Dambrova 2022 Abstract Bioblast

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Dambrova Maija, Vilskersts R, Liepinsh E(2022) Mitochondrial metabolites acylcarnitines: therapeutic potential and drug targets. Bioblast 2022: BEC Inaugural Conference.

Link: Bioblast 2022: BEC Inaugural Conference

Dambrova Maija, Vilskersts R, Liepinsh Edgars (2022)

Event: Bioblast 2022

Acylcarnitines are esters of L-carnitine that emerge from the energy metabolism pathways of fatty acids in mitochondria and peroxisomes [1]. Depending on the length of the acyl chain, acylcarnitines can be grouped as short-, medium-, long- and very long-chain acylcarnitines. Metabolomic profiling assays that investigate disease and nutrition states often include measurements of different acylcarnitines. This has resulted in increased interest regarding the consequences of elevated/decreased levels of plasma acylcarnitine concentrations and the mechanisms associated with these changes.

Altered acylcarnitine metabolome is characteristic for certain inborn errors of fatty acid metabolism, as well as cardiovascular, metabolic and neurological diseases, and some forms of cancer. Acylcarnitines are considered as biomarkers for such diseases and pathological conditions as insulin resistance, heart failure and fatty acid oxidation metabolism-related inherited diseases. Long-chain acylcarnitines accumulate under conditions of insufficient mitochondrial functionality and can reach tissue levels that can affect enzyme and ion channel activities and impact energy metabolism pathways and cellular homeostasis. These detrimental processes directly impact mitochondrial physiology and can exaggerate arrhythmia, insulin insufficiency, neurodegenerative and neuropsychiatric conditions.

Dietary and pharmacological means can be used to regulate synthesis and transport pathways of acylcarnitines and thus counteract the detrimental effects of their accumulation or reverse deficits. The most abundant acylcarnitines, acetylcarnitine and propionylcarnitine, are used as food supplements to tackle neurological and cardiovascular conditions.

Better understanding of biochemical and molecular mechanisms behind increased/decreased acylcarnitine levels and their physiological and pathological roles forms basis for therapeutic target selection and preclinical drug discovery in future and also explains off-target effects of some clinically used drugs.

Keywords: Acylcarnitine, Mitochondrial energy metabolism, Biomarker, Cardiometabolic diseases Bioblast editor: Plangger M O2k-Network Lab: LV Riga Liepins E


Affiliations

Dambrova M (1,2), Vilskersts R(1,2), Liepinsh E(1)
  1. Latvian Institute of Organic Synthesis, Riga, LV
  2. Riga Stradins University, Riga, LV

References

  1. Dambrova M et al (2022) Acylcarnitines: nomenclature, biomarkers, therapeutic potential, drug targets and clinical trials. Pharmacol Rev 74:1-50.

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