Kinetic-controlled hydrolysis of Leu-Val-Val-hemorphin-7 catalyzed by angiotensin-converting enzyme from rat brain

Peptides. 2003 Jul;24(7):1075-82. doi: 10.1016/s0196-9781(03)00178-5.

Abstract

Leu-Val-Val-hemorphin-7 (LVV-H7, LVVYPWTQRY), an opioid peptide, was found to be hydrolyzed sequentially by rat brain angiotensin-converting enzyme (ACE) in three steps through dipeptidyl carboxypeptidase activity. The kinetic constants evaluated were in order of: k(1) (0.19 min(-1))>>k(2) (0.0008 min(-1)) approximately k(3) (0.0006 min(-1)) in 10 mM NaCl at pH 7.5 giving rise to LVV-H5 almost quantitatively. The decapeptide was noted to be hydrolyzed 164- and 346-fold more efficiently than angiotensin I (Ang I) in k(cat) and kcat/Km values, respectively, at their optimal conditions. The kinetic-controlled preferential action of the brain enzyme on LVV-H7 is suggestive of its multiple roles in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Angiotensin I / metabolism
  • Animals
  • Brain / enzymology*
  • Catalysis
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Endopeptidases / metabolism
  • Enzyme Activation
  • Gas Chromatography-Mass Spectrometry
  • Hemoglobins / chemical synthesis
  • Hemoglobins / chemistry
  • Hemoglobins / metabolism*
  • Hydrogen-Ion Concentration
  • Hydrolysis / drug effects
  • Kinetics
  • Male
  • Molecular Weight
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Peptidyl-Dipeptidase A / metabolism*
  • Rats
  • Sequence Analysis, Protein
  • Sodium Chloride / pharmacology
  • Spectrometry, Mass, Fast Atom Bombardment
  • Testis / enzymology

Substances

  • Hemoglobins
  • Peptide Fragments
  • Sodium Chloride
  • LVV-hemorphin-7
  • Angiotensin I
  • Endopeptidases
  • dipeptidyl carboxypeptidase
  • Peptidyl-Dipeptidase A