Showing metabocard for 3-Hydroxymethylglutaric acid (MMDBc0000513)

Record Information
Version1.0
StatusDetected and Quantified
Creation Date2020-12-10 18:39:28 UTC
Update Date2024-10-15 18:06:43 UTC
Metabolite IDMMDBc0000513
Metabolite Identification
Common Name3-Hydroxymethylglutaric acid
Description3-Hydroxymethylglutaric acid is an "off-product" intermediate in the leucine degradation process. It is produced by defective or inefficient versions of 3-hydroxy-3-methylglutaryl-CoA lyase, an enzyme that normally catalyzes the conversion of 3-hydroxy-3-methylglutaryl-CoA to acetyl-CoA and acetoacetate. If this enzyme is defective, 3-hydroxy-3-methylglutaryl-CoA will accumulate in the mitochondria. Increased concentrations of 3-hydroxy-3-methylglutaryl-CoA can lead to a disruption of the esterified CoA:free CoA ratio and ultimately to mitochondrial toxicity. Detoxification of these CoA end products occurs via the transfer of the 3-hydroxymethylglutaryl moiety to carnitine, forming 3-hydroxymethylglutaric-carnitine, which is then transferred across the inner mitochondrial membrane where 3-hydroxymethylglutaric acid is released as the free acid. 3-Hydroxymethylglutaric acid has been found to accumulate in the urine of patients affected by 3-Hydroxy-3-methylglutaric aciduria, a rare inborn error of metabolism (OMIM: 246450 ). 3-Hydroxy-3-methylglutaric aciduria is caused by significantly reduced enzyme activity of the intramitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase (EC 4.1.3.4), the enzyme that catalyzes the final step of leucine degradation. This enzyme also plays a key role in ketone body formation. The profile of urinary organic acids for individuals with 3-hydroxy-3-methylglutaric aciduria is different from that of the other identified defects of leucine degradation, such as maple syrup urine disease (OMIM: 248600 ), isovaleric acidemia (OMIM: 243500 ), and methylcrotonylglycinemia (OMIM: 210200 ). The urinary organic acid profile of 3-hydroxy-3-methylglutaric aciduria includes elevated concentrations of 3-hydroxy-3-isovaleric, 3-hydroxy-3-methylglutaric, 3-methylglutaconic, and 3-methylglutaric acids (PMID: 10916782 , 9658458 , 3063529 ). Clinical manifestations of 3-hydroxy-3-methylglutaric aciduria include hepatomegaly, lethargy, coma, and apnea. Biochemically, there is a characteristic absence of ketosis with hypoglycemia, acidosis, hypertransaminasemia, and variable hyperammonemia. Therefore, when present in sufficiently high concentrations, 3-hydroxymethylglutaric acid can act as an acidogen and a metabotoxin. An acidogen is an acidic compound that induces acidosis, which has multiple adverse effects on many organ systems. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. As noted above, chronically high levels of 3-hydroxymethylglutaric acid are associated with the inborn error of metabolism 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. 3-Hydroxymethylglutaric acid is an organic acid. Abnormally high levels of organic acids in the blood (organic acidemia), urine (organic aciduria), the brain, and other tissues lead to general metabolic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy). These can progress to heart, liver, and kidney abnormalities, seizures, coma, and possibly death. These are also the characteristic symptoms of the untreated IEMs mentioned above. Many affected children with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures.
Structure
MOL3D MOLSDF3D SDFPDB3D PDBSMILESInChI

MOL for #<Metabolite:0x00007f91d161ecb0>


  Mrv1652305261923572D          

 11 10  0  0  0  0            999 V2000
 9999.2905 9997.9678    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9998.5756 9998.3795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9997.8608 9997.9678    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9997.1459 9998.3795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9996.4310 9997.9678    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9997.1459 9999.2054    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9998.9892 9999.0960    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9998.1638 9999.0960    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
10000.0084 9998.3795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10000.7223 9997.9678    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
10000.0084 9999.2054    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  1  9  1  0  0  0  0
  2  3  1  0  0  0  0
  2  7  1  0  0  0  0
  2  8  1  0  0  0  0
  3  4  1  0  0  0  0
  4  5  1  0  0  0  0
  4  6  2  0  0  0  0
  9 10  1  0  0  0  0
  9 11  2  0  0  0  0
M  END
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3D MOL for #<Metabolite:0x00007f91d161ecb0>

HMDB0000355
     RDKit          3D
3-Hydroxymethylglutaric acid
 21 20  0  0  0  0  0  0  0  0999 V2000
   -0.2537    1.0361   -1.5362 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0018   -0.1340   -0.6708 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1538   -1.1921   -1.7139 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.3140   -0.2263    0.0025 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7498    0.8221    0.8872 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1617    1.8929    1.0942 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.9446    0.6400    1.5902 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1052   -0.6915    0.1211 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8242    0.1036    1.0798 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7311    1.3111    1.3537 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8015   -0.5708    1.8495 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5155    1.9691   -1.0058 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.6801    1.2509   -2.1043 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0179    0.7906   -2.3122 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6842   -1.1227   -2.2457 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.3737   -1.1993    0.5951 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.1661   -0.3866   -0.7434 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.6328   -0.0496    1.3287 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9155   -1.1549   -0.5437 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7466   -1.6272    0.6706 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5830   -1.4614    2.3031 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  2  0
  5  7  1  0
  2  8  1  0
  8  9  1  0
  9 10  2  0
  9 11  1  0
  1 12  1  0
  1 13  1  0
  1 14  1  0
  3 15  1  0
  4 16  1  0
  4 17  1  0
  7 18  1  0
  8 19  1  0
  8 20  1  0
 11 21  1  0
M  END
Download

3D SDF for #<Metabolite:0x00007f91d161ecb0>


  Mrv1652305261923572D          

 11 10  0  0  0  0            999 V2000
 9999.2905 9997.9678    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9998.5756 9998.3795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9997.8608 9997.9678    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9997.1459 9998.3795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9996.4310 9997.9678    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9997.1459 9999.2054    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9998.9892 9999.0960    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9998.1638 9999.0960    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
10000.0084 9998.3795    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10000.7223 9997.9678    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
10000.0084 9999.2054    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  1  9  1  0  0  0  0
  2  3  1  0  0  0  0
  2  7  1  0  0  0  0
  2  8  1  0  0  0  0
  3  4  1  0  0  0  0
  4  5  1  0  0  0  0
  4  6  2  0  0  0  0
  9 10  1  0  0  0  0
  9 11  2  0  0  0  0
M  END
> <DATABASE_ID>
MMDBc0000513

> <DATABASE_NAME>
MIME

> <SMILES>
CC(O)(CC(O)=O)CC(O)=O

> <INCHI_IDENTIFIER>
InChI=1S/C6H10O5/c1-6(11,2-4(7)8)3-5(9)10/h11H,2-3H2,1H3,(H,7,8)(H,9,10)

> <INCHI_KEY>
NPOAOTPXWNWTSH-UHFFFAOYSA-N

> <FORMULA>
C6H10O5

> <MOLECULAR_WEIGHT>
162.1406

> <EXACT_MASS>
162.05282343

> <JCHEM_ACCEPTOR_COUNT>
5

> <JCHEM_ATOM_COUNT>
21

> <JCHEM_AVERAGE_POLARIZABILITY>
14.545141112043254

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
3

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
0

> <JCHEM_IUPAC>
3-hydroxy-3-methylpentanedioic acid

> <ALOGPS_LOGP>
-0.88

> <JCHEM_LOGP>
-0.7482412409999999

> <ALOGPS_LOGS>
0.23

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
0

> <JCHEM_PHYSIOLOGICAL_CHARGE>
-2

> <JCHEM_PKA>
4.435120601836896

> <JCHEM_PKA_STRONGEST_ACIDIC>
3.6777896096277964

> <JCHEM_PKA_STRONGEST_BASIC>
-3.0082279564358467

> <JCHEM_POLAR_SURFACE_AREA>
94.83000000000001

> <JCHEM_REFRACTIVITY>
34.1377

> <JCHEM_ROTATABLE_BOND_COUNT>
4

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
2.75e+02 g/l

> <JCHEM_TRADITIONAL_IUPAC>
meglutol

> <JCHEM_VEBER_RULE>
0

$$$$
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3D-SDF for #<Metabolite:0x00007f91d161ecb0>

HMDB0000355
     RDKit          3D
3-Hydroxymethylglutaric acid
 21 20  0  0  0  0  0  0  0  0999 V2000
   -0.2537    1.0361   -1.5362 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0018   -0.1340   -0.6708 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1538   -1.1921   -1.7139 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.3140   -0.2263    0.0025 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7498    0.8221    0.8872 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1617    1.8929    1.0942 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.9446    0.6400    1.5902 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1052   -0.6915    0.1211 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8242    0.1036    1.0798 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7311    1.3111    1.3537 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8015   -0.5708    1.8495 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5155    1.9691   -1.0058 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.6801    1.2509   -2.1043 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0179    0.7906   -2.3122 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6842   -1.1227   -2.2457 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.3737   -1.1993    0.5951 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.1661   -0.3866   -0.7434 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.6328   -0.0496    1.3287 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9155   -1.1549   -0.5437 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7466   -1.6272    0.6706 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5830   -1.4614    2.3031 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  2  0
  5  7  1  0
  2  8  1  0
  8  9  1  0
  9 10  2  0
  9 11  1  0
  1 12  1  0
  1 13  1  0
  1 14  1  0
  3 15  1  0
  4 16  1  0
  4 17  1  0
  7 18  1  0
  8 19  1  0
  8 20  1  0
 11 21  1  0
M  END
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PDB for #<Metabolite:0x00007f91d161ecb0>

HEADER    PROTEIN                                 26-MAY-19   NONE
TITLE     NULL                                                        
COMPND    NULL                                                        
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   26-MAY-19         0                                  
HETATM    1  C   UNK     0    8665.3428662.873   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0    8664.0088663.642   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0    8662.6748662.873   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0    8661.3398663.642   0.000  0.00  0.00           C+0
HETATM    5  O   UNK     0    8660.0058662.873   0.000  0.00  0.00           O+0
HETATM    6  O   UNK     0    8661.3398665.183   0.000  0.00  0.00           O+0
HETATM    7  C   UNK     0    8664.7808664.979   0.000  0.00  0.00           C+0
HETATM    8  O   UNK     0    8663.2398664.979   0.000  0.00  0.00           O+0
HETATM    9  C   UNK     0    8666.6828663.642   0.000  0.00  0.00           C+0
HETATM   10  O   UNK     0    8668.0158662.873   0.000  0.00  0.00           O+0
HETATM   11  O   UNK     0    8666.6828665.183   0.000  0.00  0.00           O+0
CONECT    1    2    9                                                       
CONECT    2    1    3    7    8                                             
CONECT    3    2    4                                                       
CONECT    4    3    5    6                                                  
CONECT    5    4                                                            
CONECT    6    4                                                            
CONECT    7    2                                                            
CONECT    8    2                                                            
CONECT    9    1   10   11                                                  
CONECT   10    9                                                            
CONECT   11    9                                                            
MASTER        0    0    0    0    0    0    0    0   11    0   20    0
END
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3D PDB for #<Metabolite:0x00007f91d161ecb0>

COMPND    HMDB0000355
HETATM    1  C1  UNL     1      -0.254   1.036  -1.536  1.00  0.00           C  
HETATM    2  C2  UNL     1       0.002  -0.134  -0.671  1.00  0.00           C  
HETATM    3  O1  UNL     1       0.154  -1.192  -1.714  1.00  0.00           O  
HETATM    4  C3  UNL     1       1.314  -0.226   0.003  1.00  0.00           C  
HETATM    5  C4  UNL     1       1.750   0.822   0.887  1.00  0.00           C  
HETATM    6  O2  UNL     1       1.162   1.893   1.094  1.00  0.00           O  
HETATM    7  O3  UNL     1       2.945   0.640   1.590  1.00  0.00           O  
HETATM    8  C5  UNL     1      -1.105  -0.691   0.121  1.00  0.00           C  
HETATM    9  C6  UNL     1      -1.824   0.104   1.080  1.00  0.00           C  
HETATM   10  O4  UNL     1      -1.731   1.311   1.354  1.00  0.00           O  
HETATM   11  O5  UNL     1      -2.801  -0.571   1.849  1.00  0.00           O  
HETATM   12  H1  UNL     1      -0.515   1.969  -1.006  1.00  0.00           H  
HETATM   13  H2  UNL     1       0.680   1.251  -2.104  1.00  0.00           H  
HETATM   14  H3  UNL     1      -1.018   0.791  -2.312  1.00  0.00           H  
HETATM   15  H4  UNL     1      -0.684  -1.123  -2.246  1.00  0.00           H  
HETATM   16  H5  UNL     1       1.374  -1.199   0.595  1.00  0.00           H  
HETATM   17  H6  UNL     1       2.166  -0.387  -0.743  1.00  0.00           H  
HETATM   18  H7  UNL     1       3.633  -0.050   1.329  1.00  0.00           H  
HETATM   19  H8  UNL     1      -1.915  -1.155  -0.544  1.00  0.00           H  
HETATM   20  H9  UNL     1      -0.747  -1.627   0.671  1.00  0.00           H  
HETATM   21  H10 UNL     1      -2.583  -1.461   2.303  1.00  0.00           H  
CONECT    1    2   12   13   14
CONECT    2    3    4    8
CONECT    3   15
CONECT    4    5   16   17
CONECT    5    6    6    7
CONECT    7   18
CONECT    8    9   19   20
CONECT    9   10   10   11
CONECT   11   21
END
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SMILES for #<Metabolite:0x00007f91d161ecb0>

CC(O)(CC(O)=O)CC(O)=O
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INCHI for #<Metabolite:0x00007f91d161ecb0>

InChI=1S/C6H10O5/c1-6(11,2-4(7)8)3-5(9)10/h11H,2-3H2,1H3,(H,7,8)(H,9,10)
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Synonyms
ValueSource
(S)-3-Hydroxy-3-methylglutaric acidChEBI
(S)-MeglutolChEBI
3-HYDROXY-3-methyl-glutarIC ACIDChEBI
3-Hydroxy-3-methylpentanedioic acidChEBI
beta-Hydroxy-beta-methylglutaric acidChEBI
Dicrotalic acidChEBI
MeglutolChEBI
MeglutolumChEBI
3-Hydorxy-3-methylglutaric acidKegg
(S)-3-Hydroxy-3-methylglutarateGenerator
3-HYDROXY-3-methyl-glutarateGenerator
3-Hydroxy-3-methylpentanedioateGenerator
b-Hydroxy-b-methylglutarateGenerator
b-Hydroxy-b-methylglutaric acidGenerator
beta-Hydroxy-beta-methylglutarateGenerator
Β-hydroxy-β-methylglutarateGenerator
Β-hydroxy-β-methylglutaric acidGenerator
DicrotalateGenerator
3-Hydorxy-3-methylglutarateGenerator
3-HydroxymethylglutarateGenerator
3-Hydroxy-3-methylglutarateHMDB
3-Hydroxy-3-methylglutaric acidHMDB
3-Methyl-3-hydroxyglutarateHMDB
3-Methyl-3-hydroxyglutaric acidHMDB
CB 337HMDB
3 Hydroxy 3 methylpentanedioic acidHMDB
Acid, 3-hydroxy-3-methylglutaricHMDB
Acid, 3-hydroxy-3-methylpentanedioicHMDB
beta Hydroxy beta methylglutarateHMDB
3 Hydroxy 3 methylglutaric acidHMDB
3-Methyl-3-hydroxypentanedioateHMDB
3-Methyl-3-hydroxypentanedioic acidHMDB
HMGHMDB
HMGAHMDB
LipoglutarenHMDB
MedroglutarateHMDB
Medroglutaric acidHMDB
Molecular FormulaC6H10O5
Average Mass162.1406
Monoisotopic Mass162.05282343
IUPAC Name3-hydroxy-3-methylpentanedioic acid
Traditional Namemeglutol
CAS Registry NumberNot Available
SMILES
CC(O)(CC(O)=O)CC(O)=O
InChI Identifier
InChI=1S/C6H10O5/c1-6(11,2-4(7)8)3-5(9)10/h11H,2-3H2,1H3,(H,7,8)(H,9,10)
InChI KeyNPOAOTPXWNWTSH-UHFFFAOYSA-N