Butyryl-CoA

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.

Butyryl-CoA

Stereo skeletal formula of tetradeprotonated butyryl-coA ({[(2R,3S,4R,5R)-5-yl,-2-meth,-4-hydrox,-3-yl]})
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} 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
Identifiers
CAS Number	2140-48-9 N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:15517
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	C00136 Y
MeSH	butyryl-coenzyme+A
PubChem CID	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]}
CompTox Dashboard (EPA)	DTXSID70943955
InChI 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
SMILES 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
Chemical formula	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). Infobox references

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.

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-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]

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.^[25]

4-aminobutanoate (GABA) degradation

Overview of 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.

Further reading

PubChem. "Butyryl-CoA". pubchem.ncbi.nlm.nih.gov. Retrieved 2021-11-18.

See also

• Acyl-CoA
  • Fatty acyl-CoA esters