Metabolic effects of hypoglycin and methylenecyclopropaneacetic acid

It is suggested that hypoglycin toxicity is due to the formation of methylenecyclopropaneacetate which inhibits the oxidation of fatty acids and decreases respiration and uncouples phosphorylation.

Abstract

The metabolic effects of methylenecyclopropanepyruvate and methylenecyclopropaneacetate have been investigated. Both are formed in rat liver from the toxic compound l-α-amino-β-methylenecyclopropanepropionic acid (hypoglycin) which is present in the fruits of Blighia sapida König. 1. The production of CO2in vivo in hypoglycin-poisoned rats is diminished, mainly due to a reduction in palmitate oxidation. 2. Methylenecyclopropanepyruvate slightly inhibits the decarboxylation of 1-14C pyruvate in mitochondria whereas methylenecyclopropaneacetate does not affect the oxidation of 2-14C pyruvate. 3. Methylenecyclopropaneacetate inhibits in mitochondria the oxidation of C12- to C18-fatty acids but not that of C4- to C10-fatty acids. 4. Oxidative phosphorylation in mitochondria is uncoupled and respiration inhibited by methylenecyclopropaneacetate. No uncoupling effect is observed in submitochondrial digitonin particles. 5. Acetoacetate production from palmitate in mitochondria is inhibited by methylenecyclopropaneacetate at concentrations which do not affect fatty acid oxidation. 6. The incorporation of acetate into cholesterol is inhibited, whereas that of mevalonate is unimpaired in the presence of methylenecyclopropaneacetate. 7. It is suggested that hypoglycin toxicity is due to the formation of methylenecyclopropaneacetate which inhibits the oxidation of fatty acids. Their accumulation decreases respiration and uncouples phosphorylation.