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. 1991 Mar 1;274(Pt 2):395–400. doi: 10.1042/bj2740395

Metabolic consequences of methylenecyclopropylglycine poisoning in rats.

K Melde 1, S Jackson 1, K Bartlett 1, H S Sherratt 1, S Ghisla 1
PMCID: PMC1150150  PMID: 2006907

Abstract

We describe the effects of methylenecyclopropylglycine in fasted rats. A 75% decrease in the blood glucose concentration and an increase of lactate and pyruvate were observed 6 h after administration of 100 mg of this amino acid/kg. By contrast with the effects reported for hypoglycin [Williamson & Wilson (1965) Biochem. J. 94, 19c-21c], the plasma concentrations of ketone bodies decreased after administration of methylenecyclopropylglycine and the concentrations of branched-chain amino acids in the plasma were increased 6-fold. The oxidation of decanoylcarnitine or of palmitate was nearly completely inhibited in rat liver mitochondria from methylenecyclopropylglycine-poisoned rats. The activities of acetoacetyl-CoA and of 3-oxoacyl-CoA thiolase were decreased to 25% and less than 10% of the controls. There was a pronounced aciduria, due to the excretion of dicarboxylic acids and of oxidation products of branched-chain amino acids. The accumulation of the toxic metabolite methylenecyclopropylformyl-CoA in the mitochondrial matrix was detected after administration of methylenecyclopropylglycine. Similarly we confirmed experimentally that methylenecyclopropylacetyl-CoA accumulates in mitochondria incubated with methylenecyclopropylpyruvate.

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Selected References

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