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Record Information
Version2.0
Creation Date2009-07-05 03:12:29 UTC
Update Date2014-12-24 20:25:42 UTC
Accession NumberT3D2562
Identification
Common NameGamma-Butyrolactone
ClassSmall Molecule
DescriptionOne of the furans with a carbonyl thereby forming a cyclic lactone. It is an endogenous compound made from gamma-aminobutyrate and is the precursor of gamma-hydroxybutyrate. It is also used as a pharmacological agent and solvent.
Compound Type
  • Ester
  • Ether
  • Food Toxin
  • Household Toxin
  • Indicator and Reagent
  • Industrial/Workplace Toxin
  • Metabolite
  • Organic Compound
  • Solvent
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1,4-Butanolide
1,4-Lactone
1-Oxacyclopentan-2-one
2,3,4,5-Tetrahydro-2-furanone
2-Oxolanone
2-Oxotetrahydrofuran
4,5-Dihydro-2(3H)-furanone
4-Butanolide
4-Deoxytetronate
4-Deoxytetronic acid
4-Hydroxy-Butanoate
4-Hydroxy-Butanoic acid
4-Hydroxy-Butanoic acid g-lactone
4-Hydroxybutanoate
4-Hydroxybutanoic acid
4-Hydroxybutanoic acid lactone
4-Hydroxybutyric acid lactone
Butyric acid lactone
Butyrolactone
Dihydro-2(3H)-furanone
dihydrofuran-2(3h)-one
g-Butalactone
g-Butyrolactone
g-Butyryllactone
g-Hydroxybutyric acid lactone
gamma-Butalactone
gamma-Butyrolactone
gamma-Butyryllactone
gamma-Hydroxybutyric acid lactone
GBL
Paint Clean G
Tetrahydro-2-furanone
γ-Butyrolactone
Chemical FormulaC4H6O2
Average Molecular Mass86.089 g/mol
Monoisotopic Mass86.037 g/mol
CAS Registry Number96-48-0
IUPAC Nameoxolan-2-one
Traditional Namebutyrolactone
SMILESO=C1CCCO1
InChI IdentifierInChI=1S/C4H6O2/c5-4-2-1-3-6-4/h1-3H2
InChI KeyInChIKey=YEJRWHAVMIAJKC-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as gamma butyrolactones. Gamma butyrolactones are compounds containing a gamma butyrolactone moiety, which consists of an aliphatic five-member ring with four carbon atoms, one oxygen atom, and bears a ketone group on the carbon adjacent to the oxygen atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactones
Sub ClassGamma butyrolactones
Direct ParentGamma butyrolactones
Alternative Parents
Substituents
  • Gamma butyrolactone
  • Tetrahydrofuran
  • Carboxylic acid ester
  • Oxacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Neuron
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceColorless oily liquid (18).
Experimental Properties
PropertyValue
Melting Point-45°C
Boiling PointNot Available
Solubility1000.0 mg/mL
LogP-0.64
Predicted Properties
PropertyValueSource
Water Solubility238 g/LALOGPS
logP-0.11ALOGPS
logP0.15ChemAxon
logS0.44ALOGPS
pKa (Strongest Basic)-7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area26.3 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity20.31 m³·mol⁻¹ChemAxon
Polarizability8.23 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004l-9000000000-500445dc73cb69119e6bJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-9000000000-c2f6d51e7b2f9ce1e9f1JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-002f-9000000000-d3df175d3315ed446e14JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-004l-9000000000-500445dc73cb69119e6bJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0006-9000000000-c2f6d51e7b2f9ce1e9f1JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-002f-9000000000-d3df175d3315ed446e14JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-002f-9000000000-bd4b413f20907d13a107JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-9000000000-4a6de93563809aa51a33JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-000i-9000000000-4a6de93563809aa51a33JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-000i-9000000000-b5163f6eb1e8004e61a9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-7M) , Positivesplash10-004l-9000000000-1066d349a6023c66dd64JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (JEOL JMS-D-3000) , Positivesplash10-0006-9000000000-c2f6d51e7b2f9ce1e9f1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80B) , Positivesplash10-002f-9000000000-d3df175d3315ed446e14JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-9000000000-507998514018a44c4cf0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000l-9000000000-d4ec4947321dfb11fab4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-b2a1436205f5365513b0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-9000000000-fb7c9ada825a0c62979fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000l-9000000000-95fda8a898d02f7e71ffJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000l-9000000000-c8282365f175b61ca8c0JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-004l-9000000000-2fc3f4165b5808b41e93JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureInhalation (2) ; oral (2) ; injection (2) ; dermal (2).
Mechanism of ToxicityGamma-butyrolactone is rapidly converted to gamma-hydroxybutyrate. This may account for the subsequent central nervous system depressant. Gamma-butyrolactone is an anesthetic that causes a selective increase in brain dopamine by antagonizing transmitter release from nerve terminal. It is also an endogenous brain metabolite that may be derived from glutamate through gamma-aminobutyrate. GBL binds to the picrotoxin receptor (3, 1).
MetabolismGamma-Butyrolactone undergoes rapid and quantitative conversion by lactonases, yielding gamma-hydroxybutyric acid (4).
Toxicity ValuesLD50: 17.2 mL/kg (Oral, Rat) (581)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (17)
Uses/SourcesCommon solvent and reagent in chemistry and is used as an aroma compound, as a stain remover, as a superglue remover, as a paint stripper, and as a solvent in some wet aluminium electrolytic capacitors (18).
Minimum Risk LevelNot Available
Health EffectsCNS depression; amnesia and hypotonia. Rarely, hypertension, orthostatic hypotension, apnea, dyskinesias, dystonias, and hypomania occur.
SymptomsHeadache, confusion, ataxia, urinary incontinence or urgency, difficulty breathing, bradycardia, uncontrollable shaking, hallucinations, seizure-like activity (uncontrollable or unusual movements), and acidosis. Hypothermia has been reported in adults and children following exposure (13).
TreatmentIn case of oral exposure, administer a benzodiazepine IV. There is no antidote. Treatment is symptomatic and supportive. (13)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB04699
HMDB IDHMDB00549
PubChem Compound ID7302
ChEMBL IDCHEMBL95681
ChemSpider ID7029
KEGG IDC01770
UniProt IDNot Available
OMIM ID
ChEBI ID42639
BioCyc IDCPD-10135
CTD IDD015107
Stitch IDButyrolactone, gamma-
PDB IDGBL
ACToR ID227
Wikipedia Link4-Hydroxybutyric acid lactone
References
Synthesis Reference

Fabio Giannessi, Maria Ornella Tinti, Francesco De Angelis, “Process for producing®-3-hydroxy-4-butyrolactone useful for preparing®-carnitine.” U.S. Patent US6127552, issued February, 1998.

MSDSLink
General References
  1. Holland KD, Yoon KW, Ferrendelli JA, Covey DF, Rothman SM: Gamma-butyrolactone antagonism of the picrotoxin receptor: comparison of a pure antagonist and a mixed antagonist/inverse agonist. Mol Pharmacol. 1991 Jan;39(1):79-84. [1846222 ]
  2. McMahon LR, Cunningham KA: Role of 5-HT(2a) and 5-HT(2B/2C) receptors in the behavioral interactions between serotonin and catecholamine reuptake inhibitors. Neuropsychopharmacology. 2001 Mar;24(3):319-29. [11166521 ]
  3. Zhang M, Hu P, Krois CR, Kane MA, Napoli JL: Altered vitamin A homeostasis and increased size and adiposity in the rdh1-null mouse. FASEB J. 2007 Sep;21(11):2886-96. Epub 2007 Apr 13. [17435174 ]
  4. Winter JC, Fiorella DJ, Helsley SE, Rabin RA: Partial generalization of (-)DOM to fluvoxamine in the rat: implications for SSRI-induced mania and psychosis. Int J Neuropsychopharmacol. 1999 Sep;2(3):165-172. [11281985 ]
  5. Fukui Y, Matsusima E, Muramoto K, Nagai N, Ohama K, Yamashita K: Validation of a simple gas chromatographic-mass spectrometric method for the determination of gamma-butyrolactone in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Feb 25;785(1):73-80. [12535840 ]
  6. Thupari JN, Landree LE, Ronnett GV, Kuhajda FP: C75 increases peripheral energy utilization and fatty acid oxidation in diet-induced obesity. Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9498-502. Epub 2002 Jun 11. [12060712 ]
  7. Wood M, Laloup M, Samyn N, Morris MR, de Bruijn EA, Maes RA, Young MS, Maes V, De Boeck G: Simultaneous analysis of gamma-hydroxybutyric acid and its precursors in urine using liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2004 Nov 12;1056(1-2):83-90. [15595536 ]
  8. Quintanilla RA, Orellana DI, Gonzalez-Billault C, Maccioni RB: Interleukin-6 induces Alzheimer-type phosphorylation of tau protein by deregulating the cdk5/p35 pathway. Exp Cell Res. 2004 Apr 15;295(1):245-57. [15051507 ]
  9. Knust U, Hull WE, Spiegelhalder B, Bartsch H, Strowitzki T, Owen RW: Analysis of enterolignan glucuronides in serum and urine by HPLC-ESI-MS. Food Chem Toxicol. 2006 Jul;44(7):1038-49. Epub 2006 Feb 20. [16488523 ]
  10. Selmaoui B, Aymard N, Lambrozo J, Touitou Y: Evaluation of the nocturnal levels of urinary biogenic amines in men exposed overnight to 50-Hz magnetic field. Life Sci. 2003 Oct 31;73(24):3073-82. [14550848 ]
  11. Oshima I, Saito S, Shiota K, Miyake A, Oka Y, Nakayama R: Kinetic study on disappearance of gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide (DN-1417) from plasma using a radioimmunoassay for DN-1417 isobutylamide. J Pharmacobiodyn. 1983 Mar;6(3):202-8. [6410041 ]
  12. Yeatman DT, Reid K: A study of urinary endogenous gamma-hydroxybutyrate (GHB) levels. J Anal Toxicol. 2003 Jan-Feb;27(1):40-2. [12587682 ]
  13. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  14. Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J (1997). Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins.
  15. NIOSH (1990). NOES: National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication.
  16. BG Chemie (2000). Toxicological Evaluation No. 7: gamma-Butyrolactone (96-48-0).
  17. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  18. Wikipedia. Gamma-Butyrolactone. Last Updated 1 August 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates the circadian expression of clock genes such as CRY1, ARNTL/BMAL1 and NR1D1 in peripheral tissues and in a tissue-selective manner. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORC-mediated activation of the expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Involved in the regulation of the rhythmic expression of genes involved in glucose and lipid metabolism, including PLIN2 and AVPR1A. Negative regulator of adipocyte differentiation through the regulation of early phase genes expression, such as MMP3. Controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. In liver, has specific and redundant functions with RORA as positive or negative modulator of expression of genes encoding phase I and Phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. Also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC and PCK1. Regulates the rhythmic expression of PROX1 and promotes its nuclear localization (By similarity). Plays an indispensable role in the induction of IFN-gamma dependent anti-mycobacterial systemic immunity (PubMed:26160376).Isoform 2: Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes and Peyer's patches. Required for the generation of LTi (lymphoid tissue inducer) cells. Regulates thymocyte survival through DNA-binding on ROREs of target gene promoter regions and recruitment of coactivaros via the AF-2. Also plays a key role, downstream of IL6 and TGFB and synergistically with RORA, for lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. May also play a role in the pre-TCR activation cascade leading to the maturation of alpha/beta T-cells and may participate in the regulation of DNA accessibility in the TCR-J(alpha) locus.
Gene Name:
RORC
Uniprot ID:
P51449
Molecular Weight:
58194.845 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.96 uMATG_RORg_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]