Butyrylcholinesterase in metabolic syndrome

Gumpeny R. Sridhar, Allam Appa Rao, Kudipudi Srinivas, Gumpeny Nirmala, Gumpeny Lakshmi, Dasika Suryanarayna, Padmanabhuni V. Nageswara Rao, Dowluru G.S.V.G.L. Kaladhar, Sali Veeresh Kumar, Tatavarthi Uma Devi, Turaga Nitesh, Thota Hanuman

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Abstract

Butyrylcholinesterase may have a role in a number of metabolic functions and could affect the expression of insulin resistance syndrome. We present our integrated work using clinical, biochemical and bioinformatic approaches to delineate the possible function of this enzyme. Initially, we constructed a phylogenic tree with nucleotides and amino acid sequences and showed the existence of similar sequences in bacteria, plants and in other animals. We also demonstrated a possible pathogenic role for BChE in the common existence of insulin resistance, type 2 diabetes and Alzheimer's disease by in silico method and followed it up with a diabetic mouse study where cognition was slowed along with changes in BChE levels. In the next group of in silico studies, we employed THEMATICS method to identify the amino acids at the active site and later performed docking studies with drugs. THEMATICS predicted two clusters of ionisable amino acid residues that are in proximity: one with two residues and another with 11 showed perturbation in the THEMATICS curves. Using ISIS/Draw 2.5SP4, ARGUSLAB 4.0.1 and HEX 5.1. software. 3-D ligands were docked with BChE motif (from PDB). We did not find any of the ligands studied with significant docking distance, indicating they did not have direct interaction with the active site. Subsequently we performed in silico studies to compare the secondary structure and domain of BChE. Protein-protein interaction showed the following intersections with BChE UBE21, CHAT, APOE, AATF, DF ALDH9A1, PDHX, PONI PSME3 and ATP6VOA2. The integrative physiological roles of proteins with poorly known functions can be approached by generating leads in silico, which can be studied in vivo, setting into movement an iterative process.

Original languageEnglish
Pages (from-to)648-651
Number of pages4
JournalMedical Hypotheses
Volume75
Issue number6
DOIs
Publication statusPublished - 01-12-2010
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Sridhar, G. R., Rao, A. A., Srinivas, K., Nirmala, G., Lakshmi, G., Suryanarayna, D., Nageswara Rao, P. V., Kaladhar, D. G. S. V. G. L., Kumar, S. V., Devi, T. U., Nitesh, T., & Hanuman, T. (2010). Butyrylcholinesterase in metabolic syndrome. Medical Hypotheses, 75(6), 648-651. https://doi.org/10.1016/j.mehy.2010.08.008