n-Octyl gallate as inhibitor of pyruvate carboxylation and lactate gluconeogenesis

J Biochem Mol Toxicol. 2015 Apr;29(4):157-64. doi: 10.1002/jbt.21680. Epub 2014 Dec 8.

Abstract

The alkyl gallates are found in several natural and industrial products. In the latter products, these compounds are added mainly for preventing oxidation. In the present work, the potencies of methyl gallate, n-propyl gallate, n-pentyl gallate, and n-octyl gallate as inhibitors of pyruvate carboxylation and lactate gluconeogenesis were evaluated. Experiments were done with isolated mitochondria and the isolated perfused rat liver. The potency of the gallic acid esters as inhibitors of pyruvate carboxylation in isolated mitochondria obeyed the following decreasing sequence: n-octyl gallate > n-pentyl gallate > n-propyl gallate > methyl gallate. A similar sequence of decreasing potency for lactate gluconeogenesis inhibition in the perfused liver was found in terms of the portal venous concentration. Both actions correlate with the lipophilicity of the compounds. The effects are harmful at high concentrations. At appropriate concentrations, however, octyl gallate should act therapeutically because its inhibitory action on gluconeogenesis will contribute further to its proposed antihyperglycemic effects.

Keywords: alkyl gallates; gluconeogenesis; oxygen uptake; pyruvate carboxylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Gluconeogenesis / drug effects*
  • Lactates / metabolism*
  • Liver / drug effects*
  • Male
  • Mitochondria, Liver / drug effects
  • Pyruvate Carboxylase / antagonists & inhibitors
  • Pyruvates / metabolism*
  • Rats

Substances

  • Lactates
  • Pyruvates
  • octyl gallate
  • Gallic Acid
  • Pyruvate Carboxylase