzyme A
(CHEBI:15346)
cinnamoyl-CoA
(CHEBI:15463)
has functional parent
coenzyme A
(CHEBI:15346)
citramalyl-CoA
(CHEBI:15457)
has functional parent
coenzyme A
(CHEBI:15346)
CoA-glutathione
(CHEBI:17586)
has functional parent
coenzyme A
(CHEBI:15346)
cyclohexa-1,4-diene-1-carbonyl-CoA
(CHEBI:28443)
has functional parent
coenzyme A
(CHEBI:15346)
cyclohexa-1,5-diene-1-carbonyl-CoA
(CHEBI:15520)
has functional parent
coenzyme A
(CHEBI:15346)
cyclohexa-2,5-diene-1-carbonyl-CoA
(CHEBI:27610)
has functional parent
coenzyme A
(CHEBI:15346)
decanoyl-CoA
(CHEBI:28493)
has functional parent
coenzyme A
(CHEBI:15346)
deoxycholoyl-CoA
(CHEBI:50111)
has functional parent
coenzyme A
(CHEBI:15346)
farnesoyl-CoA
(CHEBI:28562)
has functional parent
coenzyme A
(CHEBI:15346)
feruloyl-CoA
(CHEBI:14261)
has functional parent
coenzyme A
(CHEBI:15346)
glutaryl-CoA
(CHEBI:15524)
has functional parent
coenzyme A
(CHEBI:15346)
heptanoyl-CoA
(CHEBI:37283)
has functional parent
coenzyme A
(CHEBI:15346)
hexanoyl-CoA
(CHEBI:27540)
has functional parent
coenzyme A
(CHEBI:15346)
icosanoyl-CoA
(CHEBI:15527)
has functional parent
coenzyme A
(CHEBI:15346)
indol-3-ylacetyl-CoA
(CHEBI:12755)
has functional parent
coenzyme A
(CHEBI:15346)
isobutyryl-CoA
(CHEBI:15479)
has functional parent
coenzyme A
(CHEBI:15346)
itaconyl-CoA
(CHEBI:15528)
has functional parent
coenzyme A
(CHEBI:15346)
linoleoyl-CoA
(CHEBI:15530)
has functional parent
coenzyme A
(CHEBI:15346)
malonyl-CoA
(CHEBI:15531)
has functional parent
coenzyme A
(CHEBI:15346)
malonyl-CoA lithium salt
(CHEBI:232859)
has functional parent
coenzyme A
(CHEBI:15346)
methacrylyl-CoA
(CHEBI:27754)
has functional parent
coenzyme A
(CHEBI:15346)
myristoyl-CoA
(CHEBI:15532)
has functional parent
coenzyme A
(CHEBI:15346)
n-propionyl-CoA lithium salt
(CHEBI:233091)
has functional parent
coenzyme A
(CHEBI:15346)
nonanoyl-CoA
(CHEBI:27770)
has functional parent
coenzyme A
(CHEBI:15346)
oleoyl-CoA
(CHEBI:15534)
has functional parent
coenzyme A
(CHEBI:15346)
palmitoyl-CoA
(CHEBI:15525)
has functional parent
coenzyme A
(CHEBI:15346)
pent-2-enoyl-CoA
(CHEBI:27962)
has functional parent
coenzyme A
(CHEBI:15346)
pentanoyl-CoA
(CHEBI:15536)
has functional parent
coenzyme A
(CHEBI:15346)
phenylglyoxylyl-CoA
(CHEBI:50117)
has functional parent
coenzyme A
(CHEBI:15346)
phytanoyl-CoA
(CHEBI:15538)
has functional parent
coenzyme A
(CHEBI:15346)
pimeloyl-CoA
(CHEBI:15504)
has functional parent
coenzyme A
(CHEBI:15346)
propionyl-CoA
(CHEBI:15539)
has functional parent
coenzyme A
(CHEBI:15346)
sinapoyl-CoA
(CHEBI:15540)
has functional parent
coenzyme A
(CHEBI:15346)
succinyl-CoA
(CHEBI:15380)
has functional parent
coenzyme A
(CHEBI:15346)
sulfoacetyl-CoA
(CHEBI:61992)
has functional parent
coenzyme A
(CHEBI:15346)
tetracosanoyl-CoA
(CHEBI:52974)
has functional parent
coenzyme A
(CHEBI:15346)
tetradecenoyl-CoA
(CHEBI:26900)
has functional parent
coenzyme A
(CHEBI:15346)
thiophene-2-carbonyl-CoA
(CHEBI:15542)
has functional parent
coenzyme A
(CHEBI:15346)
vinylacetyl-CoA
(CHEBI:15543)
has functional parent
coenzyme A
(CHEBI:15346)
coenzyme A(4−)
(CHEBI:57287)
is conjugate base of
coenzyme A
(CHEBI:15346)
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3'-phosphoadenosine 5'-{3-[(3R)-3-hydroxy-2,2-dimethyl-4-oxo-4-({3-oxo-3-[(2-sulfanylethyl)amino]propyl}amino)butyl] dihydrogen diphosphate}
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3'-phosphoadenosine-(5')diphospho(4')pantatheine
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ChEBI
|
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[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]methyl (3R)-3-hydroxy-4-({3-oxo-3-[(2-sulfanylethyl)amino]propyl}amino)-2,2-dimethyl-4-oxobutyl dihydrogen diphosphate
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ChEBI
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CoA
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KEGG COMPOUND
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CoA-SH
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KEGG COMPOUND
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CoASH
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ChEBI
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Coenzym A
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ChEBI
|
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Coenzyme A
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KEGG COMPOUND
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COENZYME A
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PDBeChem
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HSCoA
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ChEBI
|
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Koenzym A
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ChEBI
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C00007258
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KNApSAcK
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C00010
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KEGG COMPOUND
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COA
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PDBeChem
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Coenzyme_A
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Wikipedia
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COZ
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PDBeChem
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DB01992
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DrugBank
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| View more database links |
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77809
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Beilstein Registry Number
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Beilstein
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85-61-0
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CAS Registry Number
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ChemIDplus
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Rana A, Seinen E, Siudeja K, Muntendam R, Srinivasan B, van der Want JJ, Hayflick S, Reijngoud DJ, Kayser O, Sibon OC (2010)
Pantethine rescues a Drosophila model for pantothenate kinase-associated neurodegeneration.
Proceedings of the National Academy of Sciences of the United States of America 107, 6988-6993 [PubMed:20351285]
[show Abstract]
Pantothenate kinase-associated neurodegeneration (PKAN), a progressive neurodegenerative disorder, is associated with impairment of pantothenate kinase function. Pantothenate kinase is the first enzyme required for de novo synthesis of CoA, an essential metabolic cofactor. The pathophysiology of PKAN is not understood, and there is no cure to halt or reverse the symptoms of this devastating disease. Recently, we and others presented a PKAN Drosophila model, and we demonstrated that impaired function of pantothenate kinase induces a neurodegenerative phenotype and a reduced lifespan. We have explored this Drosophila model further and have demonstrated that impairment of pantothenate kinase is associated with decreased levels of CoA, mitochondrial dysfunction, and increased protein oxidation. Furthermore, we searched for compounds that can rescue pertinent phenotypes of the Drosophila PKAN model and identified pantethine. Pantethine feeding restores CoA levels, improves mitochondrial function, rescues brain degeneration, enhances locomotor abilities, and increases lifespan. We show evidence for the presence of a de novo CoA biosynthesis pathway in which pantethine is used as a precursor compound. Importantly, this pathway is effective in the presence of disrupted pantothenate kinase function. Our data suggest that pantethine may serve as a starting point to develop a possible treatment for PKAN. | Yokooji Y, Tomita H, Atomi H, Imanaka T (2009)
Pantoate kinase and phosphopantothenate synthetase, two novel enzymes necessary for CoA biosynthesis in the Archaea.
The Journal of biological chemistry 284, 28137-28145 [PubMed:19666462]
[show Abstract]
Bacteria/eukaryotes share a common pathway for coenzyme A (CoA) biosynthesis. Although archaeal genomes harbor homologs for most of these enzymes, homologs of bacterial/eukaryotic pantothenate synthetase (PS) and pantothenate kinase (PanK) are missing. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to produce pantothenate, whereas PanK catalyzes the ATP-dependent phosphorylation of pantothenate to produce 4'-phosphopantothenate. When we examined the cell-free extracts of the hyperthermophilic archaeon Thermococcus kodakaraensis, PanK activity could not be detected. A search for putative kinase-encoding genes widely distributed in Archaea, but not present in bacteria/eukaryotes, led to four candidate genes. Among these genes, TK2141 encoded a protein with relatively low PanK activity. However, higher levels of activity were observed when pantothenate was replaced with pantoate. V(max) values were 7-fold higher toward pantoate, indicating that TK2141 encoded a novel enzyme, pantoate kinase (PoK). A search for genes with a distribution similar to TK2141 led to the identification of TK1686. The protein product catalyzed the ATP-dependent conversion of phosphopantoate and beta-alanine to produce 4'-phosphopantothenate and did not exhibit PS activity, indicating that TK1686 also encoded a novel enzyme, phosphopantothenate synthetase (PPS). Although the classic PS/PanK system performs condensation with beta-alanine prior to phosphorylation, the PoK/PPS system performs condensation after phosphorylation of pantoate. Gene disruption of TK2141 and TK1686 led to CoA auxotrophy, indicating that both genes are necessary for CoA biosynthesis in T. kodakaraensis. Homologs of both genes are widely distributed among the Archaea, suggesting that the PoK/PPS system represents the pathway for 4'-phosphopantothenate biosynthesis in the Archaea. | Bosveld F, Rana A, van der Wouden PE, Lemstra W, Ritsema M, Kampinga HH, Sibon OC (2008)
De novo CoA biosynthesis is required to maintain DNA integrity during development of the Drosophila nervous system.
Human molecular genetics 17, 2058-2069 [PubMed:18407920]
[show Abstract]
In a forward genetic screen in Drosophila melanogaster, aimed to identify genes required for normal locomotor function, we isolated dPPCS (the second enzyme of the Coenzyme A biosynthesis pathway). The entire Drosophila CoA synthesis route was dissected, annotated and additional CoA mutants were obtained (dPANK/fumble) or generated (dPPAT-DPCK). Drosophila CoA mutants suffer from neurodegeneration, altered lipid homeostasis and the larval brains display increased apoptosis. Also, de novo CoA biosynthesis is required to maintain DNA integrity during the development of the central nervous system. In humans, mutations in the PANK2 gene, the first enzyme in the CoA synthesis route, are associated with pantothenate kinase-associated neurodegeneration. Currently, the pathogenesis of this neurodegenerative disease is poorly understood. We provide the first comprehensive analysis of the physiological implications of mutations in the entire CoA biosynthesis route in an animal model system. Surprisingly, our findings reveal a major role of this conserved pathway in maintaining DNA and cellular integrity, explaining how impaired CoA synthesis during CNS development can elicit a neurodegenerative phenotype. | Leonardi R, Zhang YM, Rock CO, Jackowski S (2005)
Coenzyme A: back in action.
Progress in lipid research 44, 125-153 [PubMed:15893380]
[show Abstract]
Coenzyme A (CoA) is a ubiquitous essential cofactor that plays a central role in the metabolism of carboxylic acids, including short- and long-chain fatty acids. In the last few years, all of the genes encoding the CoA biosynthetic enzymes have been identified and the structures of several proteins in the pathway have been determined. CoA is assembled in five steps from pantothenic acid and pathway intermediates are common to both prokaryotes and eukaryotes. In spite of the identical biochemistry, remarkable sequence differences among some of the prokaryotic and eukaryotic enzymes have been revealed by comparative genomics. Renewed interest in CoA has arisen from the realization that the biosynthetic pathway is a target for antibacterial drug discovery and from the unexpected association of a human neurodegenerative disorder with mutations in pantothenate kinase. The purpose of this review is to integrate previous knowledge with the most recent findings in the genetics, enzymology and regulation of CoA biosynthesis in bacteria, plants and mammals. | Genschel U (2004)
Coenzyme A biosynthesis: reconstruction of the pathway in archaea and an evolutionary scenario based on comparative genomics.
Molecular biology and evolution 21, 1242-1251 [PubMed:15014152]
[show Abstract]
Coenzyme A (CoA) holds a central position in cellular metabolism and therefore can be assumed to be an ancient molecule. Starting from the known E. coli and human enzymes required for the biosynthesis of CoA, phylogenetic profiles and chromosomal proximity methods enabled an almost complete reconstruction of archaeal CoA biosynthesis. This includes the identification of strong candidates for archaeal pantothenate synthetase and pantothenate kinase, which are unrelated to the corresponding bacterial or eukaryotic enzymes. According to this reconstruction, the topology of CoA synthesis from common precursors is essentially conserved across the three domains of life. The CoA pathway is conserved to varying degrees in eukaryotic pathogens like Giardia lamblia or Plasmodium falciparum, indicating that these pathogens have individual uptake-mechanisms for different CoA precursors. Phylogenetic analysis and phyletic distribution of the CoA biosynthetic enzymes suggest that the enzymes required for the synthesis of phosphopantothenate were recruited independently in the bacterial and archaeal lineages by convergent evolution, and that eukaryotes inherited the genes for the synthesis of pantothenate (vitamin B5) from bacteria. Homologues to bacterial enzymes involved in pantothenate biosynthesis are present in a subset of archaeal genomes. The phylogenies of these enzymes indicate that they were acquired from bacterial thermophiles through horizontal gene transfer. Monophyly can be inferred for each of the enzymes catalyzing the four ultimate steps of CoA synthesis, the conversion of phosphopantothenate into CoA. The results support the notion that CoA was initially synthesized from a prebiotic precursor, most likely pantothenate or a related compound. | Daugherty M, Polanuyer B, Farrell M, Scholle M, Lykidis A, de Crécy-Lagard V, Osterman A (2002)
Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics.
The Journal of biological chemistry 277, 21431-21439 [PubMed:11923312]
[show Abstract]
The biosynthesis of CoA from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. The CoA biosynthetic genes in bacteria have all recently been identified, but their counterparts in humans and other eukaryotes remained mostly unknown. Using comparative genomics, we have identified human genes encoding the last four enzymatic steps in CoA biosynthesis: phosphopantothenoylcysteine synthetase (EC ), phosphopantothenoylcysteine decarboxylase (EC ), phosphopantetheine adenylyltransferase (EC ), and dephospho-CoA kinase (EC ). Biological functions of these human genes were verified using a complementation system in Escherichia coli based on transposon mutagenesis. The individual human enzymes were overexpressed in E. coli and purified, and the corresponding activities were experimentally verified. In addition, the entire pathway from phosphopantothenate to CoA was successfully reconstituted in vitro using a mixture of purified recombinant enzymes. Human recombinant bifunctional phosphopantetheine adenylyltransferase/dephospho-CoA kinase was kinetically characterized. This enzyme was previously suggested as a point of CoA biosynthesis regulation, and we have observed significant differences in mRNA levels of the corresponding human gene in normal and tumor cells by Northern blot analysis. | Robishaw JD, Neely JR (1985)
Coenzyme A metabolism.
The American journal of physiology 248, E1-9 [PubMed:2981478]
[show Abstract]
The metabolism of coenzyme A and control of its synthesis are reviewed. Pantothenate kinase is an important rate-controlling enzyme in the synthetic pathway of all tissues studied and appears to catalyze the flux-generating reaction of the pathway in cardiac muscle. This enzyme is strongly inhibited by coenzyme A and all of its acyl esters. The cytosolic concentrations of coenzyme A and acetyl coenzyme A in both liver and heart are high enough to totally inhibit pantothenate kinase under all conditions. Free carnitine, but not acetyl carnitine, deinhibits the coenzyme A-inhibited enzyme. Carnitine alone does not increase enzyme activity. Thus changes in the acetyl carnitine-to-carnitine ratio that occur with nutritional states provides a mechanism for regulation of coenzyme A synthetic rates. Changes in the rate of coenzyme A synthesis in liver and heart occurs with fasting, refeeding, and diabetes and in heart muscle with hypertrophy. The pathway and regulation of coenzyme A degradation are not understood. | Mautner HG, Merrill RE, Currier SF, Harvey G (1981)
Interaction of aromatic dyes with the coenzyme A binding site of choline acetyltransferase.
Journal of medicinal chemistry 24, 1534-1537 (Source: ChEMBL) [PubMed:7310833]
[show Abstract]
The interaction of a series of aromatic dyes with the coenzyme A binding site of choline acetyltransferase was studied. Several of the dyes were very potent inhibitors of the enzyme. With few exceptions, inhibition was competitive with respect to acetylcoenzyme A and noncompetitive with respect to choline. It appears likely that inhibition by dyes such as Reactive Blue 2 (Cibacron Blue F3GA) or Congo Red, as in the case of coenzyme A interactions, involves hydrophobic bonding, as well as a coulombic interaction with an arginine residue. | BADDILEY J, THAIN EM, NOVELLI GD, LIPMANN F (1953)
Structure of coenzyme A.
Nature 171, 76 [PubMed:13025483] |
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2024-06-03
