Chemistry:Butyryl-CoA

From HandWiki

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]

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.

See also

References

  1. ↑ "Human Metabolome Database: Showing metabocard for Butyryl-CoA (HMDB0001088)". http://www.hmdb.ca/metabolites/HMDB0001088. 
  2. ↑ 2.0 2.1 Li, Fuli; Hinderberger, Julia; Seedorf, Henning; Zhang, Jin; Buckel, Wolfgang; Thauer, Rudolf K. (February 2008). "Coupled Ferredoxin and Crotonyl Coenzyme A (CoA) Reduction with NADH Catalyzed by the Butyryl-CoA Dehydrogenase/Etf Complex from Clostridium kluyveri" (in en). Journal of Bacteriology 190 (3): 843–850. doi:10.1128/JB.01417-07. ISSN 0021-9193. PMID 17993531. 
  3. ↑ "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. February 2013. doi:10.1007/s12010-012-0060-7. PMID 23292245. 
  4. ↑ "Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene". Environmental Microbiology 12 (2): 304–314. February 2010. doi:10.1111/j.1462-2920.2009.02066.x. PMID 19807780. Bibcode: 2010EnvMi..12..304L. 
  5. ↑ "MetaCyc butanoyl-CoA". https://metacyc.org/compound?orgid=META&id=BUTYRYL-COA. 
  6. ↑ Fujita, Yasutaro; Matsuoka, Hiroshi; Hirooka, Kazutake (November 2007). "Regulation of Fatty Acid Metabolism in Bacteria" (in en). Molecular Microbiology 66 (4): 829–839. doi:10.1111/j.1365-2958.2007.05947.x. ISSN 0950-382X. PMID 17919287. https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2007.05947.x. 
  7. ↑ Haapalainen, Antti M.; Meriläinen, Gitte; Pirilä, Päivi L.; Kondo, Naomi; Fukao, Toshiyuki; Wierenga, Rik K. (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, Antti M.; Meriläinen, Gitte; Pirilä, Päivi L.; Kondo, Naomi; Fukao, Toshiyuki; Wierenga, Rik K. (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" (in en). Biochemistry 46 (14): 4305–4321. doi:10.1021/bi6026192. ISSN 0006-2960. PMID 17371050. 
  9. ↑ Nesbitt, Natasha M.; Yang, Xinxin; Fontán, Patricia; Kolesnikova, Irina; Smith, Issar; Sampson, Nicole S.; Dubnau, Eugenie (January 2010). "A Thiolase of Mycobacterium tuberculosis Is Required for Virulence and Production of Androstenedione and Androstadienedione from Cholesterol" (in en). Infection and Immunity 78 (1): 275–282. doi:10.1128/IAI.00893-09. ISSN 0019-9567. PMID 19822655. 
  10. ↑ Stern, J. R.; Coon, M. J.; Del Campillo, A. (1953-01-03). "Enzymatic breakdown and synthesis of acetoacetate". Nature 171 (4340): 28–30. doi:10.1038/171028a0. ISSN 0028-0836. PMID 13025466. Bibcode: 1953Natur.171...28S. 
  11. ↑ Goldman, D. S. (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. ↑ 12.0 12.1 Campbell, John W.; Cronan, John E. (July 2002). "The Enigmatic Escherichia coli fadE Gene Is yafH" (in en). Journal of Bacteriology 184 (13): 3759–3764. doi:10.1128/JB.184.13.3759-3764.2002. ISSN 0021-9193. 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.; Ikeda, Y.; Kraus, 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, J J; Wang, M; Paschke, R (1993-08-15). "Crystal structures of medium-chain acyl-CoA dehydrogenase from pig liver mitochondria with and without substrate." (in en). Proceedings of the National Academy of Sciences 90 (16): 7523–7527. doi:10.1073/pnas.90.16.7523. ISSN 0027-8424. PMID 8356049. Bibcode: 1993PNAS...90.7523K. 
  16. ↑ VANHOOREN, Johannes C. T.; MARYNEN, Peter; MANNAERTS, Guy P.; VAN VELDHOVEN, Paul P. (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. PMID 9271077. PMC 1218600. https://doi.org/10.1042/bj3250593. 
  17. ↑ Willard, Jan; Vicanek, Caroline; Battaile, Kevin P.; Van Veldhoven, Paul P.; Fauq, Abdul H.; Rozen, Rima; Vockley, Jerry (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. https://www.sciencedirect.com/science/article/pii/S0003986196902908. 
  18. ↑ Barker, H. A.; Kamen, M. D.; Bornstein, B. T. (December 1945). "The Synthesis of Butyric and Caproic Acids from Ethanol and Acetic Acid by Clostridium Kluyveri" (in en). Proceedings of the National Academy of Sciences 31 (12): 373–381. doi:10.1073/pnas.31.12.373. ISSN 0027-8424. PMID 16588706. Bibcode: 1945PNAS...31..373B. 
  19. ↑ 19.0 19.1 Bornstein, B. T.; Barker, H. A. (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. ↑ 20.0 20.1 Kenealy, William R.; Waselefsky, David M. (April 1985). "Studies on the substrate range of Clostridium kluyveri; the use of propanol and succinate" (in en). Archives of Microbiology 141 (3): 187–194. doi:10.1007/BF00408056. ISSN 0302-8933. Bibcode: 1985ArMic.141..187K. http://link.springer.com/10.1007/BF00408056. 
  21. ↑ Williamson, G; Engel, P C (1984-03-01). "Butyryl-CoA dehydrogenase from Megasphaera elsdenii . Specificity of the catalytic reaction" (in en). Biochemical Journal 218 (2): 521–529. doi:10.1042/bj2180521. ISSN 0264-6021. PMID 6712628. PMC 1153368. https://portlandpress.com/biochemj/article/218/2/521/17032/Butyryl-CoA-dehydrogenase-from-Megasphaera. 
  22. ↑ Turano, F. J.; Thakkar, S. S.; Fang, T.; Weisemann, J. M. (1997-04-01). "Characterization and Expression of NAD(H)-Dependent Glutamate Dehydrogenase Genes in Arabidopsis" (in en). Plant Physiology 113 (4): 1329–1341. doi:10.1104/pp.113.4.1329. ISSN 1532-2548. PMID 9112779. 
  23. ↑ Rangarajan, Erumbi S.; Li, Yunge; Ajamian, Eunice; Iannuzzi, Pietro; Kernaghan, Stephanie D.; Fraser, Marie E.; Cygler, Miroslaw; Matte, Allan (December 2005). "Crystallographic Trapping of the Glutamyl-CoA Thioester Intermediate of Family I CoA Transferases" (in en). Journal of Biological Chemistry 280 (52): 42919–42928. doi:10.1074/jbc.M510522200. PMID 16253988. 
  24. ↑ Vanderwinkel, Edgard; Furmanski, Philip; Reeves, Henry C.; Ajl, Samuel J. (December 1968). "Growth of Escherichiacoli on fatty acids: Requirement for coenzyme a transferase activity" (in en). Biochemical and Biophysical Research Communications 33 (6): 902–908. doi:10.1016/0006-291X(68)90397-5. PMID 4884054. Bibcode: 1968BBRC...33..902V. https://linkinghub.elsevier.com/retrieve/pii/0006291X68903975. 
  25. ↑ "The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile". Nature Communications 8 (1). November 2017. doi:10.1038/s41467-017-01746-3. PMID 29146947. Bibcode: 2017NatCo...8.1577D. 
  26. ↑ 26.0 26.1 Belitsky, Boris R.; Sonenshein, Abraham L. (July 2002). "GabR, a member of a novel protein family, regulates the utilization of γ -aminobutyrate in Bacillus subtilis" (in en). Molecular Microbiology 45 (2): 569–583. doi:10.1046/j.1365-2958.2002.03036.x. ISSN 0950-382X. PMID 12123465. https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2958.2002.03036.x. 
  27. ↑ Hardman, John K.; Stadtman, Thressa C. (April 1960). "METABOLISM OF ω-AMINO ACIDS: I. Fermentation of γ-Aminobutyric Acid by Clostridium aminobutyricum n. sp." (in en). Journal of Bacteriology 79 (4): 544–548. doi:10.1128/jb.79.4.544-548.1960. ISSN 0021-9193. PMID 14399736. 
  28. ↑ Hardman, J. K.; Stadtman, T. C. (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, Gorm; Andersen, Birgit; Dobritzsch, Doreen; Schnackerz, Klaus D.; Piškur, Jure (April 2007). "A gene duplication led to specialized γ-aminobutyrate and β-alanine aminotransferase in yeast" (in en). The FEBS Journal 274 (7): 1804–1817. doi:10.1111/j.1742-4658.2007.05729.x. ISSN 1742-464X. PMID 17355287. https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2007.05729.x. 
  30. ↑ Gerhardt, Astrid; Çinkaya, Irfan; Linder, Dietmar; Huisman, Gjalt; Buckel, Wolfgang (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. doi:10.1007/s002030000195. ISSN 0302-8933. PMID 11041350. Bibcode: 2000ArMic.174..189G. http://link.springer.com/10.1007/s002030000195. 
  31. ↑ Jakoby, W. B.; Scott, E. M. (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, Ke; Xu, En (2008-06-01). "The role and the mechanism of γ-aminobutyric acid during central nervous system development" (in en). Neuroscience Bulletin 24 (3): 195–200. doi:10.1007/s12264-008-0109-3. ISSN 1995-8218. PMID 18500393. PMC 5552538. https://doi.org/10.1007/s12264-008-0109-3. 
  33. ↑ de Leon, Anthony S.; Tadi, Prasanna (2024), "Biochemistry, Gamma Aminobutyric Acid", StatPearls (Treasure Island (FL): StatPearls Publishing), PMID 31869147, https://www.ncbi.nlm.nih.gov/books/NBK551683/, retrieved 2024-04-14 
  34. ↑ Donahue, Manus J.; Near, Jamie; Blicher, Jakob U.; Jezzard, Peter (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. https://www.sciencedirect.com/science/article/pii/S1053811910009687. 
  35. ↑ Welch, Richard W.; Rudolph, Frederick B.; Papoutsakis, E.Terry (September 1989). "Purification and characterization of the NADH-dependent butanol dehydrogenase from Clostridium acetobutylicum (ATCC 824)" (in en). Archives of Biochemistry and Biophysics 273 (2): 309–318. doi:10.1016/0003-9861(89)90489-X. PMID 2673038. https://linkinghub.elsevier.com/retrieve/pii/000398618990489X. 
  36. ↑ Wiesenborn, D P; Rudolph, F B; Papoutsakis, E T (February 1989). "Phosphotransbutyrylase from Clostridium acetobutylicum ATCC 824 and its role in acidogenesis" (in en). Applied and Environmental Microbiology 55 (2): 317–322. doi:10.1128/aem.55.2.317-322.1989. ISSN 0099-2240. PMID 2719475. Bibcode: 1989ApEnM..55..317W. 
  37. ↑ Wiesenborn, Dennis P.; Rudolph, Frederick B.; Papoutsakis, Eleftherios T. (November 1988). "Thiolase from Clostridium acetobutylicum ATCC 824 and Its Role in the Synthesis of Acids and Solvents" (in en). Applied and Environmental Microbiology 54 (11): 2717–2722. doi:10.1128/aem.54.11.2717-2722.1988. ISSN 0099-2240. PMID 16347774. Bibcode: 1988ApEnM..54.2717W. 
  38. ↑ Stabler, Sally P.; Marcell, Paul D.; Allen, Robert H. (August 1985). "Isolation and characterization of dl-methylmalonyl-coenzyme A racemase from rat liver" (in en). Archives of Biochemistry and Biophysics 241 (1): 252–264. doi:10.1016/0003-9861(85)90381-9. PMID 2862845. https://linkinghub.elsevier.com/retrieve/pii/0003986185903819. 
  39. ↑ Nandi, D. L.; Lucas, S. V.; Webster, L. T. (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. 

Further reading

PubChem. "Butyryl-CoA" (in en). https://pubchem.ncbi.nlm.nih.gov/compound/122283. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Butyryl-CoA&oldid=4032502"