Mode of Action of Hypoglycin and Related Compounds

A Novel mechanism for inhibition of β‐oxidation by methylenecyclopropylacetyl‐CoA, a metabolite of hypoglycin

“…This metabolite is thought to inhibit fatty acid oxidation [6], following administration of hypoglycin to animals, thereby indirectly causing hypoglycaemia [2][3][4]. Here we show that in the presence of methylenecyclopropylacetate (MCPA) fatty acids of chain-lengths greater than Ca are oxidised in isolated mitochondria at a decreased rate and only as far as butyrate.…”

“…Hypoglycin (L-2-amino-3-methylenecyclopropylpropionic acid), the toxic principle of the Jamaican ackee fruit (Blighia sapida) [1][2][3][4], is converted in vivo to methylenecyclopropyl acetyl-CoA (MCPACoA) [5]. This metabolite is thought to inhibit fatty acid oxidation [6], following administration of hypoglycin to animals, thereby indirectly causing hypoglycaemia [2][3][4].…”

Mechanisms of inhibition of fatty acid oxidation by pent-4-enoic acid: evidence against the coenzyme A-depletion hypothesis

“…It was confirmed that 0.1 mM-pent-4-enoic acid causes rapid depletion of free CoA together withan increase ofacid-solubleacyl-CoA and some increase in acetyl-CoAconcentrations (dueto a self-limiting oxidation of pent-4-enoyl-CoA; Sherratt et al, 1971). However, 0.1 mM-cyclopropanecarboxylic acid, which does not inhibit fl-oxidation strongly, caused a similar fall in the CoA concentration and an increase in acid-soluble acyl-CoA concentrations.…”

“…Pent-4-enoic acid strongly inhibits oxidation of fatty acids, pyruvate and 2-oxoglutarate , and these inhibitions depend on the formation of intramitochondrial pent-4-enoyl-CoA (Holland & Sherratt, 1969;Sherratt et al, 1971). Bressler et al (1969) proposed that sequestration of CoA as pent-4-enoyl-CoA and its metabolites impairs CoA-dependent oxidations.…”