MiMeDB: Showing metabocard for (S)-3-methyl-2-oxovaleric acid (MMDBc0032933)

Microbial

Human

Plant

Animal

Record Information

Version

2.0

Status

Detected and Quantified

Creation Date

2021-11-19 04:27:54 UTC

Update Date

2024-04-30 19:55:10 UTC

Metabolite ID

MMDBc0032933

Metabolite Identification

Common Name

(S)-3-methyl-2-oxovaleric acid

Description

3-Methyl-2-oxovaleric acid (CAS: 1460-34-0) is an abnormal metabolite that arises from the incomplete breakdown of branched-chain amino acids. 3-Methyl-2-oxovaleric acid is a neurotoxin, an acidogen, and a metabotoxin. A neurotoxin causes damage to nerve cells and nerve tissues. 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-methyl-2-oxovaleric acid are associated with maple syrup urine disease. MSUD is a metabolic disorder caused by a deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), leading to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products (ketoacids) in the blood and urine. The symptoms of MSUD often show in infancy and lead to severe brain damage if untreated. MSUD may also present later depending on the severity of the disease. If left untreated in older individuals, during times of metabolic crisis, symptoms of the condition include uncharacteristically inappropriate, extreme, or erratic behaviour and moods, hallucinations, anorexia, weight loss, anemia, diarrhea, vomiting, dehydration, lethargy, oscillating hypertonia and hypotonia, ataxia, seizures, hypoglycemia, ketoacidosis, opisthotonus, pancreatitis, rapid neurological decline, and coma. In maple syrup urine disease, the brain concentration of branched-chain ketoacids can increase 10- to 20-fold. This leads to a depletion of glutamate and a consequent reduction in the concentration of brain glutamine, aspartate, alanine, and other amino acids. The result is a compromise of energy metabolism because of a failure of the malate-aspartate shuttle and a diminished rate of protein synthesis (PMID: 15930465 ). 3-Methyl-2-oxovaleric acid is a keto-acid, which is a subclass of organic acids. 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 untreated MSUD. Many affected children with organic acidemias experience intellectual disability or delayed development.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Not Available

Molecular Formula

C₆H₁₀O₃

Average Mass

130.1418

Monoisotopic Mass

130.062994186

IUPAC Name

Not Available

Traditional Name

Not Available

CAS Registry Number

1460-34-0

SMILES

Not Available

InChI Identifier

InChI=1S/C6H10O3/c1-3-4(2)5(7)6(8)9/h4H,3H2,1-2H3,(H,8,9)/t4-/m0/s1

InChI Key

JVQYSWDUAOAHFM-BYPYZUCNSA-N

Chemical Taxonomy

Functional Ontology

Not Available

Physical Properties

State

Solid

Predicted Properties

Not Available

Spectra

Not Available

Chromatographic Retention Times and Retention Indices

Retention Times

Chromatography Type	Technique	Column	Deposition Date	Retention Time (s)
Liquid Chromatography	HILIC	Waters Acquity UPLC-BEH Amide column (eluted)	2025-10-24	276.4
Liquid Chromatography	HILIC	Accucore 150 Amide HILIC (eluted)	2025-10-24	36.5
Liquid Chromatography	Reversed-phase	Hypersil Gold 1.9 µm C18 (eluted)	2025-10-24	364.5
Liquid Chromatography	Reversed-phase	Agilent Zorbax Eclipse Plus C18 (2.1 mm x 150 mm, 3.5 um) (eluted)	2025-10-24	518.5
Liquid Chromatography	Reversed-phase	XBridge C18 3.5u 2.1x50 mm (eluted)	2025-10-24	454.4
Liquid Chromatography	Reversed-phase	Ascentis Express C18 (void)	2025-10-24	415.3
Liquid Chromatography	Reversed-phase	Waters ACQUITY UPLC HSS T3 C18 (eluted)	2025-10-24	1588.8
Liquid Chromatography	HILIC	Merck SeQuant ZIC-HILIC (void)	2025-10-24	118.4
Liquid Chromatography	HILIC	Merck SeQuant ZIC-pHILIC (eluted)	2025-10-24	590.5
Liquid Chromatography	Reversed-phase	Waters ACQUITY UPLC HSS T3 C18 (eluted)	2025-10-24	388.4
Liquid Chromatography	HILIC	Merck SeQuant ZIC-HILIC (eluted)	2025-10-24	331.7
Liquid Chromatography	Reversed-phase	Waters ACQUITY UPLC HSS T3 C18 (eluted)	2025-10-24	259.1
Liquid Chromatography	Reversed-phase	Waters ACQUITY UPLC BEH C18 (eluted)	2025-10-24	132.3
Liquid Chromatography	HILIC	Merck SeQuant ZIC-pHILIC column (eluted)	2025-10-24	86.7
Liquid Chromatography	HILIC	Merck SeQuant ZIC-pHILIC column (eluted)	2025-10-24	465.4
Liquid Chromatography	Reversed-phase	Waters ACQUITY UPLC BEH C18 (eluted)	2025-10-24	103.2
Liquid Chromatography	Reversed-phase	Waters ACQUITY UPLC BEH C18 (eluted)	2025-10-24	341.8
Liquid Chromatography	Reversed-phase	Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex (eluted)	2025-10-24	1191.0
Liquid Chromatography	Reversed-phase	Waters Atlantis T3 (2.1 x 150 mm, 5 um) (eluted)	2025-10-24	907.7

Retention Indices

Chromatography Type	Peak Label	SMILES	Stationary Phase	Deposition Date	Retention Index
Gas Chromatography	(S)-3-methyl-2-oxovaleric acid_TMS_1	CC[C@H](C)C(=O)C(=O)O[Si](C)(C)C	standard non polar	2025-10-24	1735.43
Gas Chromatography	(S)-3-methyl-2-oxovaleric acid_TMS_2	CCC(C)=C(O[Si](C)(C)C)C(=O)O	standard non polar	2025-10-24	1921.76
Gas Chromatography	(S)-3-methyl-2-oxovaleric acid_TMS_3	CCC(C)=C(O[Si](C)(C)C)C(=O)O[Si](C)(C)C	standard non polar	2025-10-24	1973.42
Gas Chromatography	(S)-3-methyl-2-oxovaleric acid_TMS_1	CC[C@H](C)C(=O)C(=O)O[Si](C)(C)C	standard polar	2025-10-24	1898.58
Gas Chromatography	(S)-3-methyl-2-oxovaleric acid_TMS_2	CCC(C)=C(O[Si](C)(C)C)C(=O)O	standard polar	2025-10-24	2117.03
Gas Chromatography	(S)-3-methyl-2-oxovaleric acid_TMS_3	CCC(C)=C(O[Si](C)(C)C)C(=O)O[Si](C)(C)C	standard polar	2025-10-24	1955.23

Biological Properties

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biospecimen Locations

Blood
Cerebrospinal Fluid (CSF)
Feces
Placenta
Prostate
Saliva
Urine

Tissue Locations

Placenta
Prostate

Associated OMIM IDs

114500 (Colorectal cancer)
610247 (Eosinophilic esophagitis)

Human Proteins and Enzymes

Protein ID	Protein Name	Protein Type	Uniprot ID	Species
MMDBp0191969	2-oxoisovalerate dehydrogenase subunit beta, mitochondrial	Enzyme	P21953	Homo sapiens
MMDBp0191970	2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial	Unknown	P12694	Homo sapiens
MMDBp0191971	Branched-chain-amino-acid aminotransferase, cytosolic	Enzyme	P54687	Homo sapiens
MMDBp0192169	Branched-chain-amino-acid aminotransferase, mitochondrial	Enzyme	O15382	Homo sapiens
MMDBp0195052	L-amino-acid oxidase	Unknown	Q96RQ9	Homo sapiens

Human Pathways

Pathways

Name	SMPDB/PathBank

Microbial Pathways

Pathways

Name	SMPDB/PathBank	Species
Isoleucine Biosynthesis
Leucine Biosynthesis
Secondary Metabolites: Leucine Biosynthesis
Secondary Metabolites: Valine and L-Leucine Biosynthesis from Pyruvate

Metabolic Reactions

Reactions

This table shows at most 20 reactions. For the full list of associated reactions:

See All Associated Reactions

Reaction ID	Precursor	Product	Enzyme	Reaction Type	Data Source	Reference
MMDBr0019969	L-Isoleucine	L-Glutamic acid	Branched-chain-amino-acid aminotransferase, mitochondrial	Amine group addition	PathBank	31602464
MMDBr0019970	L-Isoleucine	(S)-3-methyl-2-oxovaleric acid	Branched-chain-amino-acid aminotransferase, cytosolic	Amine group addition	PathBank	31602464
MMDBr0019971	(S)-3-methyl-2-oxovaleric acid	2-Methylbutanal	Pyruvate decarboxylase isozyme 1	Carboxylation	PathBank	31602464

Health Effects and Bioactivity

Health Outcome/Bioactivity	Metabolite Response/Effect	Evidence Type	Host and Biospecimen	Data Source	Reference
Maple syrup urine disease	Increased	Association	Human Blood	HMDB	10472531
Maple syrup urine disease	Increased	Association	Human Urine	HMDB	10472531
Eosinophilic esophagitis		Association	Human Urine	HMDB	Slae, M., Huynh, H., Wishart, D.S. (2014). Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)
Maple syrup urine disease		Association	Human Cerebrospinal Fluid (CSF)	HMDB	Peritoneal dialysis in maple-syrup-urine disease: Studies on branched-chain amino and keto acids. Eur J Pediatr (1980) 134: 57. https://doi.org/10.1007/BF00442404
Maple syrup urine disease		Association	Human Blood	HMDB	Peritoneal dialysis in maple-syrup-urine disease: Studies on branched-chain amino and keto acids. Eur J Pediatr (1980) 134: 57. https://doi.org/10.1007/BF00442404

Microbial Sources

Superkingdom/Kingdom	Phylum	Total species	Hosts and Body Sites	Microbial Links
Eukaryota/Fungi	Ascomycota	1	Human feces; Human saliva	Unknown
Bacteria/Eubacteria	Firmicutes	499	Human feces; Human pleural fluid plaque; Pig ; Human sputum; Human ; Human subgingival plaque; Human saliva; Human urine; Human mucosa; Human supragingival plaque; Cattle	Metabolic reconstruction
Bacteria/Eubacteria	Proteobacteria	274	Human feces; Human sputum; Human ; Human unknown; Pig ; Human pleural fluid plaque; Human dental plaque; Human nasal swab	Metabolic reconstruction
Bacteria/Eubacteria	Actinobacteria	155	Human feces; Human sputum; Human bronchial brush; Human nasopharyngeal swab; Human pleural fluid plaque; Human dental plaque; Human	Metabolic reconstruction
Bacteria/Eubacteria	Verrucomicrobia	1	Human ; Human feces	Metabolic reconstruction
Bacteria/Eubacteria	Bacteroidetes	125	Human feces; Human appendix biopsy; Human ; Human saliva	Metabolic reconstruction
Bacteria/Eubacteria	Synergistetes	5	Human feces	Metabolic reconstruction
Bacteria	Firmicutes	2	Human feces; Human pleural fluid plaque; Pig ; Human sputum; Human ; Human subgingival plaque; Human saliva; Human urine; Human mucosa; Human supragingival plaque; Cattle	Metabolic reconstruction
Bacteria/Eubacteria	Spirochaetes	2	Human feces	Metabolic reconstruction
Archaea	Thaumarchaeota	2		Metabolic reconstruction
Bacteria/Eubacteria	Fusobacteria	15	Human feces; Human	Metabolic reconstruction
Archaea	Euryarchaeota	8		Metabolic reconstruction
Bacteria/Eubacteria	Candidatus melainabacteria	1	Human feces	Metabolic reconstruction
Bacteria/Eubacteria	Tenericutes	4	Human feces	Metabolic reconstruction
Bacteria/Eubacteria	Planctomycetes	2	Human feces	Metabolic reconstruction
Archaea	Crenarchaeota	2		Metabolic reconstruction

Exposure Sources

Other Exposures

Source Type	Data Source	Reference
Food Additive	U.S. Food and Drug Administration	FDA

Host Biospecimen and Location

Host and Biospecimen	Status	Mean	Std	Min	Max	Units	Age	Sex	Health Condition	Data Source	Reference
Human Blood	Detected and Quantified	142.0	9.0			uM	Adult (>18 years old)	Both	Maple syrup urine disease (MSUD)	HMDB	10472531
Human Urine	Detected and Quantified	209.0	35.0			umol/mmol creatinine	Adult (>18 years old)	Both	Maple syrup urine disease (MSUD)	HMDB	10472531
Human Urine	Detected and Quantified	0.3				umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	21388201
Human Urine	Detected and Quantified			0	7	umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	HMDB	31506554
Human Urine	Detected and Quantified	0.24		0.11	0.55	umol/mmol creatinine	Adult (>18 years old)	Not Specified	Normal	HMDB	9869358
Human Urine	Detected and Quantified			0.53	0.88	umol/mmol creatinine	Adult (>18 years old)	Male	Normal	HMDB	27012787
Human Urine	Detected and Quantified	0.54		0.12	1.42	umol/mmol creatinine	Adult (>18 years old)	Female	Normal	HMDB	9869358
Human Urine	Detected and Quantified			0.55	0.95	umol/mmol creatinine	Adult (>18 years old)	Female	Normal	HMDB	27012787
Human Blood	Detected and Quantified	18.0		8.0	31.0	uM	Adult (>18 years old)	Both	Normal	HMDB	8412012
Human Cerebrospinal fluid (csf)	Detected and Quantified	2.0	2.0			uM	Adult (>18 years old)	Both	Normal	HMDB	8412012
Human Urine	Detected and Quantified	2.2		0.4	4.8	umol/mmol creatinine	Adult (>18 years old)	Both	Normal	HMDB	24023812
Human Urine	Detected and Quantified	4.333	3.83			umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Eosinophilic esophagitis	HMDB	Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)
Human Cerebrospinal fluid (csf)	Detected and Quantified	101				uM	Children (1-13 years old)	Female	Maple syrup urine disease	HMDB	Peritoneal dialysis in maple-syrup-urine disease: Studies on branched-chain amino and keto acids. Eur J Pediatr (1980) 134: 57. https://doi.org/10.1007/BF00442404
Human Blood	Detected and Quantified	368				uM	Children (1-13 years old)	Female	Maple syrup urine disease	HMDB	Peritoneal dialysis in maple-syrup-urine disease: Studies on branched-chain amino and keto acids. Eur J Pediatr (1980) 134: 57. https://doi.org/10.1007/BF00442404
Human Urine	Detected and Quantified	6.005				umol/mmol creatinine	Children (1 - 13 years old)	Not Specified	Normal	HMDB	Analysis of 30 normal pediatric urine samples via NMR spectroscopy (unpublished work)
Human Blood	Detected and Quantified	22.7	4.6			uM	Adult (>18 years old)	Both	Normal	HMDB	Geigy Scientific Tables, 8th Rev edition, pp. 130. Edited by C. Lentner, West Cadwell, N.J.: Medical education Div., Ciba-Geigy Corp. Basel, Switzerland c1981-1992.
Human Placenta	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Prostate	Detected but not Quantified						Not Specified	Not Specified	Normal	HMDB	34986597
Human Urine	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22932811
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Saliva	Detected but not Quantified						Adult (>18 years old)	Male	Normal	HMDB	22308371
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	18052033
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	27543620
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	25037050
Human Feces	Detected but not Quantified						Adult (>18 years old)	Not Specified	Normal	HMDB	25985090
Human Feces	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	29808030
Human Urine	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057
Human Blood	Detected but not Quantified						Adult (>18 years old)	Both	Normal	HMDB	32966057

External Links

HMDB ID

Not Available

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

Not Available

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

Not Available

PubChem Compound

Not Available

PDB ID

Not Available

ChEBI ID

Not Available

Food Biomarker Ontology

Not Available

CMMC Knowledgebase

Not Available

General References

Przyrembel H, Bremer HJ, Duran M, Bruinvis L, Ketting D, Wadman SK, Baumgartner R, Irle U, Bachmann C: Propionyl-CoA carboxylase deficiency with overflow of metabolites of isoleucine catabolism at all levels. Eur J Pediatr. 1979 Jan 18;130(1):1-14. doi: 10.1007/BF00441893. [PubMed:759179 ]
Wendel U, Even G, Langenbeck U, Schadewaldt P, Hummel W: Determination of (S)- and (R)-2-oxo-3-methylvaleric acid in plasma of patients with maple syrup urine disease. Clin Chim Acta. 1992 Jun 15;208(1-2):85-91. doi: 10.1016/0009-8981(92)90024-k. [PubMed:1638756 ]
Yudkoff M, Daikhin Y, Nissim I, Horyn O, Luhovyy B, Luhovyy B, Lazarow A, Nissim I: Brain amino acid requirements and toxicity: the example of leucine. J Nutr. 2005 Jun;135(6 Suppl):1531S-8S. doi: 10.1093/jn/135.6.1531S. [PubMed:15930465 ]
Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [PubMed:19212411 ]
Elshenawy S, Pinney SE, Stuart T, Doulias PT, Zura G, Parry S, Elovitz MA, Bennett MJ, Bansal A, Strauss JF 3rd, Ischiropoulos H, Simmons RA: The Metabolomic Signature of the Placenta in Spontaneous Preterm Birth. Int J Mol Sci. 2020 Feb 4;21(3). pii: ijms21031043. doi: 10.3390/ijms21031043. [PubMed:32033212 ]

Showing metabocard for (S)-3-methyl-2-oxovaleric acid (MMDBc0032933)

MOL for #<Metabolite:0x00007f9af0bd8200>

3D MOL for #<Metabolite:0x00007f9af0bd8200>

3D SDF for #<Metabolite:0x00007f9af0bd8200>

3D-SDF for #<Metabolite:0x00007f9af0bd8200>

PDB for #<Metabolite:0x00007f9af0bd8200>

3D PDB for #<Metabolite:0x00007f9af0bd8200>

SMILES for #<Metabolite:0x00007f9af0bd8200>

INCHI for #<Metabolite:0x00007f9af0bd8200>

Structure for #<Metabolite:0x00007f9af0bd8200>

3D Structure for #<Metabolite:0x00007f9af0bd8200>