Glycine-enhanced inhibition of rat liver nucleotide pyrophosphatase/phosphodiesterase-I by EDTA: a full account of the reported inhibition by commercial preparations of acidic fibroblast growth factor (FGF-1)

FEBS Lett. 1998 Jan 2;421(1):77-9. doi: 10.1016/s0014-5793(97)01536-6.

Abstract

The earlier reported inhibition of rat liver nucleotide pyrophosphatase/phosphodiesterase I (EC 3.1.6.9/EC 3.1.4.1; NPP/PDE) by culture-grade acidic fibroblast growth factor (FGF-1) correlates with a low-Mr contaminant. 1H-NMR analyses revealed EDTA in the total-volume fractions of a gel-filtration experiment, where all the inhibitory activity of the FGF-1 preparation was recovered. NPP/PDE inhibition by EDTA (and by unfractionated FGF-1 or the EDTA-containing fractions) was time-dependent, blocked by the substrate p-nitrophenyl-dTMP, and strongly enhanced by glycine. The use of glycine buffers in earlier work was critical to the apparent inhibition by FGF-1. The results point to a conformational change favored by glycine that may be relevant to the biological role of NPP/PDE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Synergism
  • Edetic Acid / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Fibroblast Growth Factor 1 / pharmacology*
  • Glycine / pharmacology*
  • Kinetics
  • Liver / enzymology*
  • Phosphodiesterase I
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / metabolism*
  • Pyrophosphatases / antagonists & inhibitors*
  • Rats

Substances

  • Enzyme Inhibitors
  • Phosphodiesterase Inhibitors
  • Fibroblast Growth Factor 1
  • Edetic Acid
  • Phosphoric Diester Hydrolases
  • Phosphodiesterase I
  • Pyrophosphatases
  • nucleotide pyrophosphatase
  • Glycine