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 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, neurological disorders and certain cancers. The Food and Drug Administration (FDA)-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. Moreover, we also summarize these updates in the Human Metabolome Database (HMDB), 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.