Rat and human fatty acid amide hydrolases: Overt similarities and hidden differences

Almerinda Di Venere, Enrico Dainese, Filomena Fezza, Beatrice Clotilde Angelucci, Nicola Rosato, Benjamin F. Cravatt, Alessandro Finazzi-Agrò, Giampiero Mei, Mauro MacCarrone

Research output: Contribution to journalArticle

Abstract

Fatty acid amide hydrolase (FAAH) is a membrane protein that plays a relevant role in the metabolism of fatty acid amides and esters. It degrades important neurotransmitters such as oleamide and anandamide, and it has been involved in a number of human pathological conditions, representing therefore a valuable target for biochemical and pharmacological research. In this study, we have investigated in vitro the structure-function relationship of rat and human FAAHs. In particular circular dichroism, fluorescence spectroscopy and light scattering measurements have been performed, in order to characterize the structural features of the two proteins, both in the presence and absence of the irreversible inhibitor methoxyarachidonyl-fluorophosphonate. The results demonstrate that the structural dynamics of the two FAAHs are different, despite their high sequence homology and overall similarity in temperature-dependence. Additionally, membrane binding and kinetic assays of both FAAHs indicate that also the functional properties of the two enzymes are different in their interaction with lipid bilayers and with exogenous inhibitors. These findings suggest that pre-clinical studies of FAAH-dependent human diseases based only on animal models should be interpreted with caution, and that the efficacy of new drugs targeted to FAAH should be tested in vitro, on both rat and human enzymes.

Original languageEnglish
Pages (from-to)1425-1433
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1821
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Anandamide hydrolase
  • Endocannabinoid
  • Fluorescence
  • Membrane binding
  • Protein aggregation and stability

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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  • Cite this

    Di Venere, A., Dainese, E., Fezza, F., Angelucci, B. C., Rosato, N., Cravatt, B. F., Finazzi-Agrò, A., Mei, G., & MacCarrone, M. (2012). Rat and human fatty acid amide hydrolases: Overt similarities and hidden differences. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1821(11), 1425-1433. https://doi.org/10.1016/j.bbalip.2012.07.021