Showing metabocard for D-Limonene (MMDBc0048215)

Record Information
Version1.0
StatusDetected and Quantified
Creation Date2022-04-29 21:53:57 UTC
Update Date2024-04-30 20:35:55 UTC
Metabolite IDMMDBc0048215
Metabolite Identification
Common NameD-Limonene
Description(+)-Limonene, also known as d-limonene, is a naturally occurring monoterpene which is the major component in orange oil. Currently, (+)-limonene is widely used as a flavour 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, (+)-limonene has been shown to cause a male rat-specific kidney toxicity referred to as hyaline droplet nephropathy. Furthermore, chronic exposure to (+)-limonene causes a significant incidence of renal tubular tumours exclusively in male rats. Although (+)-limonene is not carcinogenic in female rats or male and female mice given much higher dosages, the male rat-specific nephrocarcinogenicity of (+)-limonene may raise some concern regarding the safety of (+)-limonene for human consumption. A considerable body of scientific data has indicated that the renal toxicity of (+)-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 (+)-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 (+)-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 (+)-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 demonstrates that the tumorigenic activity of (+)-limonene in male rats is not relevant to humans. The three major lines of evidence supporting the human safety of (+)-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 (+)-limonene and d-limonene-1,2-oxide, supporting the concept of a nongenotoxic mechanism, namely, sustained renal cell proliferation (PMID:2024047 ).
Structure
MOL3D MOLSDF3D SDFPDB3D PDBSMILESInChI

MOL for #<Metabolite:0x0000564af3bb1978>


  Mrv1652303202019022D          

 10 10  0  0  0  0            999 V2000
    0.5360    1.1152    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5360    1.9402    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2505    0.7027    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3218   -0.5346    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8928    1.1152    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6073    0.7027    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6073   -0.1223    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8928   -0.5346    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1782   -0.1223    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1782    0.7027    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
  1  2  2  0  0  0  0
  1  3  1  0  0  0  0
  5  6  1  0  0  0  0
  5 10  1  0  0  0  0
  6  7  1  0  0  0  0
  7  8  2  0  0  0  0
  8  9  1  0  0  0  0
  9 10  1  0  0  0  0
  7  4  1  0  0  0  0
 10  1  1  6  0  0  0
M  END
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3D MOL for #<Metabolite:0x0000564af3bb1978>

HMDB0004321
     RDKit          3D
(-)-Limonene
 26 26  0  0  0  0  0  0  0  0999 V2000
   -2.5269    0.8014   -0.9069 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0720   -0.1283   -0.0819 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9557   -1.2827    0.2816 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7132   -0.0070    0.4560 C   0  0  2  0  0  0  0  0  0  0  0  0
   -0.1242    1.3143    0.0255 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2339    1.4227    0.6369 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0540    0.3995    0.3939 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4314    0.3822    0.9426 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5223   -0.7093   -0.4469 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1928   -1.1652    0.1024 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5387    0.7189   -1.3137 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9633    1.6568   -1.2169 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0018   -1.0559    0.0384 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8545   -1.4287    1.3708 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6763   -2.1915   -0.2970 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7903    0.0391    1.5673 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7756    2.1303    0.3710 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.0311    1.3100   -1.0869 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5806    2.2312    1.2321 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.5665   -0.5545    1.5556 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.1712    0.4284    0.1281 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.5667    1.2659    1.5951 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.2042   -1.5642   -0.4337 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.3539   -0.3681   -1.4946 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2946   -1.8438   -0.6545 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3785   -1.8012    0.9924 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  3
  2  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  7  9  1  0
  9 10  1  0
 10  4  1  0
  1 11  1  0
  1 12  1  0
  3 13  1  0
  3 14  1  0
  3 15  1  0
  4 16  1  1
  5 17  1  0
  5 18  1  0
  6 19  1  0
  8 20  1  0
  8 21  1  0
  8 22  1  0
  9 23  1  0
  9 24  1  0
 10 25  1  0
 10 26  1  0
M  END
Download

3D SDF for #<Metabolite:0x0000564af3bb1978>


  Mrv1652303202019022D          

 10 10  0  0  0  0            999 V2000
    0.5360    1.1152    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5360    1.9402    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2505    0.7027    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3218   -0.5346    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8928    1.1152    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6073    0.7027    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6073   -0.1223    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8928   -0.5346    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1782   -0.1223    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1782    0.7027    0.0000 C   0  0  1  0  0  0  0  0  0  0  0  0
  1  2  2  0  0  0  0
  1  3  1  0  0  0  0
  5  6  1  0  0  0  0
  5 10  1  0  0  0  0
  6  7  1  0  0  0  0
  7  8  2  0  0  0  0
  8  9  1  0  0  0  0
  9 10  1  0  0  0  0
  7  4  1  0  0  0  0
 10  1  1  6  0  0  0
M  END
> <DATABASE_ID>
MMDBc0048215

> <DATABASE_NAME>
MIME

> <SMILES>
CC(=C)[C@H]1CCC(C)=CC1

> <INCHI_IDENTIFIER>
InChI=1S/C10H16/c1-8(2)10-6-4-9(3)5-7-10/h4,10H,1,5-7H2,2-3H3/t10-/m1/s1

> <INCHI_KEY>
XMGQYMWWDOXHJM-SNVBAGLBSA-N

> <FORMULA>
C10H16

> <MOLECULAR_WEIGHT>
136.234

> <EXACT_MASS>
136.125200512

> <JCHEM_ACCEPTOR_COUNT>
0

> <JCHEM_ATOM_COUNT>
26

> <JCHEM_AVERAGE_POLARIZABILITY>
17.226676344955674

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
0

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
0

> <JCHEM_IUPAC>
(4S)-1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene

> <ALOGPS_LOGP>
4.50

> <JCHEM_LOGP>
3.2198126516666665

> <ALOGPS_LOGS>
-2.47

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
1

> <JCHEM_PHYSIOLOGICAL_CHARGE>
0

> <JCHEM_POLAR_SURFACE_AREA>
0.0

> <JCHEM_REFRACTIVITY>
46.4803

> <JCHEM_ROTATABLE_BOND_COUNT>
1

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
4.57e-01 g/l

> <JCHEM_TRADITIONAL_IUPAC>
(-)-limonene

> <JCHEM_VEBER_RULE>
1

$$$$
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3D-SDF for #<Metabolite:0x0000564af3bb1978>

HMDB0004321
     RDKit          3D
(-)-Limonene
 26 26  0  0  0  0  0  0  0  0999 V2000
   -2.5269    0.8014   -0.9069 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0720   -0.1283   -0.0819 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9557   -1.2827    0.2816 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7132   -0.0070    0.4560 C   0  0  2  0  0  0  0  0  0  0  0  0
   -0.1242    1.3143    0.0255 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2339    1.4227    0.6369 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0540    0.3995    0.3939 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4314    0.3822    0.9426 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5223   -0.7093   -0.4469 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1928   -1.1652    0.1024 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5387    0.7189   -1.3137 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9633    1.6568   -1.2169 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0018   -1.0559    0.0384 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8545   -1.4287    1.3708 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6763   -2.1915   -0.2970 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7903    0.0391    1.5673 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7756    2.1303    0.3710 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.0311    1.3100   -1.0869 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.5806    2.2312    1.2321 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.5665   -0.5545    1.5556 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.1712    0.4284    0.1281 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.5667    1.2659    1.5951 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.2042   -1.5642   -0.4337 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.3539   -0.3681   -1.4946 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2946   -1.8438   -0.6545 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.3785   -1.8012    0.9924 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  3
  2  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  1  0
  6  7  2  0
  7  8  1  0
  7  9  1  0
  9 10  1  0
 10  4  1  0
  1 11  1  0
  1 12  1  0
  3 13  1  0
  3 14  1  0
  3 15  1  0
  4 16  1  1
  5 17  1  0
  5 18  1  0
  6 19  1  0
  8 20  1  0
  8 21  1  0
  8 22  1  0
  9 23  1  0
  9 24  1  0
 10 25  1  0
 10 26  1  0
M  END
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PDB for #<Metabolite:0x0000564af3bb1978>

HEADER    PROTEIN                                 20-MAR-20   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   20-MAR-20         0                                  
HETATM    1  C   UNK     0       1.001   2.082   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0       1.001   3.622   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0       2.334   1.312   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0      -4.334  -0.998   0.000  0.00  0.00           C+0
HETATM    5  C   UNK     0      -1.667   2.082   0.000  0.00  0.00           C+0
HETATM    6  C   UNK     0      -3.000   1.312   0.000  0.00  0.00           C+0
HETATM    7  C   UNK     0      -3.000  -0.228   0.000  0.00  0.00           C+0
HETATM    8  C   UNK     0      -1.667  -0.998   0.000  0.00  0.00           C+0
HETATM    9  C   UNK     0      -0.333  -0.228   0.000  0.00  0.00           C+0
HETATM   10  C   UNK     0      -0.333   1.312   0.000  0.00  0.00           C+0
CONECT    1    2    3   10                                                  
CONECT    2    1                                                            
CONECT    3    1                                                            
CONECT    4    7                                                            
CONECT    5    6   10                                                       
CONECT    6    5    7                                                       
CONECT    7    6    8    4                                                  
CONECT    8    7    9                                                       
CONECT    9    8   10                                                       
CONECT   10    5    9    1                                                  
MASTER        0    0    0    0    0    0    0    0   10    0   20    0
END
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3D PDB for #<Metabolite:0x0000564af3bb1978>

COMPND    HMDB0004321
HETATM    1  C1  UNL     1      -2.527   0.801  -0.907  1.00  0.00           C  
HETATM    2  C2  UNL     1      -2.072  -0.128  -0.082  1.00  0.00           C  
HETATM    3  C3  UNL     1      -2.956  -1.283   0.282  1.00  0.00           C  
HETATM    4  C4  UNL     1      -0.713  -0.007   0.456  1.00  0.00           C  
HETATM    5  C5  UNL     1      -0.124   1.314   0.025  1.00  0.00           C  
HETATM    6  C6  UNL     1       1.234   1.423   0.637  1.00  0.00           C  
HETATM    7  C7  UNL     1       2.054   0.399   0.394  1.00  0.00           C  
HETATM    8  C8  UNL     1       3.431   0.382   0.943  1.00  0.00           C  
HETATM    9  C9  UNL     1       1.522  -0.709  -0.447  1.00  0.00           C  
HETATM   10  C10 UNL     1       0.193  -1.165   0.102  1.00  0.00           C  
HETATM   11  H1  UNL     1      -3.539   0.719  -1.314  1.00  0.00           H  
HETATM   12  H2  UNL     1      -1.963   1.657  -1.217  1.00  0.00           H  
HETATM   13  H3  UNL     1      -4.002  -1.056   0.038  1.00  0.00           H  
HETATM   14  H4  UNL     1      -2.854  -1.429   1.371  1.00  0.00           H  
HETATM   15  H5  UNL     1      -2.676  -2.191  -0.297  1.00  0.00           H  
HETATM   16  H6  UNL     1      -0.790   0.039   1.567  1.00  0.00           H  
HETATM   17  H7  UNL     1      -0.776   2.130   0.371  1.00  0.00           H  
HETATM   18  H8  UNL     1       0.031   1.310  -1.087  1.00  0.00           H  
HETATM   19  H9  UNL     1       1.581   2.231   1.232  1.00  0.00           H  
HETATM   20  H10 UNL     1       3.566  -0.555   1.556  1.00  0.00           H  
HETATM   21  H11 UNL     1       4.171   0.428   0.128  1.00  0.00           H  
HETATM   22  H12 UNL     1       3.567   1.266   1.595  1.00  0.00           H  
HETATM   23  H13 UNL     1       2.204  -1.564  -0.434  1.00  0.00           H  
HETATM   24  H14 UNL     1       1.354  -0.368  -1.495  1.00  0.00           H  
HETATM   25  H15 UNL     1      -0.295  -1.844  -0.655  1.00  0.00           H  
HETATM   26  H16 UNL     1       0.378  -1.801   0.992  1.00  0.00           H  
CONECT    1    2    2   11   12
CONECT    2    3    4
CONECT    3   13   14   15
CONECT    4    5   10   16
CONECT    5    6   17   18
CONECT    6    7    7   19
CONECT    7    8    9
CONECT    8   20   21   22
CONECT    9   10   23   24
CONECT   10   25   26
END
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SMILES for #<Metabolite:0x0000564af3bb1978>

CC(=C)[C@H]1CCC(C)=CC1
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INCHI for #<Metabolite:0x0000564af3bb1978>

InChI=1S/C10H16/c1-8(2)10-6-4-9(3)5-7-10/h4,10H,1,5-7H2,2-3H3/t10-/m1/s1
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Synonyms
ValueSource
(-)-(S)-LimoneneChEBI
(-)-(4S)-LimoneneChEBI
(4S)-1-Methyl-4-isopropenylcyclohex-1-eneChEBI
(4S)-4-Isopropenyl-1-methylcyclohexeneChEBI
(S)-(-)-p-Mentha-1,8-dieneChEBI
(S)-1-Methyl-4-(1-methylethenyl)cyclohexeneChEBI
(S)-p-Mentha-1,8-dieneChEBI
4AlphaH-p-mentha-1,8-dieneChEBI
L-LimonenChEBI
L-LimoneneChEBI
4-Isopropenyl-1-methyl-1-cyclohexeneHMDB
LimoneneHMDB
(+)-LimoneneHMDB
AISA 5203-L (+)limoneneHMDB
DipenteneHMDB
1-Methyl-4-(1-methylethenyl)cyclohexeneHMDB
Limonene, (+-)-isomerHMDB
(D)-LimoneneHMDB
4-Mentha-1,8-dieneHMDB
Limonene, (S)-isomerHMDB
Limonene, (R)-isomerHMDB
(R)-(+)-LimoneneHMDB
(R)-4-Isopropenyl-1-methylcyclohexeneHMDB
(+)-(R)-4-Isopropenyl-1-methylcyclohexeneHMDB
(4R)-1-Methyl-4-(1-methylethenyl)cyclohexeneHMDB
D-LimoneneHMDB
4 Mentha 1,8 dieneHMDB
D LimoneneHMDB
(-)-alpha-LimoneneHMDB
(-)-Α-limoneneHMDB
(4S)-1-Methyl-4-(1-methylethenyl)cyclohexeneHMDB
(4S)-LimoneneHMDB
(S)-(-)-LimoneneHMDB
(S)-1-Methyl-4-(prop-1-en-2-yl)cyclohex-1-eneHMDB
(S)-4-Isopropenyl-1-methyl-1-cyclohexeneHMDB
(S)-LimoneneHMDB
beta-LimoneneHMDB
L-CarveneHMDB
Β-limoneneHMDB
(-)-LimoneneChEBI
Molecular FormulaC10H16
Average Mass136.234
Monoisotopic Mass136.125200512
IUPAC Name(4S)-1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene
Traditional Name(-)-limonene
CAS Registry Number5989-54-8
SMILES
CC(=C)[C@H]1CCC(C)=CC1
InChI Identifier
InChI=1S/C10H16/c1-8(2)10-6-4-9(3)5-7-10/h4,10H,1,5-7H2,2-3H3/t10-/m1/s1
InChI KeyXMGQYMWWDOXHJM-SNVBAGLBSA-N