Identification of A chain cleavage sites in intact insulin produced by insulin protease and isolated hepatocytes

William C. Duckworth, Frederick G Hamel, Juris J. Liepnieks, Daniel E. Peavy, Michael P. Ryan, Mark A. Hermodson, Bruce H. Frank

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)615-621
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume147
Issue number2
DOIs
StatePublished - Sep 15 1987

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Insulysin
Hepatocytes
Insulin
Tyrosine
Degradation
Enzymes
Glutamine
Metabolism
Leucine
High Pressure Liquid Chromatography
Liver

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Identification of A chain cleavage sites in intact insulin produced by insulin protease and isolated hepatocytes. / Duckworth, William C.; Hamel, Frederick G; Liepnieks, Juris J.; Peavy, Daniel E.; Ryan, Michael P.; Hermodson, Mark A.; Frank, Bruce H.

In: Biochemical and Biophysical Research Communications, Vol. 147, No. 2, 15.09.1987, p. 615-621.

Research output: Contribution to journalArticle

Duckworth, William C. ; Hamel, Frederick G ; Liepnieks, Juris J. ; Peavy, Daniel E. ; Ryan, Michael P. ; Hermodson, Mark A. ; Frank, Bruce H. / Identification of A chain cleavage sites in intact insulin produced by insulin protease and isolated hepatocytes. In: Biochemical and Biophysical Research Communications. 1987 ; Vol. 147, No. 2. pp. 615-621.
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