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Butyryl-CoA

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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
3D model (JSmol)
3DMet
ChEBI
ChemSpider
  • 260 checkY
  • 388318 {[(2R,3S,4R,5R)-5-yl,-2-meth,-4-hydrox,-3-yl]} checkY
  • 5292369 {[(2R,3R,5R)-5-yl,-2-({[{[(3S)-3-hydrox]-ox}-phosph]-ox}-meth),-3-yl]} checkY
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) checkY
    Key: CRFNGMNYKDXRTN-UHFFFAOYSA-N checkY
  • 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
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).

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

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Fatty acid metabolism

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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

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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

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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

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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

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

See also

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References

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  1. ^ "Human Metabolome Database: Showing metabocard for Butyryl-CoA (HMDB0001088)".
  2. ^ a b Li F, Hinderberger J, Seedorf H, Zhang J, Buckel W, Thauer RK (February 2008). "Coupled Ferredoxin and Crotonyl Coenzyme A (CoA) Reduction with NADH Catalyzed by the Butyryl-CoA Dehydrogenase/Etf Complex from Clostridium kluyveri". Journal of Bacteriology. 190 (3): 843–850. doi:10.1128/JB.01417-07. ISSN 0021-9193. PMC 2223550. PMID 17993531.
  3. ^ Berzin V, Tyurin M, Kiriukhin M (February 2013). "Selective n-butanol production by Clostridium sp. MTButOH1365 during continuous synthesis gas fermentation due to expression of synthetic thiolase, 3-hydroxy butyryl-CoA dehydrogenase, crotonase, butyryl-CoA dehydrogenase, butyraldehyde dehydrogenase, and NAD-dependent butanol dehydrogenase". Applied Biochemistry and Biotechnology. 169 (3): 950–959. doi:10.1007/s12010-012-0060-7. PMID 23292245. S2CID 22534861.
  4. ^ Louis P, Young P, Holtrop G, Flint HJ (February 2010). "Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene". Environmental Microbiology. 12 (2): 304–314. Bibcode:2010EnvMi..12..304L. doi:10.1111/j.1462-2920.2009.02066.x. PMID 19807780.
  5. ^ "MetaCyc butanoyl-CoA". metacyc.org. Retrieved 2024-04-04.
  6. ^ Fujita Y, Matsuoka H, Hirooka K (November 2007). "Regulation of Fatty Acid Metabolism in Bacteria". Molecular Microbiology. 66 (4): 829–839. doi:10.1111/j.1365-2958.2007.05947.x. ISSN 0950-382X. PMID 17919287.
  7. ^ Haapalainen AM, Meriläinen G, Pirilä PL, Kondo N, Fukao T, Wierenga RK (2007-04-10). "Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function". Biochemistry. 46 (14): 4305–4321. doi:10.1021/bi6026192. ISSN 0006-2960. PMID 17371050.
  8. ^ Haapalainen AM, Meriläinen G, Pirilä PL, Kondo N, Fukao T, Wierenga RK (2007-03-20). "Crystallographic and Kinetic Studies of Human Mitochondrial Acetoacetyl-CoA Thiolase: The Importance of Potassium and Chloride Ions for Its Structure and Function,". Biochemistry. 46 (14): 4305–4321. doi:10.1021/bi6026192. ISSN 0006-2960. PMID 17371050.
  9. ^ Nesbitt NM, Yang X, Fontán P, Kolesnikova I, Smith I, Sampson NS, et al. (January 2010). "A Thiolase of Mycobacterium tuberculosis Is Required for Virulence and Production of Androstenedione and Androstadienedione from Cholesterol". Infection and Immunity. 78 (1): 275–282. doi:10.1128/IAI.00893-09. ISSN 0019-9567. PMC 2798224. PMID 19822655.
  10. ^ Stern JR, Coon MJ, Del Campillo A (1953-01-03). "Enzymatic breakdown and synthesis of acetoacetate". Nature. 171 (4340): 28–30. Bibcode:1953Natur.171...28S. doi:10.1038/171028a0. ISSN 0028-0836. PMID 13025466.
  11. ^ Goldman DS (May 1954). "Studies on the fatty acid oxidizing system of animal tissues. VII. The beta-ketoacyl coenzyme A cleavage enzyme". The Journal of Biological Chemistry. 208 (1): 345–357. doi:10.1016/S0021-9258(18)65653-4. ISSN 0021-9258. PMID 13174544.
  12. ^ a b Campbell JW, Cronan JE (July 2002). "The Enigmatic Escherichia coli fadE Gene Is yafH". Journal of Bacteriology. 184 (13): 3759–3764. doi:10.1128/JB.184.13.3759-3764.2002. ISSN 0021-9193. PMC 135136. PMID 12057976.
  13. ^ Ikeda Y, Okamura-Ikeda K, Tanaka K (1985-01-25). "Purification and characterization of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases from rat liver mitochondria. Isolation of the holo- and apoenzymes and conversion of the apoenzyme to the holoenzyme". The Journal of Biological Chemistry. 260 (2): 1311–1325. doi:10.1016/S0021-9258(20)71245-7. ISSN 0021-9258. PMID 3968063.
  14. ^ Matsubara Y, Indo Y, Naito E, Ozasa H, Glassberg R, Vockley J, et al. (1989-09-25). "Molecular cloning and nucleotide sequence of cDNAs encoding the precursors of rat long chain acyl-coenzyme A, short chain acyl-coenzyme A, and isovaleryl-coenzyme A dehydrogenases. Sequence homology of four enzymes of the acyl-CoA dehydrogenase family". The Journal of Biological Chemistry. 264 (27): 16321–16331. doi:10.1016/S0021-9258(18)71624-4. ISSN 0021-9258. PMID 2777793.
  15. ^ Kim JJ, Wang M, Paschke R (1993-08-15). "Crystal structures of medium-chain acyl-CoA dehydrogenase from pig liver mitochondria with and without substrate". Proceedings of the National Academy of Sciences. 90 (16): 7523–7527. Bibcode:1993PNAS...90.7523K. doi:10.1073/pnas.90.16.7523. ISSN 0027-8424. PMC 47174. PMID 8356049.
  16. ^ VANHOOREN JC, MARYNEN P, MANNAERTS GP, VAN VELDHOVEN PP (1997-08-01). "Evidence for the existence of a pristanoyl-CoA oxidase gene in man". Biochemical Journal. 325 (3): 593–599. doi:10.1042/bj3250593. ISSN 0264-6021. PMC 1218600. PMID 9271077.
  17. ^ Willard J, Vicanek C, Battaile KP, Van Veldhoven PP, Fauq AH, Rozen R, et al. (1996-07-01). "Cloning of a cDNA for Short/Branched Chain Acyl-Coenzyme A Dehydrogenase from Rat and Characterization of Its Tissue Expression and Substrate Specificity". Archives of Biochemistry and Biophysics. 331 (1): 127–133. doi:10.1006/abbi.1996.0290. ISSN 0003-9861. PMID 8660691.
  18. ^ Barker HA, Kamen MD, Bornstein BT (December 1945). "The Synthesis of Butyric and Caproic Acids from Ethanol and Acetic Acid by Clostridium Kluyveri". Proceedings of the National Academy of Sciences. 31 (12): 373–381. Bibcode:1945PNAS...31..373B. doi:10.1073/pnas.31.12.373. ISSN 0027-8424. PMC 1078850. PMID 16588706.
  19. ^ a b Bornstein BT, Barker HA (February 1948). "The energy metabolism of Clostridium kluyveri and the synthesis of fatty acids". The Journal of Biological Chemistry. 172 (2): 659–669. doi:10.1016/S0021-9258(19)52752-1. ISSN 0021-9258. PMID 18901185.
  20. ^ a b Kenealy WR, Waselefsky DM (April 1985). "Studies on the substrate range of Clostridium kluyveri; the use of propanol and succinate". Archives of Microbiology. 141 (3): 187–194. Bibcode:1985ArMic.141..187K. doi:10.1007/BF00408056. ISSN 0302-8933.
  21. ^ Williamson G, Engel PC (1984-03-01). "Butyryl-CoA dehydrogenase from Megasphaera elsdenii . Specificity of the catalytic reaction". Biochemical Journal. 218 (2): 521–529. doi:10.1042/bj2180521. ISSN 0264-6021. PMC 1153368. PMID 6712628.
  22. ^ Turano FJ, Thakkar SS, Fang T, Weisemann JM (1997-04-01). "Characterization and Expression of NAD(H)-Dependent Glutamate Dehydrogenase Genes in Arabidopsis". Plant Physiology. 113 (4): 1329–1341. doi:10.1104/pp.113.4.1329. ISSN 1532-2548. PMC 158256. PMID 9112779.
  23. ^ Rangarajan ES, Li Y, Ajamian E, Iannuzzi P, Kernaghan SD, Fraser ME, et al. (December 2005). "Crystallographic Trapping of the Glutamyl-CoA Thioester Intermediate of Family I CoA Transferases". Journal of Biological Chemistry. 280 (52): 42919–42928. doi:10.1074/jbc.M510522200. PMID 16253988.
  24. ^ Vanderwinkel E, Furmanski P, Reeves HC, Ajl SJ (December 1968). "Growth of Escherichiacoli on fatty acids: Requirement for coenzyme a transferase activity". Biochemical and Biophysical Research Communications. 33 (6): 902–908. doi:10.1016/0006-291X(68)90397-5. PMID 4884054.
  25. ^ Demmer JK, Pal Chowdhury N, Selmer T, Ermler U, Buckel W (November 2017). "The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile". Nature Communications. 8 (1): 1577. Bibcode:2017NatCo...8.1577D. doi:10.1038/s41467-017-01746-3. PMC 5691135. PMID 29146947.
  26. ^ a b Belitsky BR, Sonenshein AL (July 2002). "GabR, a member of a novel protein family, regulates the utilization of γ -aminobutyrate in Bacillus subtilis". Molecular Microbiology. 45 (2): 569–583. doi:10.1046/j.1365-2958.2002.03036.x. ISSN 0950-382X. PMID 12123465.
  27. ^ Hardman JK, Stadtman TC (April 1960). "METABOLISM OF ω-AMINO ACIDS: I. Fermentation of γ-Aminobutyric Acid by Clostridium aminobutyricum n. sp". Journal of Bacteriology. 79 (4): 544–548. doi:10.1128/jb.79.4.544-548.1960. ISSN 0021-9193. PMC 278728. PMID 14399736.
  28. ^ Hardman JK, Stadtman TC (June 1963). "Metabolism of amega-amino acids. III. Mechanism of conversion of gamma-aminobutyrate to gamma-hydroxybutryate by Clostridium aminobutyricum". The Journal of Biological Chemistry. 238 (6): 2081–2087. doi:10.1016/S0021-9258(18)67943-8. ISSN 0021-9258. PMID 13952769.
  29. ^ Andersen G, Andersen B, Dobritzsch D, Schnackerz KD, Piškur J (April 2007). "A gene duplication led to specialized γ-aminobutyrate and β-alanine aminotransferase in yeast". The FEBS Journal. 274 (7): 1804–1817. doi:10.1111/j.1742-4658.2007.05729.x. ISSN 1742-464X. PMID 17355287.
  30. ^ Gerhardt A, Çinkaya I, Linder D, Huisman G, Buckel W (2000-08-30). "Fermentation of 4-aminobutyrate by Clostridium aminobutyricum : cloning of two genes involved in the formation and dehydration of 4-hydroxybutyryl-CoA". Archives of Microbiology. 174 (3): 189–199. Bibcode:2000ArMic.174..189G. doi:10.1007/s002030000195. ISSN 0302-8933. PMID 11041350.
  31. ^ Jakoby WB, Scott EM (April 1959). "Aldehyde oxidation. III. Succinic semialdehyde dehydrogenase". The Journal of Biological Chemistry. 234 (4): 937–940. doi:10.1016/S0021-9258(18)70207-X. ISSN 0021-9258. PMID 13654295.
  32. ^ Li K, Xu E (2008-06-01). "The role and the mechanism of γ-aminobutyric acid during central nervous system development". Neuroscience Bulletin. 24 (3): 195–200. doi:10.1007/s12264-008-0109-3. ISSN 1995-8218. PMC 5552538. PMID 18500393.
  33. ^ de Leon AS, Tadi P (2024), "Biochemistry, Gamma Aminobutyric Acid", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 31869147, retrieved 2024-04-14
  34. ^ Donahue MJ, Near J, Blicher JU, Jezzard P (2010-11-01). "Baseline GABA concentration and fMRI response". NeuroImage. 53 (2): 392–398. doi:10.1016/j.neuroimage.2010.07.017. ISSN 1053-8119. PMID 20633664.
  35. ^ Welch RW, Rudolph FB, Papoutsakis E (September 1989). "Purification and characterization of the NADH-dependent butanol dehydrogenase from Clostridium acetobutylicum (ATCC 824)". Archives of Biochemistry and Biophysics. 273 (2): 309–318. doi:10.1016/0003-9861(89)90489-X. PMID 2673038.
  36. ^ Wiesenborn DP, Rudolph FB, Papoutsakis ET (February 1989). "Phosphotransbutyrylase from Clostridium acetobutylicum ATCC 824 and its role in acidogenesis". Applied and Environmental Microbiology. 55 (2): 317–322. Bibcode:1989ApEnM..55..317W. doi:10.1128/aem.55.2.317-322.1989. ISSN 0099-2240. PMC 184108. PMID 2719475.
  37. ^ Wiesenborn DP, Rudolph FB, Papoutsakis ET (November 1988). "Thiolase from Clostridium acetobutylicum ATCC 824 and Its Role in the Synthesis of Acids and Solvents". Applied and Environmental Microbiology. 54 (11): 2717–2722. Bibcode:1988ApEnM..54.2717W. doi:10.1128/aem.54.11.2717-2722.1988. ISSN 0099-2240. PMC 204361. PMID 16347774.
  38. ^ Stabler SP, Marcell PD, Allen RH (August 1985). "Isolation and characterization of dl-methylmalonyl-coenzyme A racemase from rat liver". Archives of Biochemistry and Biophysics. 241 (1): 252–264. doi:10.1016/0003-9861(85)90381-9. PMID 2862845.
  39. ^ Nandi DL, Lucas SV, Webster LT (1979-08-10). "Benzoyl-coenzyme A:glycine N-acyltransferase and phenylacetyl-coenzyme A:glycine N-acyltransferase from bovine liver mitochondria. Purification and characterization". The Journal of Biological Chemistry. 254 (15): 7230–7237. doi:10.1016/S0021-9258(18)50309-4. ISSN 0021-9258. PMID 457678.
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