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Citral Inhibition of Human Salivary Aldehyde Dehydrogenase

Cell Biochemistry and Biophysics volume 78, pages 31–42 (2020)Cite this article

Abstract

Human salivary aldehyde dehydrogenase (hsALDH) protects us from the toxic effect of aldehydes. It has both diagnostic and therapeutic importance. Citral possesses many biological and pharmacological properties. The aim of this work was to investigate the inhibitory effect and the mechanism of inhibition of citral on hsALDH. Citral inhibits the dehydrogenase activity of hsALDH. It decreased the substrate affinity and to a lesser extent, the catalytic efficiency of hsALDH. Citral showed linear mixed-type inhibition with a higher tendency of competitive behavior with little, but significant, non-competitive inhibition. The nucleophilicity of active site Cys residue is not a significant contributing factor in the inhibition process. Citral shows uncompetitive inhibition towards the co-enzyme (NAD+). α-helix and β-sheet content of the enzyme were changed in presence of citral. Biophysical studies showed that citral quenches the intrinsic fluorescence of hsALDH in a static manner by forming complex with the enzyme. Molecular docking study showed that both the isomers of citral bind to the catalytic site of hsALDH interacting with few evolutionary preserved amino acid residues through multiple non-covalent interactions. Ligand efficiency metrics values indicate that citral is an efficient ligand for the enzyme in terms of its physicochemical and pharmacokinetic properties.

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Acknowledgements

Facilities provided by the Aligarh Muslim University are gratefully acknowledged. A.A.L. was a Senior Research Fellow of Department of Biotechnology, Government of India.

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This work did not receive any specific research fund.

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Affiliations

  1. Enzymology Laboratory, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India

    Amaj Ahmed Laskar, Sumbul Ahmad, Amiruddin Hashmi & Hina Younus

  2. Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, 51452, Saudi Arabia

    Masood Alam Khan

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  1. Amaj Ahmed Laskar
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  2. Masood Alam Khan
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Correspondence to Hina Younus.

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The collection and use of human saliva samples was approved by the Bioethical Committee of the Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.

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Laskar, A.A., Khan, M.A., Ahmad, S. et al. Citral Inhibition of Human Salivary Aldehyde Dehydrogenase. Cell Biochem Biophys 78, 31–42 (2020). https://doi.org/10.1007/s12013-019-00891-4

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  • DOI: https://doi.org/10.1007/s12013-019-00891-4

Keywords

  • Salivary ALDH
  • Citral
  • Enzyme kinetics
  • Aldehyde toxicity
  • Oral carcinogenesis