Butyryl-CoA explained

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] [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]

Fermentation

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. 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.[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] 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

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] 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.

Regulation

Butyryl-CoA acts upon butanol dehydrogenase via competitive inhibition. The adenine moiety can bind butanol dehydrogenase and reduce its activity.[37] The phosphate moiety of butyryl-CoA is found to have inhibitory activities upon its binding with phosphotransbutyrylase.[38]

Butyryl-CoA is also believed to have inhibitory effects on acetyl-CoA acetyltransferase,[39] DL-methylmalonyl-CoA racemase,[40] and glycine N-acyltransferase,[41] however, the specific mechanism remains unknown.

Further reading

Web site: PubChem. Butyryl-CoA. 2021-11-18. pubchem.ncbi.nlm.nih.gov. en.

See also

Notes and References

  1. Web site: Human Metabolome Database: Showing metabocard for Butyryl-CoA (HMDB0001088) .
  2. 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 . Journal of Bacteriology . en . 190 . 3 . 843–850 . 10.1128/JB.01417-07 . 0021-9193 . 2223550 . 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 . 10.1007/s12010-012-0060-7 . 23292245 . 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 . 10.1111/j.1462-2920.2009.02066.x . 19807780. 2010EnvMi..12..304L .
  5. Web site: MetaCyc butanoyl-CoA . 2024-04-04 . metacyc.org.
  6. Fujita . Yasutaro . Matsuoka . Hiroshi . Hirooka . Kazutake . November 2007 . Regulation of Fatty Acid Metabolism in Bacteria . Molecular Microbiology . en . 66 . 4 . 829–839 . 10.1111/j.1365-2958.2007.05947.x . 17919287 . 0950-382X.
  7. 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 . Infection and Immunity . en . 78 . 1 . 275–282 . 10.1128/IAI.00893-09 . 0019-9567 . 2798224 . 19822655.
  8. 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 . 10.1021/bi6026192 . 0006-2960 . 17371050.
  9. 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, . Biochemistry . en . 46 . 14 . 4305–4321 . 10.1021/bi6026192 . 17371050 . 0006-2960.
  10. 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 . Infection and Immunity . en . 78 . 1 . 275–282 . 10.1128/IAI.00893-09 . 0019-9567 . 2798224 . 19822655.
  11. Stern . J. R. . Coon . M. J. . Del Campillo . A. . 1953-01-03 . Enzymatic breakdown and synthesis of acetoacetate . Nature . 171 . 4340 . 28–30 . 10.1038/171028a0 . 0028-0836 . 13025466. 1953Natur.171...28S .
  12. 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 . 10.1016/S0021-9258(18)65653-4 . free . 0021-9258 . 13174544.
  13. Campbell . John W. . Cronan . John E. . July 2002 . The Enigmatic Escherichia coli fadE Gene Is yafH . Journal of Bacteriology . en . 184 . 13 . 3759–3764 . 10.1128/JB.184.13.3759-3764.2002 . 0021-9193 . 135136 . 12057976.
  14. Campbell . John W. . Cronan . John E. . July 2002 . The Enigmatic Escherichia coli fadE Gene Is yafH . Journal of Bacteriology . en . 184 . 13 . 3759–3764 . 10.1128/JB.184.13.3759-3764.2002 . 0021-9193 . 135136 . 12057976.
  15. 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 . 10.1016/S0021-9258(20)71245-7 . free . 0021-9258 . 3968063.
  16. Matsubara . Y. . Indo . Y. . Naito . E. . Ozasa . H. . Glassberg . R. . Vockley . J. . Ikeda . Y. . Kraus . J. . Tanaka . K. . 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 . 10.1016/S0021-9258(18)71624-4 . free . 0021-9258 . 2777793.
  17. 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. . Proceedings of the National Academy of Sciences . en . 90 . 16 . 7523–7527 . 10.1073/pnas.90.16.7523 . free . 0027-8424 . 47174 . 8356049. 1993PNAS...90.7523K .
  18. 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 . 10.1042/bj3250593 . 0264-6021 . 1218600 . 9271077.
  19. 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 . 10.1006/abbi.1996.0290 . 8660691 . 0003-9861.
  20. 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 . Proceedings of the National Academy of Sciences . en . 31 . 12 . 373–381 . 10.1073/pnas.31.12.373 . free . 0027-8424 . 1078850 . 16588706. 1945PNAS...31..373B .
  21. 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 . 10.1016/S0021-9258(19)52752-1 . free . 0021-9258 . 18901185.
  22. Kenealy . William R. . Waselefsky . David M. . April 1985 . Studies on the substrate range of Clostridium kluyveri; the use of propanol and succinate . Archives of Microbiology . en . 141 . 3 . 187–194 . 10.1007/BF00408056 . 1985ArMic.141..187K . 0302-8933.
  23. 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 . Journal of Bacteriology . en . 190 . 3 . 843–850 . 10.1128/JB.01417-07 . 0021-9193 . 2223550 . 17993531.
  24. Williamson . G . Engel . P C . 1984-03-01 . Butyryl-CoA dehydrogenase from Megasphaera elsdenii . Specificity of the catalytic reaction . Biochemical Journal . en . 218 . 2 . 521–529 . 10.1042/bj2180521 . 0264-6021 . 1153368 . 6712628.
  25. 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 . Plant Physiology . en . 113 . 4 . 1329–1341 . 10.1104/pp.113.4.1329 . 1532-2548 . 158256 . 9112779.
  26. 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 . Journal of Biological Chemistry . en . 280 . 52 . 42919–42928 . 10.1074/jbc.M510522200. free . 16253988 .
  27. Vanderwinkel . Edgard . Furmanski . Philip . Reeves . Henry C. . Ajl . Samuel J. . December 1968 . Growth of Escherichiacoli on fatty acids: Requirement for coenzyme a transferase activity . Biochemical and Biophysical Research Communications . en . 33 . 6 . 902–908 . 10.1016/0006-291X(68)90397-5. 4884054 .
  28. 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 . 2017NatCo...8.1577D . 10.1038/s41467-017-01746-3 . 5691135 . 29146947.
  29. 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 . Molecular Microbiology . en . 45 . 2 . 569–583 . 10.1046/j.1365-2958.2002.03036.x . 12123465 . 0950-382X.
  30. Hardman . John K. . Stadtman . Thressa C. . April 1960 . METABOLISM OF ω-AMINO ACIDS: I. Fermentation of γ-Aminobutyric Acid by Clostridium aminobutyricum n. sp. . Journal of Bacteriology . en . 79 . 4 . 544–548 . 10.1128/jb.79.4.544-548.1960 . 0021-9193 . 278728 . 14399736.
  31. 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 . 10.1016/S0021-9258(18)67943-8 . free . 0021-9258 . 13952769.
  32. 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 . The FEBS Journal . en . 274 . 7 . 1804–1817 . 10.1111/j.1742-4658.2007.05729.x . 17355287 . 1742-464X.
  33. 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 . 10.1007/s002030000195 . 11041350 . 2000ArMic.174..189G . 0302-8933.
  34. Jakoby . W. B. . Scott . E. M. . April 1959 . Aldehyde oxidation. III. Succinic semialdehyde dehydrogenase . The Journal of Biological Chemistry . 234 . 4 . 937–940 . 10.1016/S0021-9258(18)70207-X . free . 0021-9258 . 13654295.
  35. Li . Ke . Xu . En . 2008-06-01 . The role and the mechanism of γ-aminobutyric acid during central nervous system development . Neuroscience Bulletin . en . 24 . 3 . 195–200 . 10.1007/s12264-008-0109-3 . 1995-8218 . 5552538 . 18500393.
  36. Donahue . Manus J. . Near . Jamie . Blicher . Jakob U. . Jezzard . Peter . 2010-11-01 . Baseline GABA concentration and fMRI response . NeuroImage . 53 . 2 . 392–398 . 10.1016/j.neuroimage.2010.07.017 . 20633664 . 1053-8119.
  37. 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) . Archives of Biochemistry and Biophysics . en . 273 . 2 . 309–318 . 10.1016/0003-9861(89)90489-X. 2673038 .
  38. Wiesenborn . D P . Rudolph . F B . Papoutsakis . E T . February 1989 . Phosphotransbutyrylase from Clostridium acetobutylicum ATCC 824 and its role in acidogenesis . Applied and Environmental Microbiology . en . 55 . 2 . 317–322 . 10.1128/aem.55.2.317-322.1989 . 0099-2240 . 184108 . 2719475. 1989ApEnM..55..317W .
  39. 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 . Applied and Environmental Microbiology . en . 54 . 11 . 2717–2722 . 10.1128/aem.54.11.2717-2722.1988 . 0099-2240 . 204361 . 16347774. 1988ApEnM..54.2717W .
  40. Stabler . Sally P. . Marcell . Paul D. . Allen . Robert H. . August 1985 . Isolation and characterization of dl-methylmalonyl-coenzyme A racemase from rat liver . Archives of Biochemistry and Biophysics . en . 241 . 1 . 252–264 . 10.1016/0003-9861(85)90381-9. 2862845 .
  41. 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 . 10.1016/S0021-9258(18)50309-4 . free . 0021-9258 . 457678.

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