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Preparation and In Vivo Use of an Activity-based Probe for N-acylethanolamine Acid Amidase
Published on: November 23, 2016
Human butyrylcholinesterase components differ in aryl acylamidase activity.
María F Montenegro1, T Moral-Naranjo María, María Páez de la Cadena
1Departamento de Bioquímica y Biología Molecular-A, Edificio de Veterinaria, Universidad de Murcia, E-30071 Murcia, Spain.
Biological Chemistry
|January 23, 2008
Summary
Butyrylcholinesterase (BuChE) exhibits aryl acylamidase (AAA) activity. Monomers show higher AAA activity than tetramers, suggesting aggregation affects enzyme function and cellular AAA activity.
Area of Science:
- Biochemistry
- Enzymology
- Molecular Biology
Background:
- Butyrylcholinesterase (BuChE) possesses both esterase and aryl acylamidase (AAA) activities.
- AAA activity involves the hydrolysis of substrates like o-nitroacetanilide (ONA) and its trifluoro-derivative (F-ONA).
- The relative contributions of amidase versus esterase activities can vary based on BuChE source and oligomeric state.
Purpose of the Study:
- To investigate the differences in aryl acylamidase (AAA) activity between BuChE monomers (G1) and tetramers (G4).
- To explore how the source of human BuChE affects the ratio of amidase to esterase activity.
- To understand the structural and functional implications of BuChE aggregation on its AAA activity.
Main Methods:
- Analysis of human BuChE samples from different sources (serum, colon, kidney) depleted of acetylcholinesterase.
- Enzymatic assays measuring the hydrolysis rates of ONA, F-ONA, and butyrylthiocholine.
- Comparison of AAA and esterase activities between BuChE monomers (G1) and tetramers (G4).
Main Results:
- BuChE monomers (G1) from colon and kidney exhibited significantly faster degradation of ONA and F-ONA compared to tetramers (G4).
- The ratio of F-ONA to butyrylthiocholine hydrolysis was similar for serum G1 and G4 forms, indicating source-specific structural differences in the amidase site.
- Variations in amidase/esterase activity ratios are likely due to post-translational modifications, monomer/oligomer proportions, and tetramer degradation capacity.
Conclusions:
- Aggregation state significantly influences BuChE's aryl acylamidase (AAA) activity, with monomers being more active than tetramers.
- Source-specific post-translational modifications and oligomerization influence BuChE's AAA activity profile.
- The higher AAA activity of BuChE monomers supports their role in maintaining cellular AAA activity, which could be diminished by tetramerization.
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