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Showing NP-Card for 3-Hydroxyisovaleric acid (NP0001323)

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Record Information
Version1.0
Created at2005-11-16 15:48:42 UTC
Updated at2021-08-19 23:59:02 UTC
NP-MRD IDNP0001323
Secondary Accession NumbersNone
Natural Product Identification
Common Name3-Hydroxyisovaleric acid
Description3-Hydroxyisovaleric acid is a normal human metabolite excreted in the urine. It is a byproduct of the leucine degradation pathway. Production of 3-hydroxyisovaleric acid begins with the conversion of 3-methylcrotonyl-CoA into 3-methylglutaconyl-CoA in the mitochondria by the biotin-dependent enzyme methylcrotonyl-CoA carboxylase. Biotin deficiencies, certain lifestyle habits (smoking), or specific genetic conditions can reduce methylcrotonyl-CoA carboxylase activity. This reduction can lead to a buildup of 3-methylcrotonyl-CoA, which is converted into 3-hydroxyisovaleryl-CoA by the enzyme enoyl-CoA hydratase. Increased concentrations of 3-methylcrotonyl-CoA and 3-hydroxyisovaleryl-CoA can lead to a disruption of the esterified CoA:Free CoA ratio, and ultimately to mitochondrial toxicity. Detoxification of these metabolic end products occur via the transfer of the 3-hydroxyisovaleryl moiety to carnitine forming 3-hydroxyisovaleric acid-carnitine or 3HIA-carnitine, which is then transferred across the inner mitochondrial membrane where 3-hydroxyisovaleric acid is released as the free acid (PMID: 21918059 ). 3-Hydroxyisovaleric acid has been found to be elevated in smokers and in subjects undergoing long-term anticonvulsant therapy with carbamazepine and/or phenytoin. These levels are elevated due to impairment of renal reclamation of biotin. Levels may also be increased from prolonged consumption of raw egg-whites (PMID: 16895887 , 9523856 , 15447901 , 9176832 ) (OMIM: 210210 , 253270 , 600529 , 253260 , 246450 , 210200 , 238331 ). When present in sufficiently high levels, 3-hydroxyisovaleric 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. Chronically high levels of 3-hydroxyisovaleric acid are associated with at least a dozen inborn errors of metabolism, including 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, 3-methylglutaconic aciduria type I, biotinidase deficiency and isovaleric aciduria, dihydrolipoamide dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase 1 deficiency, 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, late-onset multiple carboxylase deficiency, holocarboxylase synthetase deficiency, and 3-methylcrotonyl-CoA carboxylase 2 deficiency. 3-Hydroxyisovaleric 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
Thumb
MOL3D MOLSDF3D SDFPDB3D PDBSMILESInChI

MOL for NP0001323 (3-Hydroxyisovaleric acid)

      
  Mrv1652305261923572D          

  8  7  0  0  0  0            999 V2000
10000.646310000.0428    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10001.361410000.4542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10002.074610000.0428    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10001.773710001.1700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10000.949110001.1700    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9999.931810000.4542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9999.217510000.0428    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9999.931810001.2792    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  1  6  1  0  0  0  0
  2  3  1  0  0  0  0
  2  4  1  0  0  0  0
  2  5  1  0  0  0  0
  6  7  1  0  0  0  0
  6  8  2  0  0  0  0
M  END
Download

3D MOL for NP0001323 (3-Hydroxyisovaleric acid)

HMDB0000754
     RDKit          3D
3-Hydroxyisovaleric acid
 18 17  0  0  0  0  0  0  0  0999 V2000
   -1.0475   -1.4321   -0.9596 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5313   -0.0583   -0.5105 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3016    0.3065    0.7240 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7312    0.8091   -1.5609 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.9305   -0.2216   -0.2302 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5814    1.0256    0.2175 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9968    2.1281    0.3592 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.9390    0.9803    0.5037 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0666   -1.3298   -1.4167 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0537   -2.1413   -0.0956 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3662   -1.7656   -1.7480 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1744   -0.3798    0.9060 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6369    0.2013    1.6003 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7061    1.3212    0.6762 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9259    1.7312   -1.3024 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.0830   -1.0423    0.5297 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.4323   -0.5231   -1.1849 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.5783    0.3906   -0.0128 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
  2  5  1  0
  5  6  1  0
  6  7  2  0
  6  8  1  0
  1  9  1  0
  1 10  1  0
  1 11  1  0
  3 12  1  0
  3 13  1  0
  3 14  1  0
  4 15  1  0
  5 16  1  0
  5 17  1  0
  8 18  1  0
M  END
Download

3D SDF for NP0001323 (3-Hydroxyisovaleric acid)

      
  Mrv1652305261923572D          

  8  7  0  0  0  0            999 V2000
10000.646310000.0428    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10001.361410000.4542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10002.074610000.0428    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10001.773710001.1700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
10000.949110001.1700    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9999.931810000.4542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 9999.217510000.0428    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
 9999.931810001.2792    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  1  6  1  0  0  0  0
  2  3  1  0  0  0  0
  2  4  1  0  0  0  0
  2  5  1  0  0  0  0
  6  7  1  0  0  0  0
  6  8  2  0  0  0  0
M  END
> <DATABASE_ID>
NP0001323

> <DATABASE_NAME>
NP-MRD

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

> <INCHI_IDENTIFIER>
InChI=1S/C5H10O3/c1-5(2,8)3-4(6)7/h8H,3H2,1-2H3,(H,6,7)

> <INCHI_KEY>
AXFYFNCPONWUHW-UHFFFAOYSA-N

> <FORMULA>
C5H10O3

> <MOLECULAR_WEIGHT>
118.1311

> <EXACT_MASS>
118.062994186

> <JCHEM_ACCEPTOR_COUNT>
3

> <JCHEM_ATOM_COUNT>
18

> <JCHEM_AVERAGE_POLARIZABILITY>
11.74803117886822

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
2

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
0

> <JCHEM_IUPAC>
3-hydroxy-3-methylbutanoic acid

> <ALOGPS_LOGP>
-0.12

> <JCHEM_LOGP>
-0.10642933099999986

> <ALOGPS_LOGS>
0.51

> <JCHEM_MDDR_LIKE_RULE>
0

> <JCHEM_NUMBER_OF_RINGS>
0

> <JCHEM_PHYSIOLOGICAL_CHARGE>
-1

> <JCHEM_PKA>
15.417396678218886

> <JCHEM_PKA_STRONGEST_ACIDIC>
4.554638714853443

> <JCHEM_PKA_STRONGEST_BASIC>
-2.7419355220135504

> <JCHEM_POLAR_SURFACE_AREA>
57.53

> <JCHEM_REFRACTIVITY>
28.1023

> <JCHEM_ROTATABLE_BOND_COUNT>
2

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
3.84e+02 g/l

> <JCHEM_TRADITIONAL_IUPAC>
3-hydroxyisovaleric acid

> <JCHEM_VEBER_RULE>
0

$$$$
Download

3D-SDF for NP0001323 (3-Hydroxyisovaleric acid)

HMDB0000754
     RDKit          3D
3-Hydroxyisovaleric acid
 18 17  0  0  0  0  0  0  0  0999 V2000
   -1.0475   -1.4321   -0.9596 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5313   -0.0583   -0.5105 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3016    0.3065    0.7240 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7312    0.8091   -1.5609 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.9305   -0.2216   -0.2302 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5814    1.0256    0.2175 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9968    2.1281    0.3592 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.9390    0.9803    0.5037 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0666   -1.3298   -1.4167 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0537   -2.1413   -0.0956 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3662   -1.7656   -1.7480 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1744   -0.3798    0.9060 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6369    0.2013    1.6003 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7061    1.3212    0.6762 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9259    1.7312   -1.3024 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.0830   -1.0423    0.5297 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.4323   -0.5231   -1.1849 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.5783    0.3906   -0.0128 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
  2  5  1  0
  5  6  1  0
  6  7  2  0
  6  8  1  0
  1  9  1  0
  1 10  1  0
  1 11  1  0
  3 12  1  0
  3 13  1  0
  3 14  1  0
  4 15  1  0
  5 16  1  0
  5 17  1  0
  8 18  1  0
M  END
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PDB for NP0001323 (3-Hydroxyisovaleric acid)

HEADER    PROTEIN                                 26-MAY-19   NONE
TITLE     NULL                                                        
COMPND    MOLECULE:                                                   
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   26-MAY-19         0                                  
HETATM    1  C   UNK     0    8667.8738666.747   0.000  0.00  0.00           C+0
HETATM    2  C   UNK     0    8669.2088667.515   0.000  0.00  0.00           C+0
HETATM    3  C   UNK     0    8670.5398666.747   0.000  0.00  0.00           C+0
HETATM    4  C   UNK     0    8669.9788668.851   0.000  0.00  0.00           C+0
HETATM    5  O   UNK     0    8668.4388668.851   0.000  0.00  0.00           O+0
HETATM    6  C   UNK     0    8666.5398667.515   0.000  0.00  0.00           C+0
HETATM    7  O   UNK     0    8665.2068666.747   0.000  0.00  0.00           O+0
HETATM    8  O   UNK     0    8666.5398669.055   0.000  0.00  0.00           O+0
CONECT    1    2    6                                                       
CONECT    2    1    3    4    5                                             
CONECT    3    2                                                            
CONECT    4    2                                                            
CONECT    5    2                                                            
CONECT    6    1    7    8                                                  
CONECT    7    6                                                            
CONECT    8    6                                                            
MASTER        0    0    0    0    0    0    0    0    8    0   14    0
END
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3D PDB for NP0001323 (3-Hydroxyisovaleric acid)

COMPND    HMDB0000754
HETATM    1  C1  UNL     1      -1.047  -1.432  -0.960  1.00  0.00           C  
HETATM    2  C2  UNL     1      -0.531  -0.058  -0.511  1.00  0.00           C  
HETATM    3  C3  UNL     1      -1.302   0.307   0.724  1.00  0.00           C  
HETATM    4  O1  UNL     1      -0.731   0.809  -1.561  1.00  0.00           O  
HETATM    5  C4  UNL     1       0.931  -0.222  -0.230  1.00  0.00           C  
HETATM    6  C5  UNL     1       1.581   1.026   0.217  1.00  0.00           C  
HETATM    7  O2  UNL     1       0.997   2.128   0.359  1.00  0.00           O  
HETATM    8  O3  UNL     1       2.939   0.980   0.504  1.00  0.00           O  
HETATM    9  H1  UNL     1      -2.067  -1.330  -1.417  1.00  0.00           H  
HETATM   10  H2  UNL     1      -1.054  -2.141  -0.096  1.00  0.00           H  
HETATM   11  H3  UNL     1      -0.366  -1.766  -1.748  1.00  0.00           H  
HETATM   12  H4  UNL     1      -2.174  -0.380   0.906  1.00  0.00           H  
HETATM   13  H5  UNL     1      -0.637   0.201   1.600  1.00  0.00           H  
HETATM   14  H6  UNL     1      -1.706   1.321   0.676  1.00  0.00           H  
HETATM   15  H7  UNL     1      -0.926   1.731  -1.302  1.00  0.00           H  
HETATM   16  H8  UNL     1       1.083  -1.042   0.530  1.00  0.00           H  
HETATM   17  H9  UNL     1       1.432  -0.523  -1.185  1.00  0.00           H  
HETATM   18  H10 UNL     1       3.578   0.391  -0.013  1.00  0.00           H  
CONECT    1    2    9   10   11
CONECT    2    3    4    5
CONECT    3   12   13   14
CONECT    4   15
CONECT    5    6   16   17
CONECT    6    7    7    8
CONECT    8   18
END
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SMILES for NP0001323 (3-Hydroxyisovaleric acid)

CC(C)(O)CC(O)=O
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INCHI for NP0001323 (3-Hydroxyisovaleric acid)

InChI=1S/C5H10O3/c1-5(2,8)3-4(6)7/h8H,3H2,1-2H3,(H,6,7)
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View in JSmol
Synonyms
ValueSource
3-Hydroxy-3-methylbutyric acidChEBI
3-Hydroxy-isovaleric acidChEBI
3-Methyl-3-hydroxybutyric acidChEBI
3-OH-Isovaleric acidChEBI
beta-Hydroxy-beta-methylbutyric acidChEBI
beta-Hydroxyisovaleric acidChEBI
HMBChEBI
HMB-D6ChEBI
3-Hydroxy-3-methylbutyrateGenerator
3-Hydroxy-isovalerateGenerator
3-Methyl-3-hydroxybutyrateGenerator
3-OH-IsovalerateGenerator
b-Hydroxy-b-methylbutyrateGenerator
b-Hydroxy-b-methylbutyric acidGenerator
beta-Hydroxy-beta-methylbutyrateGenerator
Β-hydroxy-β-methylbutyrateGenerator
Β-hydroxy-β-methylbutyric acidGenerator
b-HydroxyisovalerateGenerator
b-Hydroxyisovaleric acidGenerator
beta-HydroxyisovalerateGenerator
Β-hydroxyisovalerateGenerator
Β-hydroxyisovaleric acidGenerator
3-HydroxyisovalerateGenerator
beta Hydroxy beta methylbutyrateHMDB
beta-Hydroxy beta-methylbutyrateHMDB
3-Hydroxy-3-methyl-butanoateHMDB
3-Hydroxy-3-methyl-butanoic acidHMDB
3-Hydroxy-3-methyl-butyric acidHMDB
3-Hydroxy-3-methylbutanoateHMDB
3-Hydroxy-3-methylbutanoic acidHMDB
3-Hydroxyisovaleric acidMeSH
Chemical FormulaC5H10O3
Average Mass118.1311 Da
Monoisotopic Mass118.06299 Da
IUPAC Name3-hydroxy-3-methylbutanoic acid
Traditional Name3-hydroxyisovaleric acid
CAS Registry Number625-08-1
SMILES
CC(C)(O)CC(O)=O
InChI Identifier
InChI=1S/C5H10O3/c1-5(2,8)3-4(6)7/h8H,3H2,1-2H3,(H,6,7)
InChI KeyAXFYFNCPONWUHW-UHFFFAOYSA-N
Experimental Spectra
Spectrum TypeDescriptionDepositor EmailDepositor OrganizationDepositorDeposition DateView
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, simulated)Varshavi.d262021-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Varshavi.d262021-08-20View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
Predicted Spectra
Not Available
Chemical Shift Submissions
Spectrum TypeDescriptionDepositor IDDepositor OrganizationDepositorDeposition DateView
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, simulated)Varshavi.d262021-08-17View Spectrum
Species
Species of Origin
Species NameSourceReference
Aloe africanaLOTUS Database
Apis ceranaLOTUS Database
Arabidopsis thalianaLOTUS Database
Chemical Taxonomy
Description Belongs to the class of organic compounds known as hydroxy fatty acids. These are fatty acids in which the chain bears a hydroxyl group.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentHydroxy fatty acids
Alternative Parents
Substituents
  • Methyl-branched fatty acid
  • Short-chain hydroxy acid
  • Hydroxy fatty acid
  • Branched fatty acid
  • Tertiary alcohol
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point65 - 67 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP6.300The Good Scents Company Information System
Predicted Properties
PropertyValueSource
Water Solubility384 g/LALOGPS
logP-0.12ALOGPS
logP-0.11ChemAxon
logS0.51ALOGPS
pKa (Strongest Acidic)4.55ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity28.1 m³·mol⁻¹ChemAxon
Polarizability11.75 ųChemAxon
Number of Rings0ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
HMDB IDHMDB0000754
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB007451
KNApSAcK IDNot Available
Chemspider ID62571
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkBeta-Hydroxy_beta-methylbutyric_acid
METLIN ID5722
PubChem Compound69362
PDB IDNot Available
ChEBI ID37084
Good Scents IDrw1687381
References
General References
  1. Boulat O, Gradwohl M, Matos V, Guignard JP, Bachmann C: Organic acids in the second morning urine in a healthy Swiss paediatric population. Clin Chem Lab Med. 2003 Dec;41(12):1642-58. [PubMed:14708889 ]
  2. Guneral F, Bachmann C: Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem. 1994 Jun;40(6):862-6. [PubMed:8087979 ]
  3. Mock DM, Stadler DD: Conflicting indicators of biotin status from a cross-sectional study of normal pregnancy. J Am Coll Nutr. 1997 Jun;16(3):252-7. [PubMed:9176832 ]
  4. Baykal T, Gokcay GH, Ince Z, Dantas MF, Fowler B, Baumgartner MR, Demir F, Can G, Demirkol M: Consanguineous 3-methylcrotonyl-CoA carboxylase deficiency: early-onset necrotizing encephalopathy with lethal outcome. J Inherit Metab Dis. 2005;28(2):229-33. [PubMed:15877210 ]
  5. Amberg A, Rosner E, Dekant W: Biotransformation and kinetics of excretion of tert-amyl-methyl ether in humans and rats after inhalation exposure. Toxicol Sci. 2000 Jun;55(2):274-83. [PubMed:10828258 ]
  6. Schurmann M, Engelbrecht V, Lohmeier K, Lenard HG, Wendel U, Gartner J: Cerebral metabolic changes in biotinidase deficiency. J Inherit Metab Dis. 1997 Nov;20(6):755-60. [PubMed:9427142 ]
  7. Sealey WM, Teague AM, Stratton SL, Mock DM: Smoking accelerates biotin catabolism in women. Am J Clin Nutr. 2004 Oct;80(4):932-5. [PubMed:15447901 ]
  8. Jakobs C, Sweetman L, Nyhan WL, Packman S: Stable isotope dilution analysis of 3-hydroxyisovaleric acid in amniotic fluid: contribution to the prenatal diagnosis of inherited disorders of leucine catabolism. J Inherit Metab Dis. 1984;7(1):15-20. [PubMed:6429435 ]
  9. Santer R, Muhle H, Suormala T, Baumgartner ER, Duran M, Yang X, Aoki Y, Suzuki Y, Stephani U: Partial response to biotin therapy in a patient with holocarboxylase synthetase deficiency: clinical, biochemical, and molecular genetic aspects. Mol Genet Metab. 2003 Jul;79(3):160-6. [PubMed:12855220 ]
  10. Rodriguez JM, Ruiz-Sala P, Ugarte M, Penalva MA: Fungal metabolic model for 3-methylcrotonyl-CoA carboxylase deficiency. J Biol Chem. 2004 Feb 6;279(6):4578-87. Epub 2003 Nov 11. [PubMed:14612443 ]
  11. Stratton SL, Bogusiewicz A, Mock MM, Mock NI, Wells AM, Mock DM: Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans. Am J Clin Nutr. 2006 Aug;84(2):384-8. [PubMed:16895887 ]
  12. Mock DM, Mock NI, Nelson RP, Lombard KA: Disturbances in biotin metabolism in children undergoing long-term anticonvulsant therapy. J Pediatr Gastroenterol Nutr. 1998 Mar;26(3):245-50. [PubMed:9523856 ]
  13. Mock DM, Stratton SL, Horvath TD, Bogusiewicz A, Matthews NI, Henrich CL, Dawson AM, Spencer HJ, Owen SN, Boysen G, Moran JH: Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans. J Nutr. 2011 Nov;141(11):1925-30. doi: 10.3945/jn.111.146126. Epub 2011 Sep 14. [PubMed:21918059 ]