Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials
Acylcarnitines are fatty acid metabolites that play important roles in many cellular energy metabolism pathways. They have historically been used as important diagnostic markers for inborn errors of fatty acid oxidation and are being intensively studied as markers of energy metabolism, deficits in m...
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| Published in: | Pharmacological reviews Vol. 74; no. 3; p. 506 |
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| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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United States
01.07.2022
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| ISSN: | 1521-0081, 1521-0081 |
| Online Access: | Get more information |
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| Abstract | Acylcarnitines are fatty acid metabolites that play important roles in many cellular energy metabolism pathways. They have historically been used as important diagnostic markers for inborn errors of fatty acid oxidation and are being intensively studied as markers of energy metabolism, deficits in mitochondrial and peroxisomal
-oxidation activity, insulin resistance, and physical activity. Acylcarnitines are increasingly being identified as important indicators in metabolic studies of many diseases, including metabolic disorders, cardiovascular diseases, diabetes, depression, neurologic disorders, and certain cancers. The US Food and Drug Administration-approved drug L-carnitine, along with short-chain acylcarnitines (acetylcarnitine and propionylcarnitine), is now widely used as a dietary supplement. In light of their growing importance, we have undertaken an extensive review of acylcarnitines and provided a detailed description of their identity, nomenclature, classification, biochemistry, pathophysiology, supplementary use, potential drug targets, and clinical trials. We also summarize these updates in the Human Metabolome Database, which now includes information on the structures, chemical formulae, chemical/spectral properties, descriptions, and pathways for 1240 acylcarnitines. This work lays a solid foundation for identifying, characterizing, and understanding acylcarnitines in human biosamples. We also discuss the emerging opportunities for using acylcarnitines as biomarkers and as dietary interventions or supplements for many wide-ranging indications. The opportunity to identify new drug targets involved in controlling acylcarnitine levels is also discussed. SIGNIFICANCE STATEMENT: This review provides a comprehensive overview of acylcarnitines, including their nomenclature, structure and biochemistry, and use as disease biomarkers and pharmaceutical agents. We present updated information contained in the Human Metabolome Database website as well as substantial mapping of the known biochemical pathways associated with acylcarnitines, thereby providing a strong foundation for further clarification of their physiological roles. |
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| AbstractList | Acylcarnitines are fatty acid metabolites that play important roles in many cellular energy metabolism pathways. They have historically been used as important diagnostic markers for inborn errors of fatty acid oxidation and are being intensively studied as markers of energy metabolism, deficits in mitochondrial and peroxisomal β -oxidation activity, insulin resistance, and physical activity. Acylcarnitines are increasingly being identified as important indicators in metabolic studies of many diseases, including metabolic disorders, cardiovascular diseases, diabetes, depression, neurologic disorders, and certain cancers. The US Food and Drug Administration-approved drug L-carnitine, along with short-chain acylcarnitines (acetylcarnitine and propionylcarnitine), is now widely used as a dietary supplement. In light of their growing importance, we have undertaken an extensive review of acylcarnitines and provided a detailed description of their identity, nomenclature, classification, biochemistry, pathophysiology, supplementary use, potential drug targets, and clinical trials. We also summarize these updates in the Human Metabolome Database, which now includes information on the structures, chemical formulae, chemical/spectral properties, descriptions, and pathways for 1240 acylcarnitines. This work lays a solid foundation for identifying, characterizing, and understanding acylcarnitines in human biosamples. We also discuss the emerging opportunities for using acylcarnitines as biomarkers and as dietary interventions or supplements for many wide-ranging indications. The opportunity to identify new drug targets involved in controlling acylcarnitine levels is also discussed. SIGNIFICANCE STATEMENT: This review provides a comprehensive overview of acylcarnitines, including their nomenclature, structure and biochemistry, and use as disease biomarkers and pharmaceutical agents. We present updated information contained in the Human Metabolome Database website as well as substantial mapping of the known biochemical pathways associated with acylcarnitines, thereby providing a strong foundation for further clarification of their physiological roles.Acylcarnitines are fatty acid metabolites that play important roles in many cellular energy metabolism pathways. They have historically been used as important diagnostic markers for inborn errors of fatty acid oxidation and are being intensively studied as markers of energy metabolism, deficits in mitochondrial and peroxisomal β -oxidation activity, insulin resistance, and physical activity. Acylcarnitines are increasingly being identified as important indicators in metabolic studies of many diseases, including metabolic disorders, cardiovascular diseases, diabetes, depression, neurologic disorders, and certain cancers. The US Food and Drug Administration-approved drug L-carnitine, along with short-chain acylcarnitines (acetylcarnitine and propionylcarnitine), is now widely used as a dietary supplement. In light of their growing importance, we have undertaken an extensive review of acylcarnitines and provided a detailed description of their identity, nomenclature, classification, biochemistry, pathophysiology, supplementary use, potential drug targets, and clinical trials. We also summarize these updates in the Human Metabolome Database, which now includes information on the structures, chemical formulae, chemical/spectral properties, descriptions, and pathways for 1240 acylcarnitines. This work lays a solid foundation for identifying, characterizing, and understanding acylcarnitines in human biosamples. We also discuss the emerging opportunities for using acylcarnitines as biomarkers and as dietary interventions or supplements for many wide-ranging indications. The opportunity to identify new drug targets involved in controlling acylcarnitine levels is also discussed. SIGNIFICANCE STATEMENT: This review provides a comprehensive overview of acylcarnitines, including their nomenclature, structure and biochemistry, and use as disease biomarkers and pharmaceutical agents. We present updated information contained in the Human Metabolome Database website as well as substantial mapping of the known biochemical pathways associated with acylcarnitines, thereby providing a strong foundation for further clarification of their physiological roles. Acylcarnitines are fatty acid metabolites that play important roles in many cellular energy metabolism pathways. They have historically been used as important diagnostic markers for inborn errors of fatty acid oxidation and are being intensively studied as markers of energy metabolism, deficits in mitochondrial and peroxisomal -oxidation activity, insulin resistance, and physical activity. Acylcarnitines are increasingly being identified as important indicators in metabolic studies of many diseases, including metabolic disorders, cardiovascular diseases, diabetes, depression, neurologic disorders, and certain cancers. The US Food and Drug Administration-approved drug L-carnitine, along with short-chain acylcarnitines (acetylcarnitine and propionylcarnitine), is now widely used as a dietary supplement. In light of their growing importance, we have undertaken an extensive review of acylcarnitines and provided a detailed description of their identity, nomenclature, classification, biochemistry, pathophysiology, supplementary use, potential drug targets, and clinical trials. We also summarize these updates in the Human Metabolome Database, which now includes information on the structures, chemical formulae, chemical/spectral properties, descriptions, and pathways for 1240 acylcarnitines. This work lays a solid foundation for identifying, characterizing, and understanding acylcarnitines in human biosamples. We also discuss the emerging opportunities for using acylcarnitines as biomarkers and as dietary interventions or supplements for many wide-ranging indications. The opportunity to identify new drug targets involved in controlling acylcarnitine levels is also discussed. SIGNIFICANCE STATEMENT: This review provides a comprehensive overview of acylcarnitines, including their nomenclature, structure and biochemistry, and use as disease biomarkers and pharmaceutical agents. We present updated information contained in the Human Metabolome Database website as well as substantial mapping of the known biochemical pathways associated with acylcarnitines, thereby providing a strong foundation for further clarification of their physiological roles. |
| Author | Makrecka-Kuka, Marina Kuka, Janis Liepinsh, Edgars Guo, An Chi Schiöth, Helgi B Oler, Eponine Smesny, Stefan Sen, Zumrut Duygu Zheng, Jiamin Wishart, David S Vilskersts, Reinis Attwood, Misty M Nordberg, Didi Tian, Siyang Dambrova, Maija |
| Author_xml | – sequence: 1 givenname: Maija surname: Dambrova fullname: Dambrova, Maija email: helgis@bmc.uu.se, maija.dambrova@farm.osi.lv organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) helgis@bmc.uu.se maija.dambrova@farm.osi.lv – sequence: 2 givenname: Marina surname: Makrecka-Kuka fullname: Makrecka-Kuka, Marina organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 3 givenname: Janis surname: Kuka fullname: Kuka, Janis organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 4 givenname: Reinis surname: Vilskersts fullname: Vilskersts, Reinis organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 5 givenname: Didi surname: Nordberg fullname: Nordberg, Didi organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 6 givenname: Misty M surname: Attwood fullname: Attwood, Misty M organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 7 givenname: Stefan surname: Smesny fullname: Smesny, Stefan organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 8 givenname: Zumrut Duygu surname: Sen fullname: Sen, Zumrut Duygu organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 9 givenname: An Chi surname: Guo fullname: Guo, An Chi organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 10 givenname: Eponine surname: Oler fullname: Oler, Eponine organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 11 givenname: Siyang surname: Tian fullname: Tian, Siyang organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 12 givenname: Jiamin surname: Zheng fullname: Zheng, Jiamin organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 13 givenname: David S surname: Wishart fullname: Wishart, David S organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 14 givenname: Edgars surname: Liepinsh fullname: Liepinsh, Edgars organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) – sequence: 15 givenname: Helgi B surname: Schiöth fullname: Schiöth, Helgi B email: helgis@bmc.uu.se, maija.dambrova@farm.osi.lv organization: Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia (M.D., M.M.-K., J.K., R.V., E.L.); Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden, (D.N., M.M.A., H.B.S.); Department of Psychiatry, Jena University Hospital, Jena, Germany (S.S., Z.D.S.); and Department of Biological Sciences, University of Alberta, Edmonton, Canada (A.C.G., E.O., S.T., J.Z., D.S.W.) helgis@bmc.uu.se maija.dambrova@farm.osi.lv |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35710135$$D View this record in MEDLINE/PubMed |
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