title: Degradation of proinsulin C-peptide in kidney and placenta extracts by a specific endoprotease activity.
abstract: Degradation of proinsulin C-peptide in mouse kidney and human placenta extracts was studied using reverse-phase high-performance liquid chromatography and nano-electrospray mass spectrometry. In total, 15 proteolytic cleavage sites were identified in human and mouse C-peptides. Early sites included the peptide bonds N-terminal of Val/Leu10, Leu12, Leu21, Leu24 and Leu26 in different combinations for the two tissues and two peptides. Notably, these cleavages were N-terminal of a hydrophobic residue, and all but one N-terminal of Leu. A late degradation product of the human peptide detected in the kidney extract was the C-terminal hexapeptide, containing just one residue more than the biologically active C-terminal pentapeptide of C-peptide. We conclude that the degradation of C-peptide in kidney and placenta follows similar patterns, dominated by endopeptidase cleavages N-terminal of Leu.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Melles
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
authors.forename: S
authors.initials: S
authors.lastname: Tryggvason
authors.forename: K Gemzell
authors.initials: KG
authors.lastname: Danielsson
authors.forename: K
authors.initials: K
authors.lastname: Ekberg
authors.forename: K
authors.initials: K
authors.lastname: Tryggvason
authors.forename: J
authors.initials: J
authors.lastname: Wahren
authors.forename: T
authors.initials: T
authors.lastname: Bergman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002096:C-Peptide / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D010450:Endopeptidases / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007930:Leucine / Q000737:chemistry; D013058:Mass Spectrometry; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010920:Placenta / Q000378:metabolism*; D011384:Proinsulin / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
chemical_list: D002096:C-Peptide; D010455:Peptides; D011384:Proinsulin; D010450:Endopeptidases; D007930:Leucine