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.)
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.).
Pharmacol Rev. 2022 Jul;74(3):506-551. doi: 10.1124/pharmrev.121.000408.
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.
酰基肉碱是脂肪酸代谢物，在许多细胞能量代谢途径中发挥重要作用。它们历史上一直被用作脂肪酸氧化先天性错误的重要诊断标志物，并且正在作为能量代谢、线粒体和过氧化物酶体β氧化活性、胰岛素抵抗和身体活动的标志物进行深入研究。酰基肉碱正越来越多地被确定为许多疾病代谢研究的重要指标，包括代谢紊乱、心血管疾病、糖尿病、抑郁症、神经障碍和某些癌症。美国食品和药物管理局批准的药物左旋肉碱以及短链酰基肉碱（乙酰肉碱和丙酰肉碱）现在被广泛用作膳食补充剂。鉴于它们的重要性日益增加，我们对酰基肉碱进行了广泛的回顾，并详细描述了它们的身份、命名、分类、生物化学、病理生理学、补充用途、潜在的药物靶点和临床试验。我们还在人类代谢组数据库中总结了这些更新，其中包括 1240 种酰基肉碱的结构、化学式、化学/光谱特性、描述和途径的信息。这项工作为在人类生物样本中识别、表征和理解酰基肉碱奠定了坚实的基础。我们还讨论了将酰基肉碱用作生物标志物以及作为许多广泛适应症的饮食干预或补充剂的新机会。还讨论了识别参与控制酰基肉碱水平的新药物靶点的机会。
本综述提供了酰基肉碱的全面概述，包括它们的命名、结构和生物化学以及作为疾病生物标志物和药物制剂的用途。我们介绍了人类代谢组数据库网站中包含的更新信息以及与酰基肉碱相关的已知生化途径的大量映射，从而为进一步阐明其生理作用提供了坚实的基础。
