| Record Information |
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| Version | 4.0 |
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| Status | Detected and Quantified |
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| Creation Date | 2005-11-16 15:48:42 UTC |
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| Update Date | 2021-04-12 19:31:18 UTC |
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| HMDB ID | HMDB0000552 |
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| Secondary Accession Numbers | |
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| Metabolite Identification |
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| Common Name | 3-Methylglutarylcarnitine |
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| Description | 3-Methylglutarylcarnitine is an acylcarnitine. More specifically, it is an methylglutaric 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-Methylglutarylcarnitine is therefore classified as a medium chain AC. As a medium-chain acylcarnitine 3-methylglutarylcarnitine is somewhat less abundant than short-chain acylcarnitines. These are formed either through esterification with L-carnitine or through the peroxisomal metabolism of longer chain acylcarnitines (PMID: 30540494 ). Many medium-chain acylcarnitines can serve as useful markers for inherited disorders of fatty acid metabolism. In particular 3-methylglutarylcarnitine is elevated in the blood or plasma of individuals with psoriasis (PMID: 33391503 ), CVD (PMID: 32376321 ), Norman-Roberts syndrome (PMID: 15083694 ), type 2 diabetes Mellitus (PMID: 20111019 , PMID: 19369366 , PMID: 29436377 ), carnitine palmitoyl-trasferase 2 deficiency (PMID: 9657346 ), Familial Mediterranean Fever (PMID: 29900937 ), multiple acyl coenzyme A dehydrogenase Deficiency (PMID: 30510944 ), CVD in type 2 diabetes Mellitus (PMID: 32431666 ), and gestational diabetes mellitus (PMID: 29436377 ). It is also decreased in the blood or plasma of individuals with Celiac disease (PMID: 16425363 ). 3-Methylglutarylcarnitine is elevated in the urine of individuals with medium-chain acyl-CoA dehydrogenase deficiency (PMID: 1635814 , PMID: 2246856 ). 3-Methylglutarylcarnitine is a diagnostic metabolite of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. It is also identified in the urine of patients with Reye-like syndrome (PMID: 3958190 , 10927963 ). Carnitine octanoyltransferase (CrOT, EC:2.3.1.137) is responsible for the synthesis of all medium-chain (MCAC, C5-C12) and medium-length branched-chain acylcarnitines in peroxisomes (PMID: 10486279 ). 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]. |
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| Structure | |
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| Synonyms | | Value | Source |
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| (3R)-3-{[(3R)-4-carboxy-3-methylbutanoyl]oxy}-4-(trimethylazaniumyl)butanoic acid | Generator | | 3-Methylglutarylcarnitine | HMDB | | Methylglutarylcarnitine | HMDB | | O-3-Methylglutarylcarnitine | HMDB |
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| Chemical Formula | C13H23NO6 |
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| Average Molecular Weight | 289.328 |
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| Monoisotopic Molecular Weight | 289.152537465 |
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| IUPAC Name | (3R)-3-{[(3R)-4-carboxy-3-methylbutanoyl]oxy}-4-(trimethylazaniumyl)butanoate |
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| Traditional Name | (3R)-3-{[(3R)-4-carboxy-3-methylbutanoyl]oxy}-4-(trimethylammonio)butanoate |
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| CAS Registry Number | 102673-95-0 |
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| SMILES | C[C@H](CC(O)=O)CC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C |
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| InChI Identifier | InChI=1S/C13H23NO6/c1-9(5-11(15)16)6-13(19)20-10(7-12(17)18)8-14(2,3)4/h9-10H,5-8H2,1-4H3,(H-,15,16,17,18)/t9-,10-/m1/s1 |
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| InChI Key | HFCPFJNSBPQJDP-NXEZZACHSA-N |
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| Chemical Taxonomy |
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| 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. |
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| Kingdom | Organic compounds |
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| Super Class | Lipids and lipid-like molecules |
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| Class | Fatty Acyls |
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| Sub Class | Fatty acid esters |
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| Direct Parent | Acyl carnitines |
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| Alternative Parents | |
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| Substituents | - Acyl-carnitine
- Tricarboxylic acid or derivatives
- Tetraalkylammonium salt
- Quaternary ammonium salt
- 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
- Organooxygen compound
- Organonitrogen compound
- Carbonyl group
- Amine
- Aliphatic acyclic compound
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| Molecular Framework | Aliphatic acyclic compounds |
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| External Descriptors | Not Available |
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| Ontology |
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| Disposition | Route of exposure: Source: Biological location: |
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| Process | Naturally occurring process: |
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| Role | Industrial application: Biological role: |
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| Physical Properties |
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| State | Solid |
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| Experimental Properties | | Property | Value | Reference |
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| Melting Point | Not Available | Not Available | | Boiling Point | Not Available | Not Available | | Water Solubility | Not Available | Not Available | | LogP | Not Available | Not Available |
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| Predicted Properties | |
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| General References | - Roe CR, Millington DS, Maltby DA: Identification of 3-methylglutarylcarnitine. A new diagnostic metabolite of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. J Clin Invest. 1986 Apr;77(4):1391-4. [PubMed:3958190 ]
- Lee C, Tsai FJ, Wu JY, Peng CT, Tsai CH, Hwu WL, Wang TR, Millington DS: 3-hydroxy-3-methylglutaric aciduria presenting with Reye like syndrome: report of one case. Acta Paediatr Taiwan. 1999 Nov-Dec;40(6):445-7. [PubMed:10927963 ]
- Jooste S, Erasmus E, Mienie LJ, de Wet WJ, Gibson KM: The detection of 3-methylglutarylcarnitine and a new dicarboxylic conjugate, 3-methylglutaconylcarnitine, in 3-methylglutaconic aciduria. Clin Chim Acta. 1994 Oct 14;230(1):1-8. [PubMed:7850987 ]
- 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 ]
- Violante S, Achetib N, van Roermund CWT, Hagen J, Dodatko T, Vaz FM, Waterham HR, Chen H, Baes M, Yu C, Argmann CA, Houten SM: Peroxisomes can oxidize medium- and long-chain fatty acids through a pathway involving ABCD3 and HSD17B4. FASEB J. 2019 Mar;33(3):4355-4364. doi: 10.1096/fj.201801498R. Epub 2018 Dec 12. [PubMed:30540494 ]
- 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 ]
- Kukharenko A, Brito A, Kozhevnikova MV, Moskaleva N, Markin PA, Bochkareva N, Korobkova EO, Belenkov YN, Privalova EV, Larcova EV, Ariani A, La Frano MR, Appolonova SA: Relationship between the plasma acylcarnitine profile and cardiometabolic risk factors in adults diagnosed with cardiovascular diseases. Clin Chim Acta. 2020 Aug;507:250-256. doi: 10.1016/j.cca.2020.04.035. Epub 2020 May 4. [PubMed:32376321 ]
- Caksen H, Tuncer O, Kirimi E, Fryns JP, Uner A, Unal O, Cinal A, Odabas D: Report of two Turkish infants with Norman-Roberts syndrome. Genet Couns. 2004;15(1):9-17. [PubMed:15083694 ]
- Mihalik SJ, Goodpaster BH, Kelley DE, Chace DH, Vockley J, Toledo FG, DeLany JP: Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity (Silver Spring). 2010 Sep;18(9):1695-700. doi: 10.1038/oby.2009.510. Epub 2010 Jan 28. [PubMed:20111019 ]
- Adams SH, Hoppel CL, Lok KH, Zhao L, Wong SW, Minkler PE, Hwang DH, Newman JW, Garvey WT: Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid beta-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women. J Nutr. 2009 Jun;139(6):1073-81. doi: 10.3945/jn.108.103754. Epub 2009 Apr 15. [PubMed:19369366 ]
- Batchuluun B, Al Rijjal D, Prentice KJ, Eversley JA, Burdett E, Mohan H, Bhattacharjee A, Gunderson EP, Liu Y, Wheeler MB: Elevated Medium-Chain Acylcarnitines Are Associated With Gestational Diabetes Mellitus and Early Progression to Type 2 Diabetes and Induce Pancreatic beta-Cell Dysfunction. Diabetes. 2018 May;67(5):885-897. doi: 10.2337/db17-1150. Epub 2018 Feb 7. [PubMed:29436377 ]
- Fontaine M, Briand G, Largilliere C, Degand P, Divry P, Vianey-Saban C, Mousson B, Vamecq J: Metabolic studies in a patient with severe carnitine palmitoyltransferase type II deficiency. Clin Chim Acta. 1998 May 25;273(2):161-70. [PubMed:9657346 ]
- Kiykim E, Aktuglu Zeybek AC, Barut K, Zubarioglu T, Cansever MS, Alsancak S, Kasapcopur O: Screening of Free Carnitine and Acylcarnitine Status in Children With Familial Mediterranean Fever. Arch Rheumatol. 2016 Mar 10;31(2):133-138. doi: 10.5606/ArchRheumatol.2016.5696. eCollection 2016 Jun. [PubMed:29900937 ]
- Saral NY, Aksungar FB, Aktuglu-Zeybek C, Coskun J, Demirelce O, Serteser M: Glutaric acidemia type II patient with thalassemia minor and novel electron transfer flavoprotein-A gene mutations: A case report and review of literature. World J Clin Cases. 2018 Nov 26;6(14):786-790. doi: 10.12998/wjcc.v6.i14.786. [PubMed:30510944 ]
- Zhao S, Feng XF, Huang T, Luo HH, Chen JX, Zeng J, Gu M, Li J, Sun XY, Sun D, Yang X, Fang ZZ, Cao YF: The Association Between Acylcarnitine Metabolites and Cardiovascular Disease in Chinese Patients With Type 2 Diabetes Mellitus. Front Endocrinol (Lausanne). 2020 May 5;11:212. doi: 10.3389/fendo.2020.00212. eCollection 2020. [PubMed:32431666 ]
- Bene J, Komlosi K, Gasztonyi B, Juhasz M, Tulassay Z, Melegh B: Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet. World J Gastroenterol. 2005 Nov 14;11(42):6671-5. [PubMed:16425363 ]
- Schmidt-Sommerfeld E, Penn D, Rinaldo P, Kossak D, Li BU, Huang ZH, Gage DA: Urinary medium-chain acylcarnitines in medium-chain acyl-CoA dehydrogenase deficiency, medium-chain triglyceride feeding and valproic acid therapy: sensitivity and specificity of the radioisotopic exchange/high performance liquid chromatography method. Pediatr Res. 1992 Jun;31(6):545-51. [PubMed:1635814 ]
- Bennett MJ, Coates PM, Hale DE, Millington DS, Pollitt RJ, Rinaldo P, Roe CR, Tanaka K: Analysis of abnormal urinary metabolites in the newborn period in medium-chain acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis. 1990;13(5):707-15. [PubMed:2246856 ]
- Ferdinandusse S, Mulders J, IJlst L, Denis S, Dacremont G, Waterham HR, Wanders RJ: Molecular cloning and expression of human carnitine octanoyltransferase: evidence for its role in the peroxisomal beta-oxidation of branched-chain fatty acids. Biochem Biophys Res Commun. 1999 Sep 16;263(1):213-8. [PubMed:10486279 ]
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