title: Identification of A chain cleavage sites in intact insulin produced by insulin protease and isolated hepatocytes.
abstract: The degradation of insulin by the enzyme insulin protease and by isolated hepatocytes results in proteolytic cleavages in both the A and B chains of intact insulin. Previous studies have shown that one of the A chain cleavages is between A13 leucine and A14 tyrosine and that a second cleavage occurs carboxyl to the A14 residue. In the present study we have used insulin specifically iodinated on the A19 tyrosine and examined the A chain cleavages by the enzyme and by hepatocytes. Insulin degradation products were purified by HPLC and sequenced by automated Edman degradation. Only two A chain cleavage sites were identified, one the previously reported A13-A14 and the other between A14 tyrosine and A15 glutamine. These data thus identify the second A chain cleavage site and further support the role of insulin protease in hepatic metabolism of insulin.
authors.forename: W C
authors.initials: WC
authors.lastname: Duckworth
authors.forename: F G
authors.initials: FG
authors.lastname: Hamel
authors.forename: J J
authors.initials: JJ
authors.lastname: Liepnieks
authors.forename: D E
authors.initials: DE
authors.lastname: Peavy
authors.forename: M P
authors.initials: MP
authors.lastname: Ryan
authors.forename: M A
authors.initials: MA
authors.lastname: Hermodson
authors.forename: B H
authors.initials: BH
authors.lastname: Frank
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism*; D007339:Insulysin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D051381:Rats
chemical_list: D007328:Insulin; D010446:Peptide Fragments; C008147:insulin, iodo-; D010447:Peptide Hydrolases; D007339:Insulysin