Predicting L-carnitine potential as LDH-inhibitor through In Silico approach
1 Department of Medicine, Faculty of Medicine, State University of Malang, Jl. Semarang 5, Malang, East Java, ID 65145,
2 Department of Sports Science, Faculty of Sport Science, State University of Malang, Jl. Semarang 5, Malang, East Java, ID 65145.
Research Article
World Journal of Advanced Research and Reviews, 2024, 21(02), 481–486
Article DOI: 10.30574/wjarr.2024.21.2.0446
Publication history:
Received on 25 December 2023; revised on 03 February 2024; accepted on 06 February 2024
Abstract:
Background: L-carnitine (LC) is suggested to inhibit lactate accumulation post-exercise. However, the exact mechanism of how LC inhibits lactate accumulation is still elusive. Lactate dehydrogenase (LDH) is a key enzyme that catalyzes the interconversion of pyruvate and lactate. Thus, the present study aimed to investigate the effect of LC in inhibiting LDH through in silico approach.
Methods: The methods used in this study consisted of protein and ligand data collection, pharmacokinetic analysis, molecular docking, and molecular dynamics. The ligands used in this study are L-Carnitine and LDH-A inhibitor (AZ-33) as the control ligand, while the protein is human muscle LDH-A.
Results: The results of this study indicate that L-carnitine has the potential to be an oral-drug candidate as it fulfills all Lipinski criteria and shows good cell membrane permeability. However, molecular docking showed that LC has weaker binding affinity values (-5.2 kcal/mol) than AZ-33 (-8.8 kcal/mol) to LDH-A. LC also interacts with different amino acid residues in LDH-A compared to AZ-33. Despite that, the molecular dynamic study revealed that LC forms more stable interactions with LDH-A.
Conclusion: LC can bind to LDH-A with more stability than AZ-33, despite its weaker binding affinity to LDH-A and different interacting residues. Further study is needed to investigate the other mechanism that explains the effect of LC in inhibiting lactate accumulation.
Keywords:
Carnitine; Lactate Dehydrogenase; In Silico; Molecular Docking
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