Common-type acylphosphatase: steady-state kinetics and leaving-group dependence

Biochem J. 1997 Oct 1;327 ( Pt 1)(Pt 1):177-84. doi: 10.1042/bj3270177.

Abstract

A number of acyl phosphates differing in the structure of the acyl moiety (as well as in the leaving-group pKa of the acids produced in hydrolysis) have been synthesized. The Km and Vmax values for the bovine common-type acylphosphatase isoenzyme have been measured at 25 degrees C and pH 5.3. The values of kcat differ widely in relation to the different structures of the tested acyl phosphates: linear relationships between log kcat and the leaving group pKa, as well as between log kcat/Km and the leaving-group pKa, were observed. On the other hand, the Km values of the different substrates are very close to each other, suggesting that the phosphate moiety of the substrate is the main chemical group interacting with the enzyme active site in the formation of the enzyme-substrate Michaelis complex. The enzyme does not catalyse transphosphorylation between substrate and concentrated nucleophilic acceptors (glycerol and methanol); nor does it catalyse H218O-inorganic phosphate oxygen exchange. It seems that no phosphoenzyme intermediate is formed in the catalytic pathway. Furthermore, during the enzymic hydrolysis of benzoyl phosphate in the presence of 18O-labelled water, only inorganic phosphate (and not benzoate) incorporates 18O, suggesting that no acyl enzyme is formed transiently. all these findings, as well as the strong dependence of kcat upon the leaving group pK1, suggest that neither a nucleophilic enzyme group nor general acid catalysis are involved in the catalytic pathway. The enzyme is competitively inhibited by Pi, but it is not inhibited by the carboxylate ions produced during substrate hydrolysis, suggesting that the last step of the catalytic process is the release of Pi. The activation energy values for the catalysed and spontaneous hydrolysis of benzoyl phosphate have been determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Anhydride Hydrolases / antagonists & inhibitors
  • Acid Anhydride Hydrolases / chemistry
  • Acid Anhydride Hydrolases / metabolism*
  • Acylphosphatase
  • Animals
  • Benzoates / metabolism
  • Cattle
  • Gas Chromatography-Mass Spectrometry
  • Hydrolysis
  • Isoenzymes / metabolism
  • Kinetics
  • Male
  • Oxygen Isotopes
  • Phosphates / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Testis / enzymology
  • Thermodynamics

Substances

  • Benzoates
  • Isoenzymes
  • Oxygen Isotopes
  • Phosphates
  • benzoyl phosphate
  • Acid Anhydride Hydrolases