Butyryl-CoA
Chemical compound (organic coenzyme)
From Wikipedia, the free encyclopedia
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.
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| 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} O3-{(3R)-4-[(3-{[2-(butanoylsulfanyl)ethyl]amino}-3-oxopropyl)amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl dihydrogen diphosphate} | |
| Systematic IUPAC name
O1-{[(2R,3S,4R,5R)-5-(6-Amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]methyl} O3-{(3R)-4-[(3-{[2-(butanoylsulfanyl)ethyl]amino}-3-oxopropyl)amino]-3-hydroxy-2,2-dimethyl-4-oxobutyl} dihydrogen diphosphate | |
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3D model (JSmol) |
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| ChEBI | |
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| KEGG | |
| MeSH | butyryl-coenzyme+A |
PubChem CID |
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CompTox Dashboard (EPA) |
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| Properties | |
| C25H42N7O17P3S | |
| 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).
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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]
Reaction
Fatty acid metabolism
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] Subsequently butyryl-CoA is converted into crotonyl-CoA. The conversion is catalyzed by electron-transfer flavoprotein 2,3-oxidoreductase.[12] This enzyme has many synonyms that are orthologous to each other, including butyryl-CoA dehydrogenase,[12][13][14] acyl-CoA dehydrogenase,[15] acyl-CoA oxidase,[16] and short-chain 2-methylacyl-CoA dehydrogenase[17]
Fermentation
Butyryl-CoA is an intermediate of the fermentation pathway found in Clostridium kluyveri.[18][19][20] This species can ferment acetyl-CoA and succinate into butanoate, extracting energy through the process.[19][20] The fermentation pathway from ethanol to acetyl-CoA to butanoate is also known as ABE fermentation.
Butyryl-CoA is reduced from crotonyl-CoAcatalyzing 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.[2][21][22] Subsequently, butyryl-CoA is converted into butanoate by propionyl-CoA transferase, which transfers the coenzyme-A group onto an acetate, forming acetyl-CoA.[23][24]
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.[25]
4-Aminobutanoate (GABA) degradation
Butyryl-CoA is also an intermediate found in 4-aminobutanoate (GABA) degradation.[26] 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.[27][28][29] 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.[30][31]
The degradation pathway plays an important role in regulating the concentration of GABA, which is an inhibitory neurotransmitter that reduces neuronal excitability.[32] Dysregulation of GABA degradation can lead to imbalances in neurotransmitter levels, contributing to various neurological disorders such as epilepsy, anxiety, and depression.[33][34] 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.[26]
Regulation
Butyryl-CoA acts upon butanol dehydrogenase via competitive inhibition. The adenine moiety can bind butanol dehydrogenase and reduce its activity.[35] The phosphate moiety of butyryl-CoA is found to have inhibitory activities upon its binding with phosphotransbutyrylase.[36]
Butyryl-CoA is also believed to have inhibitory effects on acetyl-CoA acetyltransferase,[37] DL-methylmalonyl-CoA racemase,[38] and glycine N-acyltransferase,[39] however, the specific mechanism remains unknown.