Human Metabolome Database: Showing metabocard for 3-Hydroxybutyrylcarnitine (HMDB0013127)

You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.

Jump To Section:

Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References XML

Record Information

Version

4.0

Status

Detected and Quantified

Creation Date

2009-11-02 23:11:25 UTC

Update Date

2021-04-12 19:29:44 UTC

HMDB ID

HMDB0013127

Secondary Accession Numbers

HMDB13127

Metabolite Identification

Common Name

3-Hydroxybutyrylcarnitine

Description

3-Hydroxybutyrylcarnitine is an acylcarnitine. More specifically, it is an 3-hydroxybutyric acid ester of carnitine. Acylcarnitines were first discovered more than 70 year ago (PMID: 13825279 ). It is believed that there are more than 1000 types of acylcarnitines in the human body. The general role of acylcarnitines is to transport acyl-groups (organic acids and fatty acids) from the cytoplasm into the mitochondria so that they can be broken down to produce energy. This process is known as beta-oxidation. According to a recent review [Dambrova et al. 2021, Physiological Reviews], acylcarnitines (ACs) can be classified into 9 different categories depending on the type and size of their acyl-group: 1) short-chain ACs; 2) medium-chain ACs; 3) long-chain ACs; 4) very long-chain ACs; 5) hydroxy ACs; 6) branched chain ACs; 7) unsaturated ACs; 8) dicarboxylic ACs and 9) miscellaneous ACs. Short-chain ACs have acyl-groups with two to five carbons (C2-C5), medium-chain ACs have acyl-groups with six to thirteen carbons (C6-C13), long-chain ACs have acyl-groups with fourteen to twenty once carbons (C14-C21) and very long-chain ACs have acyl groups with more than 22 carbons. 3-Hydroxybutyrylcarnitine is therefore classified as a short chain AC. As a short-chain acylcarnitine 3-hydroxybutyrylcarnitine is a member of the most abundant group of carnitines in the body, comprising more than 50% of all acylcarnitines quantified in tissues and biofluids (PMID: 31920980 ). Some short-chain carnitines have been studied as supplements or treatments for a number of diseases, including neurological disorders and inborn errors of metabolism. In particular 3-hydroxybutyrylcarnitine is elevated in the blood or plasma of individuals with short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency (PMID: 11489939 , PMID: 15870679 ), prediabetes (PMID: 28505362 ), T2DM (PMID: 28505362 ), metallosis (PMID: 30271721 ), mitochondrial acetoacetyl-coa thiolase deficiency (PMID: 20157782 ), and heart failure (PMID: 25881932 ). It is also decreased in the blood or plasma of individuals with psoriasis (PMID: 33391503 ). 3-Hydroxybutyrylcarnitine is elevated in the urine of individuals with renal cell carcinoma (PMID: 29658093 ). Carnitine acetyltransferase (CrAT, EC:2.3.1.7) is responsible for the synthesis of all short-chain and short branched-chain acylcarnitines (PMID: 23485643 ). The study of acylcarnitines is an active area of research and it is likely that many novel acylcarnitines will be discovered in the coming years. It is also likely that many novel roles in health and disease will be uncovered. An excellent review of the current state of knowledge for acylcarnitines is available at [Dambrova et al. 2021, Physiological Reviews].

Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(3S)-3-{[(3R)-3-hydroxybutanoyl]oxy}-4-(trimethylazaniumyl)butanoic acid	Generator
(3S)-Hydroxybutyrylcarnitine	HMDB
(S)-3-Hydroxybutyrylcarnitine	HMDB
3-Hydroxybutyrylcarnitine	HMDB
Hydroxybutyrylcarnitine	HMDB

Chemical Formula

C₁₁H₂₁NO₅

Average Molecular Weight

247.291

Monoisotopic Molecular Weight

247.14197278

IUPAC Name

(3S)-3-{[(3R)-3-hydroxybutanoyl]oxy}-4-(trimethylazaniumyl)butanoate

Traditional Name

(3S)-3-{[(3R)-3-hydroxybutanoyl]oxy}-4-(trimethylammonio)butanoate

CAS Registry Number

1469900-92-2

SMILES

C[C@@H](O)CC(=O)O[C@@H](CC([O-])=O)C[N+](C)(C)C

InChI Identifier

InChI=1S/C11H21NO5/c1-8(13)5-11(16)17-9(6-10(14)15)7-12(2,3)4/h8-9,13H,5-7H2,1-4H3/t8-,9+/m1/s1

InChI Key

UEFRDQSMQXDWTO-BDAKNGLRSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as acyl carnitines. These are organic compounds containing a fatty acid with the carboxylic acid attached to carnitine through an ester bond.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Fatty Acyls

Sub Class

Fatty acid esters

Direct Parent

Acyl carnitines

Alternative Parents

Substituents

Acyl-carnitine
Beta-hydroxy acid
Hydroxy acid
Dicarboxylic acid or derivatives
Tetraalkylammonium salt
Quaternary ammonium salt
Secondary alcohol
Carboxylic acid salt
Carboxylic acid ester
Carboxylic acid
Carboxylic acid derivative
Organic nitrogen compound
Organic oxygen compound
Organopnictogen compound
Organic oxide
Hydrocarbon derivative
Organic salt
Organic zwitterion
Organooxygen compound
Organonitrogen compound
Carbonyl group
Amine
Alcohol
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

Not Available

Ontology

Disposition

Route of exposure:

Enteral:

Ingestion

Source:

Biological:

Animal

Biological location:

Tissue and substructures:

Placenta

Biofluid and excreta:

Cell and elements:

Extracellular

Subcellular:

Process

Naturally occurring process:

Biological process:

Chemical reaction:

Lipid peroxidation

Biochemical pathway:

Lipid metabolism pathway

Biochemical process:

Cellular process:

Cell signaling

Role

Industrial application:

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	1.1 g/L	ALOGPS
logP	-2.3	ALOGPS
logP	-4.6	ChemAxon
logS	-2.4	ALOGPS
pKa (Strongest Acidic)	4.14	ChemAxon
pKa (Strongest Basic)	-2.6	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	86.66 Å²	ChemAxon
Rotatable Bond Count	8	ChemAxon
Refractivity	83.46 m³·mol⁻¹	ChemAxon
Polarizability	25.51 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

Not Available

Biological Properties

Cellular Locations

Extracellular
Membrane

Biospecimen Locations

Blood
Feces
Urine

Tissue Locations

Placenta

Pathways

Not Available

Name	SMPDB/Pathwhiz	KEGG

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	32966057	details
Blood	Detected and Quantified	0.11 +/- 0.01 uM	Adult (>18 years old)	Both	Normal	21359215	details
Blood	Detected and Quantified	0.0960 (0.000-0.360) uM	Infant (0-1 year old)	Not Specified	Normal	11489939	details
Blood	Detected and Quantified	<0.400 uM	Infant (0-1 year old)	Not Specified	Normal	25251209	details
Blood	Detected and Quantified	0.04 +/- 0.02 uM	Adult (>18 years old)	Both	Normal	28278231	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	25037050	details
Feces	Detected and Quantified	0.6 +/- 0.36 nmol/g wet feces	Adult (>18 years old)	Both	Normal	27624970	details
Feces	Detected and Quantified	0.32 +/- 0.2 nmol/g wet feces	Adult (>18 years old)	Both	Normal	27624970	details
Urine	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Normal	32966057	details

Abnormal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Detected and Quantified	1.780 (0.920-3.0400) uM	Infant (0-1 year old)	Female	3-Hydroxyacyl-CoA dehydrogenase deficiency (SCHAD)	11489939	details
Blood	Detected and Quantified	0.200 (0.0800-0.500) uM	Infant (0-1 year old)	Not Specified	Ketosis	11489939	details
Blood	Detected and Quantified	0.180 (0.0600-0.360) uM	Infant (0-1 year old)	Not Specified	Short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency	11489939	details
Blood	Detected and Quantified	0.940-1.720 uM	Infant (0-1 year old)	Male	3-Hydroxyacyl-CoA dehydrogenase deficiency (SCHAD)	23430856	details
Blood	Detected and Quantified	0.660-0.810 uM	Infant (0-1 year old)	Male	3-Hydroxyisobutyryl-coa hydrolase deficiency	25251209	details
Feces	Detected but not Quantified	Not Quantified	Adult (>18 years old)	Both	Colorectal cancer	25037050	details

Associated Disorders and Diseases

Disease References

3-Hydroxyacyl-CoA dehydrogenase deficiency
Clayton PT, Eaton S, Aynsley-Green A, Edginton M, Hussain K, Krywawych S, Datta V, Malingre HE, Berger R, van den Berg IE: Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Invest. 2001 Aug;108(3):457-65. [PubMed:11489939 ] Popa FI, Perlini S, Teofoli F, Degani D, Funghini S, La Marca G, Rinaldo P, Vincenzi M, Antoniazzi F, Boner A, Camilot M: 3-hydroxyacyl-coenzyme a dehydrogenase deficiency: identification of a new mutation causing hyperinsulinemic hypoketotic hypoglycemia, altered organic acids and acylcarnitines concentrations. JIMD Rep. 2012;2:71-7. doi: 10.1007/8904_2011_50. Epub 2011 Sep 6. [PubMed:23430856 ]
Ketosis
Clayton PT, Eaton S, Aynsley-Green A, Edginton M, Hussain K, Krywawych S, Datta V, Malingre HE, Berger R, van den Berg IE: Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Invest. 2001 Aug;108(3):457-65. [PubMed:11489939 ]
Short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency
Clayton PT, Eaton S, Aynsley-Green A, Edginton M, Hussain K, Krywawych S, Datta V, Malingre HE, Berger R, van den Berg IE: Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Invest. 2001 Aug;108(3):457-65. [PubMed:11489939 ]
3-Hydroxyisobutyryl-coa hydrolase deficiency
Reuter MS, Sass JO, Leis T, Kohler J, Mayr JA, Feichtinger RG, Rauh M, Schanze I, Bahr L, Trollmann R, Uebe S, Ekici AB, Reis A: HIBCH deficiency in a patient with phenotypic characteristics of mitochondrial disorders. Am J Med Genet A. 2014 Dec;164A(12):3162-9. doi: 10.1002/ajmg.a.36766. Epub 2014 Sep 23. [PubMed:25251209 ]
Colorectal cancer
Goedert JJ, Sampson JN, Moore SC, Xiao Q, Xiong X, Hayes RB, Ahn J, Shi J, Sinha R: Fecal metabolomics: assay performance and association with colorectal cancer. Carcinogenesis. 2014 Sep;35(9):2089-96. doi: 10.1093/carcin/bgu131. Epub 2014 Jul 18. [PubMed:25037050 ]

Associated OMIM IDs

231530 (3-Hydroxyacyl-CoA dehydrogenase deficiency)
250620 (3-Hydroxyisobutyryl-coa hydrolase deficiency)
114500 (Colorectal cancer)

External Links

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

VMH ID

Not Available

MarkerDB ID

MDB00029837

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Not Available

General References

Simons K, Toomre D: Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9. [PubMed:11413487 ]
Watson AD: Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. Lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res. 2006 Oct;47(10):2101-11. Epub 2006 Aug 10. [PubMed:16902246 ]
Sethi JK, Vidal-Puig AJ: Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res. 2007 Jun;48(6):1253-62. Epub 2007 Mar 20. [PubMed:17374880 ]
Lingwood D, Simons K: Lipid rafts as a membrane-organizing principle. Science. 2010 Jan 1;327(5961):46-50. doi: 10.1126/science.1174621. [PubMed:20044567 ]
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 ]
FRITZ IB: Action of carnitine on long chain fatty acid oxidation by liver. Am J Physiol. 1959 Aug;197:297-304. doi: 10.1152/ajplegacy.1959.197.2.297. [PubMed:13825279 ]
Makarova E, Makrecka-Kuka M, Vilks K, Volska K, Sevostjanovs E, Grinberga S, Zarkova-Malkova O, Dambrova M, Liepinsh E: Decreases in Circulating Concentrations of Long-Chain Acylcarnitines and Free Fatty Acids During the Glucose Tolerance Test Represent Tissue-Specific Insulin Sensitivity. Front Endocrinol (Lausanne). 2019 Dec 17;10:870. doi: 10.3389/fendo.2019.00870. eCollection 2019. [PubMed:31920980 ]
Clayton PT, Eaton S, Aynsley-Green A, Edginton M, Hussain K, Krywawych S, Datta V, Malingre HE, Berger R, van den Berg IE: Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Invest. 2001 Aug;108(3):457-65. [PubMed:11489939 ]
Hussain K, Clayton PT, Krywawych S, Chatziandreou I, Mills P, Ginbey DW, Geboers AJ, Berger R, van den Berg IE, Eaton S: Hyperinsulinism of infancy associated with a novel splice site mutation in the SCHAD gene. J Pediatr. 2005 May;146(5):706-8. doi: 10.1016/j.jpeds.2005.01.032. [PubMed:15870679 ]
Zhong H, Fang C, Fan Y, Lu Y, Wen B, Ren H, Hou G, Yang F, Xie H, Jie Z, Peng Y, Ye Z, Wu J, Zi J, Zhao G, Chen J, Bao X, Hu Y, Gao Y, Zhang J, Yang H, Wang J, Madsen L, Kristiansen K, Ni C, Li J, Liu S: Lipidomic profiling reveals distinct differences in plasma lipid composition in healthy, prediabetic, and type 2 diabetic individuals. Gigascience. 2017 Jul 1;6(7):1-12. doi: 10.1093/gigascience/gix036. [PubMed:28505362 ]
Stepien KM, Abidin Z, Lee G, Cullen R, Logan P, Pastores GM: Metallosis mimicking a metabolic disorder: a case report. Mol Genet Metab Rep. 2018 Sep 25;17:38-41. doi: 10.1016/j.ymgmr.2018.09.005. eCollection 2018 Dec. [PubMed:30271721 ]
Catanzano F, Ombrone D, Di Stefano C, Rossi A, Nosari N, Scolamiero E, Tandurella I, Frisso G, Parenti G, Ruoppolo M, Andria G, Salvatore F: The first case of mitochondrial acetoacetyl-CoA thiolase deficiency identified by expanded newborn metabolic screening in Italy: the importance of an integrated diagnostic approach. J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S91-4. doi: 10.1007/s10545-009-9028-3. Epub 2010 Feb 16. [PubMed:20157782 ]
Cheng ML, Wang CH, Shiao MS, Liu MH, Huang YY, Huang CY, Mao CT, Lin JF, Ho HY, Yang NI: Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics. J Am Coll Cardiol. 2015 Apr 21;65(15):1509-20. doi: 10.1016/j.jacc.2015.02.018. [PubMed:25881932 ]
Chen C, Hou G, Zeng C, Ren Y, Chen X, Peng C: Metabolomic profiling reveals amino acid and carnitine alterations as metabolic signatures in psoriasis. Theranostics. 2021 Jan 1;11(2):754-767. doi: 10.7150/thno.51154. eCollection 2021. [PubMed:33391503 ]
Niziol J, Bonifay V, Ossolinski K, Ossolinski T, Ossolinska A, Sunner J, Beech I, Arendowski A, Ruman T: Metabolomic study of human tissue and urine in clear cell renal carcinoma by LC-HRMS and PLS-DA. Anal Bioanal Chem. 2018 Jun;410(16):3859-3869. doi: 10.1007/s00216-018-1059-x. Epub 2018 Apr 16. [PubMed:29658093 ]
Violante S, Ijlst L, Ruiter J, Koster J, van Lenthe H, Duran M, de Almeida IT, Wanders RJ, Houten SM, Ventura FV: Substrate specificity of human carnitine acetyltransferase: Implications for fatty acid and branched-chain amino acid metabolism. Biochim Biophys Acta. 2013 Jun;1832(6):773-9. doi: 10.1016/j.bbadis.2013.02.012. Epub 2013 Feb 24. [PubMed:23485643 ]
Gunstone, Frank D., John L. Harwood, and Albert J. Dijkstra (2007). The lipid handbook with CD-ROM. CRC Press.

Showing metabocard for 3-Hydroxybutyrylcarnitine (HMDB0013127)

Structure for HMDB0013127 (3-Hydroxybutyrylcarnitine)