title: Proteolysis at the secretase and amyloidogenic cleavage sites of the beta-amyloid precursor protein by acetylcholinesterase and butyrylcholinesterase using model peptide substrates.
abstract: 1. It was recently proposed that acetylcholinesterase (AChE), in addition to its esteratic activity, has proteolytic activity such that it may cleave the beta-amyloid precursor (beta-APP) within the beta-amyloid sequence. The purpose of this paper was to examine further whether AChE or butyrylcholinesterase (BuChE) had associated proteinase activity that was involved in the metabolism of beta-APP. 2. The ability of various preparations of AChE and BuChE to hydrolyze two synthetic fragments of beta-APP695 as model substrates containing the normal and aberrant cleavage sites was studied. 3. Digestion of these synthetic substrates with commercial preparations of Electrophorus electricus AChE indicated the presence of a trypsin-like proteolytic activity cleaving each peptide at the carboxy-terminal side of an internal lysine residue. 4. Purification of the trypsin-like proteinase activity by aminobenzamidine affinity chromatography yielded a preparation that was devoid of AChE activity but retained all of the proteinase activity. 5. Amino-terminal sequence analysis of this preparation showed that the first 13 amino acid residues were identical to beta-pancreatic trypsin. 6. These data indicate that the proteinase activity found in these commercial preparations of AChE is due to contamination with trypsin.
authors.affiliation: Division of Pharmacology, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
authors.forename: M
authors.initials: M
authors.lastname: de Serres
authors.forename: D
authors.initials: D
authors.lastname: Sherman
authors.forename: W
authors.initials: W
authors.lastname: Chestnut
authors.forename: B M
authors.initials: BM
authors.lastname: Merrill
authors.forename: O H
authors.initials: OH
authors.lastname: Viveros
authors.forename: E J
authors.initials: EJ
authors.lastname: Diliberto
mesh_terms: D000110:Acetylcholinesterase / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D016477:Artifacts; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002846:Chromatography, Affinity; D004593:Electrophorus; D010450:Endopeptidases / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism*; D016415:Sequence Alignment; D014357:Trypsin / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D014357:Trypsin