Butyryl-CoA
Names
IUPAC name
3′-O -Phosphonoadenosine 5′-{[(2R ,3S ,4R ,5R )-5-(6-Amino-9H -purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]methyl} O 3 -{(3R )-4-[(3-{[2-(butanoylsulfanyl)ethyl]amino}-3-oxopropyl)amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl dihydrogen diphosphate}
Systematic IUPAC name
O 1 -{[(2R ,3S ,4R ,5R )-5-(6-Amino-9H -purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]methyl} O 3 -{(3R )-4-[(3-{[2-(butanoylsulfanyl)ethyl]amino}-3-oxopropyl)amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl} dihydrogen diphosphate
Identifiers
3DMet
ChEBI
ChemSpider
260 Y
388318 {[(2R ,3S ,4R ,5R )-5-yl,-2-meth,-4-hydrox,-3-yl]} Y
5292369 {[(2R ,3R ,5R )-5-yl,-2-({[{[(3S )-3-hydrox]-ox}-phosph]-ox}-meth),-3-yl]} Y
KEGG
MeSH
butyryl-coenzyme+A
265
25201345 {[(2R ,5R )-5-yl,-2-({[{[(3R )-3-hydrox]-ox}-phosph]-ox}-meth),-3-yl]}
439173 {[(2R ,3S ,4R ,5R )-5-yl,-2-meth,-4-hydrox,-3-yl]}
46907881 {[(2R ,3R ,5R )-5-yl,-2-({[{[(3R )-3-hydrox]-ox}-phosph]-ox}-meth),-3-yl]}
6917112 {[(2R ,3R ,5R )-5-yl,-2-({[{[(3S )-3-hydrox]-ox}-phosph]-ox}-meth),-3-yl]}
InChI=1S/C25H42N7O17P3S/c1-4-5-16(34)53-9-8-27-15(33)6-7-28-23(37)20(36)25(2,3)11-46-52(43,44)49-51(41,42)45-10-14-19(48-50(38,39)40)18(35)24(47-14)32-13-31-17-21(26)29-12-30-22(17)32/h12-14,18-20,24,35-36H,4-11H2,1-3H3,(H,27,33)(H,28,37)(H,41,42)(H,43,44)(H2,26,29,30)(H2,38,39,40)
Y Key: CRFNGMNYKDXRTN-UHFFFAOYSA-N
Y
CCCC(=O)SCCNC(=O)CCNC(=O)C(O)C(C)(C)COP(O)(=O)OP(O)(=O)OCC1OC(C(O)C1OP(O)(O)=O)N1C=NC2=C(N)N=CN=C12
Properties
C 25 H 42 N 7 O 17 P 3 S
Molar mass
837.62 g·mol−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
Chemical compound
Butyryl-CoA (or butyryl-coenzyme A, butanoyl-CoA ) is an
organic
coenzyme A -containing derivative of
butyric acid .
[1] It is a natural product found in many biological pathways, such as fatty acid metabolism (
degradation and
elongation ),
fermentation , and 4-aminobutanoate (GABA) degradation. It mostly participates as an intermediate, a precursor to and converted from crotonyl-CoA.
[2] This interconversion is mediated by butyryl-CoA dehydrogenase.
From redox data, butyryl-CoA dehydrogenase shows little to no activity at pH higher than 7.0. This is important as enzyme midpoint potential is at pH 7.0 and at 25 °C. Therefore, changes above from this value will denature the enzyme.
[3]
Within the human colon, butyrate helps supply energy to the gut epithelium and helps regulate cell responses.
[4]
Butyryl-CoA has a very high calculated potential Gibbs energy, -462.53937 kcal/mol, stored at its bond with CoA.
[5]
Butyryl-CoA interconverts to and from 3-oxohexanoyl-CoA by acetyl-CoA acetyltransferase (or
thiolase ).
[6] In terms of organic chemistry, the reaction is the reverse of a
Claisen condensation .
[7]
[8]
[9]
[10]
[11]
[12] Subsequently butyryl-CoA is converted into crotonyl-CoA. The conversion is catalyzed by electron-transfer flavoprotein 2,3-oxidoreductase.
[13] This enzyme has many synonyms that are
orthologous to each other, including butyryl-CoA dehydrogenase,
[14]
[15]
[16] acyl-CoA dehydrogenase,
[17] acyl-CoA oxidase,
[18] and short-chain 2-methylacyl-CoA dehydrogenase
[19]
Butyryl-CoA is an intermediate of the fermentation pathway found in
Clostridium kluyveri .
[20]
[21]
[22] This species can ferment acetyl-CoA and
succinate into
butanoate , extracting energy through the process.
[21]
[22] The fermentation pathway from ethanol to acetyl-CoA to butanoate is also known as
ABE fermentation .
Overview of fermentation pathways in
Clostridium kluyveri . The red arrow is the succinate fermentation pathway; the blue arrow is the ethanol/acetyl-CoA fermentation pathway, also known as ABE fermentation.
Butyryl-CoA is reduced from
crotonyl-CoA catalyzing by butyryl-CoA dehydrogenase, where two
NADH molecules donate four electrons, with two of them reducing
ferredoxin ([2Fe-2S] cluster) and the other two reducing crotonyl-CoA into butyryl-CoA.
[23]
[24]
[25] Subsequently, butyryl-CoA is converted into butanoate by propionyl-CoA transferase, which transfers the coenzyme-A group onto an
acetate , forming
acetyl-CoA .
[26]
[27]
Conversion from crotonyl-CoA to butyryl-CoA to butanoate
It is essential in reducing ferredoxins in anaerobic bacteria and archaea so that electron transport phosphorylation and substrate-level phosphorylation can occur with increased efficiency.
[28]
4-aminobutanoate (GABA) degradation
Overview of 4-aminobutanoate (GABA) degradation
Butyryl-CoA is also an intermediate found in
4-aminobutanoate (GABA) degradation.
[29]
4-aminobutanoate (GABA) has two fates in this degradation pathway. When discovered in
Acetoanaerobium sticklandii and
Pseudomonas fluorescens , 4-aminobutanoate was converted into
glutamate , which can be deaminated, releasing
ammonium .
[30]
[31]
[32] However, in
Acetoanaerobium sticklandii and Clostridium aminobutyricum , 4-aminobutanoate was converted into
succinate semialdehyde and, through a series of steps via the intermediate of butanoyl-CoA , finally converted into
butanoate .
[33]
[34]
The degradation pathway plays an important role in regulating the concentration of GABA, which is an inhibitory
neurotransmitter that reduces neuronal excitability.
[35] Dysregulation of GABA degradation can lead to imbalances in neurotransmitter levels, contributing to various
neurological disorders such as
epilepsy ,
anxiety , and
depression .
[36]
[37] The reaction mechanism is the same as that in the fermentation pathway, where butyryl-CoA is first reduced from crotonyl-CoA and then converted into butanoate.
[29]
Butyryl-CoA acts upon
butanol dehydrogenase via
competitive inhibition . The adenine moiety can bind butanol dehydrogenase and reduce its activity.
[38] The phosphate moiety of butyryl-CoA is found to have inhibitory activities upon its binding with phosphotransbutyrylase.
[39]
Butyryl-CoA is also believed to have inhibitory effects on
acetyl-CoA acetyltransferase ,
[40] DL-methylmalonyl-CoA racemase,
[41] and
glycine N-acyltransferase ,
[42] however, the specific mechanism remains unknown.
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