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Bovine Metabolome Database



Showing metabocard for (-)-Limonene (BMDB03375)

Legend: metabolite field enzyme field

Version 1.0
Creation Date 2006-08-12 20:51:01
Update Date 2009-05-05 20:59:36
Accession Number BMDB03375
Common Name (-)-Limonene
Description The monoterpene d-limonene is a naturally occurring chemical which is the major component in oil of orange. Currently, d-limonene is widely used as a flavor and fragrance and is listed to be generally recognized as safe in food by the Food and Drug Administration (21 CFR 182.60 in the Code of Federal Regulations, U.S.A.). Recently, however, d-limonene has been shown to cause a male rat-specific kidney toxicity referred to as hyaline droplet nephropathy. Furthermore, chronic exposure to d-limonene causes a significant incidence of renal tubular tumors exclusively in male rats. Although d-limonene is not carcinogenic in female rats or male and female mice given much higher dosages, the male rat-specific nephrocarcinogenicity of d-limonene may raise some concern regarding the safety of d-limonene for human consumption. A considerable body of scientific data has indicated that the renal toxicity of d-limonene results from the accumulation of a protein, alpha 2u-globulin, in male rat kidney proximal tubule lysosomes. This protein is synthesized exclusively by adult male rats. Other species, including humans, synthesize proteins that share significant homology with alpha 2u-globulin. However, none of these proteins, including the mouse equivalent of alpha 2u-globulin, can produce this toxicity, indicating a unique specificity for alpha 2u-globulin. With chronic exposure to d-limonene, the hyaline droplet nephropathy progresses and the kidney shows tubular cell necrosis, granular cast formation at the corticomedullary junction, and compensatory cell proliferation. Both d-limonene and cis-d-limonene-1,2-oxide (the major metabolite involved in this toxicity) are negative in vitro mutagenicity screens. Therefore, the toxicity-related renal cell proliferation is believed to be integrally involved in the carcinogenicity of d-limonene as persistent elevations in renal cell proliferation may increase fixation of spontaneously altered DNA or serve to promote spontaneously initiated cells. The scientific data base demonstrates that the tumorigenic activity of d-limonene in male rats is not relevant to humans. The three major lines of evidence supporting the human safety of d-limonene are (1) the male rat specificity of the nephrotoxicity and carcinogenicity; (2) the pivotal role that alpha 2u-globulin plays in the toxicity, as evidenced by the complete lack of toxicity in other species despite the presence of structurally similar proteins; and (3) the lack of genotoxicity of both d-limonene and d-limonene-1,2-oxide, supporting the concept of a nongenotoxic mechanism, namely, sustained renal cell proliferation. (PMID: 2024047)
Synonyms
  1. (-)-(4S)-Limonene
  2. (-)-(S)-Limonene
  3. 4-Isopropenyl-1-methyl-1-cyclohexene
  4. L-Limonene
  5. Limonene
  6. d-Limonene
Chemical IUPAC Name (4S)-1-methyl-4-prop-1-en-2-yl-cyclohexene
Chemical Formula C10H16
Chemical Structure Structure
Chemical Taxonomy
Kingdom
  • Organic
Super Class
  • Miscellanous
Class
  • Alkanes and Alkenes; Monoterpenes
Sub Class
  • Medium chain alkenes
Family
  • Mammalian_Metabolite
Species
  • alkene
Biofunction
  • Component of Monoterpenoid biosynthesis
Application
Source
  • Endogenous
Average Molecular Weight 136.234
Monoisotopic Molecular Weight 136.125198
Isomeric SMILES CC(=C)[C@H]1CCC(C)=CC1
Canonical SMILES CC(=C)C1CCC(C)=CC1
KEGG Compound ID C00521 Link Image
BioCyc ID -R-LIMONENE Link Image
BiGG ID 47361 Link Image
Wikipedia Link Limonene Link Image
METLIN ID 6911 Link Image
PubChem Compound 439250 Link Image
PubChem Substance 3804 Link Image
ChEBI ID 15383 Link Image
CAS Registry Number 5989-54-8
InChI Identifier InChI=1/C10H16/c1-8(2)10-6-4-9(3)5-7-10/h4,10H,1,5-7H2,2-3H3/t10-/m1/s1
Synthesis Reference v. Braun, Julius; Lemke, Georg. Preparation of pure d- and l-limonene. Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen (1923), 56B 1562-3.
Melting Point (Experimental) -90 oC
Experimental Water Solubility Not Available Source: PhysProp
Predicted Water Solubility 0.00315 mg/mL at 25 oC [MEYLAN,WM et al. (1996)]; 0.45700002 mg/mL [Predicted by ALOGPS] Calculated using ALOGPS
Physiological Charge 0
State Liquid
Experimental LogP/Hydrophobicity 4.38 [GRIFFIN,S ET AL. (1999)] Source: PhysProp
Predicted LogP/Hydrophobicity 4.50 [Predicted by ALOGPS]; 3.7 [Predicted by PubChem via XLOGP] Calculated using ALOGPS
Material Safety Data Sheet (MSDS)
MOL File Show
SDF File Show
PDB File Show
2D Structure
3D Structure
Experimental PDB ID Not Available
Experimental 1H NMR Spectrum Download Spectrum
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Experimental 13C NMR Spectrum Not Available
Experimental 13C HSQC Spectrum Download Spectrum
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Predicted 1H NMR Spectrum Show Image
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Predicted 13C NMR Spectrum Show Image
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Mass Spectrum
Low Energy
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Medium Energy
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High Energy
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Simplified TOCSY Spectrum Not Available
BMRB Spectrum Not Available
Cellular Location
  • Membrane (Predicted from LogP)
  • Cytoplasm
  • Extracellular
Biofluid Location Not Available
Tissue Location
Tissue References
Epidermis
Skin
Stratum Corneum
Concentrations (Normal) Not Available
Concentrations (Abnormal) Not Available
Pathway Names Not Available
HMDB Pathways Not Available
KEGG Pathways Not Available
SimCell Pathways Not Available
General References
  1. Wikipedia Link Image