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Kinins IV pp 375-380 | Cite as

Functional Significance of the Subunits of Carboxypeptidase N (Kininase I)

  • Randal A. Skidgel
  • Marleen S. Kawahara
  • Tony E. Hugli
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 198A)

Summary

Carboxypeptidase N (kininase I; 280K) was purified to homogeneity from human plasma. The inactive 83K and active 48K subunits were separated by gel filtration after treatment of homogeneous 280K with guanidine. The two subunits differ in amino acid composition and immunological reactivity. The activities of the 280K and 48K enzymes with naturally occurring substrates were compared to determine whehther the 83K subunit affects enzymatic activity of the 48K. At 60 µM concentration, both the 280K and 48K enzymes cleaved (Lys6)-Met5)-enkephalin fastest followed by (Arg6)-(Met5)-enkephalin, anaphylatoxin C3a, (arg6)-(Leu5)-enkephalin, C3a octapeptide1 and bradykinin. The activity ratios (280K/48K) were: (Arg6)-(Leu5)-enkepha1in, 0.9; bradykinin, 1,0; (Lys6)-(Met5)-enkephalin, 1.1; (Arg6)-(Met5)-enkephalin, 1.2; and anaphylatoxin C3a, 1.7. Thus, while most substrates were cleaved at similar rates, assuming 2 active sites per 280K molecule, anaphylatoxin C3a was cleaved significantly faster by 280K than by 48K. The ratio of activity was similar (1.9) when the C-terminal octapeptide of C3a was the substrate. These results indicate that the larger, inactive 83K subunit may increase the efficiency of cleavage of some peptides by 48K.

Keywords

Peptide Hormone Peptide Substrate Plasma Kallikrein High Molecular Weight Kininogen Penultimate Amino Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Randal A. Skidgel
    • 1
  • Marleen S. Kawahara
    • 2
  • Tony E. Hugli
    • 2
  1. 1.Department of PharmacologyUniversity of Texas Health Science CenterDallasUSA
  2. 2.Department of ImmunologyScripps Clinic and Research FoundationLaJollaUSA

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