Human Metabolome Database: Showing metabocard for 2-Methyl-3-hydroxybutyric acid (HMDB0000354)

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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (2) Show 2 proteins XML

enzymes (2) Show 2 proteins

Record Information

Version

4.0

Status

Detected and Quantified

Creation Date

2005-11-16 15:48:42 UTC

Update Date

2020-02-27 20:30:37 UTC

HMDB ID

HMDB0000354

Secondary Accession Numbers

HMDB0000420
HMDB0000605
HMDB0002187
HMDB00354
HMDB00420
HMDB00605
HMDB02187

Metabolite Identification

Common Name

2-Methyl-3-hydroxybutyric acid

Description

3-Hydroxy-2-methyl-butanoic acid (HMBA) is a normal urinary metabolite involved in the isoleucine catabolism, as well as presumably beta-oxidation of fatty acids and ketogenesis, excreted in abnormally high amounts in beta-ketothiolase deficiency, which is a genetic disorder. Differences in the enantiomeric ratio of HMBA may originate from the enantioselectivity of different enzyme systems (PMID 10755375 ).

Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Value	Source
2-Methyl-3-hydroxybutanoic acid	ChEBI
3-Hydroxy-2-methylbutyric acid	ChEBI
2-Methyl-3-hydroxybutanoate	Generator
3-Hydroxy-2-methylbutyrate	Generator
2-Methyl-3-hydroxybutyrate	Generator
3-Hydroxy-2-methyl-butyrate	HMDB
3-Hydroxy-2-methyl-butyric acid	HMDB
3-Hydroxy-2-methylbutanoate	HMDB
3-Hydroxy-2-methylbutanoic acid	HMDB
a-Methyl-b-hydroxybutyrate	HMDB
a-Methyl-b-hydroxybutyric acid	HMDB
alpha-Methyl-beta-hydroxybutyrate	HMDB
alpha-Methyl-beta-hydroxybutyric acid	HMDB
Nilate	HMDB
Nilic acid	HMDB
2-Methyl-3-hydroxybutyric acid, (R-(r,s))-isomer	HMDB

Chemical Formula

C₅H₁₀O₃

Average Molecular Weight

118.1311

Monoisotopic Molecular Weight

118.062994186

IUPAC Name

3-hydroxy-2-methylbutanoic acid

Traditional Name

nilic acid

CAS Registry Number

473-86-9

SMILES

CC(O)C(C)C(O)=O

InChI Identifier

InChI=1S/C5H10O3/c1-3(4(2)6)5(7)8/h3-4,6H,1-2H3,(H,7,8)

InChI Key

VEXDRERIMPLZLU-UHFFFAOYSA-N

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.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Fatty Acyls

Sub Class

Fatty acids and conjugates

Direct Parent

Hydroxy fatty acids

Alternative Parents

Substituents

Beta-hydroxy acid
Branched fatty acid
Hydroxy fatty acid
Short-chain hydroxy acid
Methyl-branched fatty acid
Hydroxy acid
Secondary alcohol
Monocarboxylic acid or derivatives
Carboxylic acid
Carboxylic acid derivative
Organooxygen compound
Alcohol
Carbonyl group
Hydrocarbon derivative
Organic oxide
Organic oxygen compound
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

3-hydroxy monocarboxylic acid (CHEBI:37051 )
Hydroxy fatty acids (LMFA01050391 )

Ontology

Disposition

Route of exposure:

Enteral:

Ingestion

Source:

Biological:

Animal

Biological location:

Subcellular:

Biofluid and excreta:

Urine

Process

Naturally occurring process:

Biological process:

Biochemical process:

Biochemical pathway:

Lipid metabolism pathway

Chemical reaction:

Lipid peroxidation

Role

Industrial application:

Food and nutrition

Biological role:

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	336 g/L	ALOGPS
logP	-0.13	ALOGPS
logP	0.16	ChemAxon
logS	0.45	ALOGPS
pKa (Strongest Acidic)	4.51	ChemAxon
pKa (Strongest Basic)	-2.8	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	57.53 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	28.04 m³·mol⁻¹	ChemAxon
Polarizability	11.83 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0097-9100000000-4296c67313a78a015074	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-00ds-9610000000-ea139d8674dafe6ab92a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0uxr-3900000000-43c640882c221c34cff4	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0zfr-9500000000-f67232e28fb95b61d1f2	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9000000000-da7c5873617fe20d6385	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-014i-5900000000-bab83930d1557839e6f7	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-05fr-9100000000-50701029b9e5b3af2fbf	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4i-9000000000-dd1dac699c164a7b71f5	Spectrum

Biological Properties

Cellular Locations

Cytoplasm (predicted from logP)

Biospecimen Locations

Urine

Tissue Locations

Not Available

Pathways

Not Available

Name	SMPDB/Pathwhiz	KEGG

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Urine	Detected and Quantified	<10 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	28853722	details
Urine	Detected but not Quantified		Adult (>18 years old)	Both	Normal	24023812	details
Urine	Detected and Quantified	5.0 (1.0-9.0) umol/mmol creatinine	Children (1-13 years old)	Both	Normal	Geigy Scientific ...	details
Urine	Detected and Quantified	0-0.8 umol/mmol creatinine	Infant (0-1 year old)	Male	Normal	31963255	details
Urine	Detected and Quantified	0-1.2 umol/mmol creatinine	Infant (0-1 year old)	Male	Normal	31963255	details
Urine	Detected and Quantified	0-1.8 umol/mmol creatinine	Infant (0-1 year old)	Female	Normal	31963255	details
Urine	Detected and Quantified	0-4.1 umol/mmol creatinine	Infant (0-1 year old)	Female	Normal	31963255	details
Urine	Detected and Quantified	<30 umol/mmol creatinine	Children (1 - 18 years old)	Both	Normal	BC Children's Hos...	details
Urine	Detected but not Quantified		Adult (>18 years old)	Both	Normal	28157703	details
Urine	Detected and Quantified	4.2 (1.6-6.7) umol/mmol creatinine	Adult (>18 years old)	Both	Normal	24023812	details
Urine	Detected and Quantified	0.1 (0.1-4.1) umol/mmol creatinine	Newborn (0-30 days old)	Both	Normal	8087979	details
Urine	Detected and Quantified	0.1 (0.1-5.9) umol/mmol creatinine	Infant (0-1 year old)	Both	Normal	8087979	details
Urine	Detected and Quantified	1.5 (0.1-7.0) umol/mmol creatinine	Children (1-13 years old)	Both	Normal	8087979	details
Urine	Detected and Quantified	1.7 (0.6-2.5) umol/mmol creatinine	Children (1-13 years old)	Both	Normal	8087979	details
Urine	Detected and Quantified	1.2 (0.1-3.8) umol/mmol creatinine	Adolescent (13-18 years old)	Both	Normal	8087979	details
Urine	Detected and Quantified	4.0 (1.3-6.2) umol/mmol creatinine	Adult (>18 years old)	Both	Normal	24023812	details
Urine	Detected and Quantified	12-May umol/mmol creatinine	Not Specified	Not Specified	Normal	16148061	details

Abnormal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Urine	Detected and Quantified	160.2-405.7 umol/mmol creatinine	Children (1-13 years old)	Male	Beta-ketothiolase deficiency	23430882	details
Urine	Detected and Quantified	441 umol/mmol creatinine	Newborn (0-30 days old)	Not Available	Beta-ketothiolase deficiency	25689098	details
Urine	Detected and Quantified	370.837-809.510 umol/mmol creatinine	Children (1 - 13 years old)	Female	Ketosis	B. Middleton et a...	details
Urine	Detected and Quantified	1 umol/mmol creatinine	Adult (>18 years old)	Not Specified	Propionic acidemia	28853722	details
Urine	Detected and Quantified	5.5 (0.0-11.0) umol/mmol creatinine	Adult (>18 years old)	Both	Beta-ketothiolase deficiency	MetaGene: Metabol...	details
Urine	Detected and Quantified	2300.0 (200.0-4400.0) umol/mmol creatinine	Children (1-13 years old)	Both	Beta-Ketothiolase deficiency	MetaGene: Metabol...	details
Urine	Detected but not Quantified		Adult (>18 years old)	Both	Bladder cancer	28157703	details
Urine	Detected and Quantified	99 umol/mmol creatinine	Children (1-13 years old)	Female	2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency	16148061	details
Urine	Detected and Quantified	89-226 umol/mmol creatinine	Infant (0-1 year old)	Male	2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency	16148061	details

Associated Disorders and Diseases

Disease References

Beta-ketothiolase deficiency
Fukao T, Maruyama S, Ohura T, Hasegawa Y, Toyoshima M, Haapalainen AM, Kuwada N, Imamura M, Yuasa I, Wierenga RK, Yamaguchi S, Kondo N: Three Japanese Patients with Beta-Ketothiolase Deficiency Who Share a Mutation, c.431A>C (H144P) in ACAT1 : Subtle Abnormality in Urinary Organic Acid Analysis and Blood Acylcarnitine Analysis Using Tandem Mass Spectrometry. JIMD Rep. 2012;3:107-15. doi: 10.1007/8904_2011_72. Epub 2011 Sep 6. [PubMed:23430882 ] Scolamiero E, Cozzolino C, Albano L, Ansalone A, Caterino M, Corbo G, di Girolamo MG, Di Stefano C, Durante A, Franzese G, Franzese I, Gallo G, Giliberti P, Ingenito L, Ippolito G, Malamisura B, Mazzeo P, Norma A, Ombrone D, Parenti G, Pellecchia S, Pecce R, Pierucci I, Romanelli R, Rossi A, Siano M, Stoduto T, Villani GR, Andria G, Salvatore F, Frisso G, Ruoppolo M: Targeted metabolomics in the expanded newborn screening for inborn errors of metabolism. Mol Biosyst. 2015 Jun;11(6):1525-35. doi: 10.1039/c4mb00729h. [PubMed:25689098 ] G.Frauendienst-Egger, Friedrich K. Trefz (2017). MetaGene: Metabolic & Genetic Information Center (MIC: http://www.metagene.de). METAGENE consortium.
Ketosis
B. Middleton et al. (1986). B. Middleton et al. 3-Ketothiolase deficiency. Eur J Pediatr (1986) 144:586-589. Eur J Pediatr.
Propionic acidemia
Riemersma M, Hazebroek MR, Helderman-van den Enden ATJM, Salomons GS, Ferdinandusse S, Brouwers MCGJ, van der Ploeg L, Heymans S, Glatz JFC, van den Wijngaard A, Krapels IPC, Bierau J, Brunner HG: Propionic acidemia as a cause of adult-onset dilated cardiomyopathy. Eur J Hum Genet. 2017 Nov;25(11):1195-1201. doi: 10.1038/ejhg.2017.127. Epub 2017 Aug 30. [PubMed:28853722 ]
2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency
Perez-Cerda C, Garcia-Villoria J, Ofman R, Sala PR, Merinero B, Ramos J, Garcia-Silva MT, Beseler B, Dalmau J, Wanders RJ, Ugarte M, Ribes A: 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: an X-linked inborn error of isoleucine metabolism that may mimic a mitochondrial disease. Pediatr Res. 2005 Sep;58(3):488-91. [PubMed:16148061 ]

Associated OMIM IDs

203750 (Beta-ketothiolase deficiency)
606054 (Propionic acidemia)
300438 (2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency)

External Links

DrugBank ID

Not Available

Phenol Explorer Compound ID

Not Available

FoodDB ID

FDB021977

KNApSAcK ID

Not Available

Chemspider ID

141015

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Not Available

METLIN ID

3786

PubChem Compound

160471

PDB ID

Not Available

ChEBI ID

37051

Food Biomarker Ontology

Not Available

VMH ID

Not Available

References

Synthesis Reference

Inoue, Yoshio; Sano, Fumitaka; Nakamura, Kazuhiro; Yoshie, Naoko; Saito, Yuji; Satoh, Hiroyasu; Mino, Takashi; Matsuo, Tomonori; Doi, Yoshiharu. Microstructure of copoly(3-hydroxyalkanoates) produced in the anaerobic-aerobic activated sludge process. Polymer International (1996), 39(3), 183-9.

Material Safety Data Sheet (MSDS)

Not Available

General References

Jakobs C, Sweetman L, Nyhan WL: Hydroxy acid metabolites of branched-chain amino acids in amniotic fluid. Clin Chim Acta. 1984 Jul 16;140(2):157-66. [PubMed:6467607 ]
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 ]
Sutton VR, O'Brien WE, Clark GD, Kim J, Wanders RJ: 3-Hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 2003;26(1):69-71. [PubMed:12872843 ]
Landaas S: Accumulation of 3-hydroxyisobutyric acid, 2-methyl-3-hydroxybutyric acid and 3-hydroxyisovaleric acid in ketoacidosis. Clin Chim Acta. 1975 Oct 15;64(2):143-54. [PubMed:126826 ]
Heil M, Podebrad F, Prado E, Beck T, Mosand A, Sewell AC, Bohles H, Lehnert W: Enantioselective analysis of ketone bodies in patients with beta-ketothiolase deficiency, medium-chain acyl coenzyme A dehydrogenase deficiency and ketonemic vomiting. J Chromatogr B Biomed Sci Appl. 2000 Mar 10;739(2):313-24. [PubMed:10755375 ]

Enzymes

Enzyme Details

1. Sulfotransferase family cytosolic 2B member 1

General function:: Involved in sulfotransferase activity
Specific function:: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs and xenobiotic compounds. Sulfonation increases the water solubility of most compounds, and therefore their renal excretion, but it can also result in bioactivation to form active metabolites. Sulfates hydroxysteroids like DHEA. Isoform 1 preferentially sulfonates cholesterol, and isoform 2 avidly sulfonates pregnenolone but not cholesterol.
Gene Name:: SULT2B1
Uniprot ID:: O00204
Molecular weight:: 39598.595

Reactions

2-Methyl-3-hydroxybutyric acid → 2-methyl-3-(sulfooxy)butanoic acid	details

Enzyme Details

2. UDP-glucuronosyltransferase 1-1

General function:: Involved in transferase activity, transferring hexosyl groups
Specific function:: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.
Gene Name:: UGT1A1
Uniprot ID:: P22309
Molecular weight:: 59590.91

Reactions

2-Methyl-3-hydroxybutyric acid → 6-[(1-carboxy-1-methylpropan-2-yl)oxy]-3,4,5-trihydroxyoxane-2-carboxylic acid	details
2-Methyl-3-hydroxybutyric acid → 3,4,5-trihydroxy-6-[(3-hydroxy-2-methylbutanoyl)oxy]oxane-2-carboxylic acid	details

Showing metabocard for 2-Methyl-3-hydroxybutyric acid (HMDB0000354)

Structure for HMDB0000354 (2-Methyl-3-hydroxybutyric acid)

Enzymes

Reactions

Reactions