The Stereochemistry of Hydrogen Abstraction in Vitamin K-dependent Carboxylation

J Biol Chem. 1984 Dec 25;259(24):15010-2.

Abstract

The stereochemistry of the hydrogen abstraction in the vitamin K-dependent carboxylation of synthetic peptides has been investigated; the carboxylation rates of various peptidic substrates containing a stereospecifically 4-monodeuterated glutamic acid residue have been compared to that of nondeuterated peptides. A significant isotope effect was found only with the substrates containing (4S)-4-deuterated glutamic acid. These data reveal that the rat liver microsomal vitamin K-dependent carboxylase acts stereospecifically in abstracting the 4-pro-S hydrogen of the glutamyl residue. The low values of the measured isotope effects indicate that the hydrogen abstraction does not constitute a limiting step in the carboxylation mechanism.

MeSH terms

  • Animals
  • Carbon Dioxide / metabolism
  • Carbon Radioisotopes
  • Chemical Phenomena
  • Chemistry
  • Deuterium
  • Glutamates / metabolism
  • Glutamic Acid
  • Hydrogen
  • Kinetics
  • Microsomes, Liver / metabolism*
  • Oligopeptides* / metabolism*
  • Rats
  • Structure-Activity Relationship
  • Vitamin K / metabolism*
  • Vitamin K Deficiency / metabolism

Substances

  • Carbon Radioisotopes
  • Glutamates
  • Oligopeptides
  • Vitamin K
  • Carbon Dioxide
  • Glutamic Acid
  • Hydrogen
  • Deuterium