Slow reversible inhibitions of rabbit muscle aldolase with substrate analogues: synthesis, enzymatic kinetics and UV difference spectroscopy studies

Bioorg Med Chem. 1996 Dec;4(12):2043-54. doi: 10.1016/s0968-0896(96)00221-0.

Abstract

Various dihydroxyacetone-phosphate (DHAP) analogues bearing an aromatic ring or beta-dicarbonyl structures were synthesized. Their capacity to form a stabilized iminium ion or conjugated enamine in the reaction catalyzed by rabbit muscle aldolase (EC 4.1.2.13) were investigated by enzymatic kinetics and UV difference spectroscopic techniques. Whereas the aromatic derivative led to competitive inhibition without detectable iminium ion formation, slow reversible inhibitions of aldolase by beta-dicarbonyl compounds was shown to have taken place. Conjugated enamine formation at the active site of the enzyme was detected by their specific absorbances close to 317 nm.

MeSH terms

  • Acetophenones / chemical synthesis*
  • Acetophenones / metabolism
  • Acetophenones / pharmacology
  • Aminocaproates / chemistry
  • Aminocaproates / metabolism
  • Animals
  • Binding, Competitive
  • Dihydroxyacetone Phosphate / analogs & derivatives*
  • Dihydroxyacetone Phosphate / chemistry
  • Dihydroxyacetone Phosphate / pharmacology*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Fructose-Bisphosphate Aldolase / antagonists & inhibitors*
  • Kinetics
  • Muscles / enzymology
  • Organophosphates / chemical synthesis*
  • Organophosphates / metabolism
  • Organophosphates / pharmacology
  • Pentanones / chemical synthesis*
  • Pentanones / metabolism
  • Pentanones / pharmacology
  • Rabbits
  • Spectrum Analysis / methods
  • Time Factors
  • Ultraviolet Rays

Substances

  • (2,4-dioxo)butyl phosphate
  • 2-(2-hydroxyphenyl)-2-oxoethyl phosphate
  • Acetophenones
  • Aminocaproates
  • Enzyme Inhibitors
  • Organophosphates
  • Pentanones
  • 1-(phosphonooxy)-2,4-pentanedione
  • Dihydroxyacetone Phosphate
  • Fructose-Bisphosphate Aldolase