Arginine and lysine product inhibition of bovine adrenomedullary carboxypeptidase H, a prohormone processing enzyme.
Carboxypeptidase H (CPH) is one of the later enzymes in the cascade of proteolytic steps required for the posttranslational processing of peptide hormone precursors, including processing of proenkephalin. In this study, CPH activity in the soluble and membrane fractions of enkephalin-containing bovine chromaffin granules was competitively inhibited by its products arginine and lysine. Ki values for arginine and lysine were 4.6 +/- 1.3 and 7.6 +/- 1.9 mM, respectively, indicating that arginine was a more effective inhibitor than lysine. Other amino acids (at 10 mM) had no effect. The in vivo intragranular concentrations of lysine and arginine are similar to the measured Ki values, indicating that product inhibition of CPH by basic amino acids may occur in vivo.
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Department of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
D000313:Adrenal Medulla / Q000201:enzymology*; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D002837:Chromaffin Granules / Q000201:enzymology; D007700:Kinetics; D008239:Lysine / Q000378:metabolism*; D008969:Molecular Sequence Data; D043484:Proprotein Convertases; D029701:Saccharomyces cerevisiae Proteins; D012697:Serine Endopeptidases; D013381:Subtilisins
D029701:Saccharomyces cerevisiae Proteins; D001120:Arginine; D002268:Carboxypeptidases; D043423:Carboxypeptidase H; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; C058751:KEX2 protein, S cerevisiae; D008239:Lysine