Mechanism of hypoglycaemic action of methylenecyclopropylglycine.
The effects of methylenecyclopropylglycine (MCPG), the lower homologue of hypoglycin A, on starved rats are described. Upon oral ingestion of MCPG (43 mg/kg), a 50% decrease in blood glucose compared with controls was observed after 4 h. The plasma concentrations of lactate and non-esterified fatty acids were substantially increased during this period. The activity of general acyl-CoA dehydrogenase from isolated rat liver mitochondria was not significantly changed. By contrast, the activity of 2-methyl-(branched-chain)-acyl-CoA dehydrogenase decreased by over 80%. The enzyme activity of enoyl-CoA hydratase (crotonase) from pig kidneys decreased by 80% on incubation with the hypothetically toxic metabolite of MCPG, methylenecyclopropylformyl-CoA. These results suggest that the inhibition spectrum of MCPG is quite different from that of hypoglycin A and that similar physiological effects might result from inhibition of different enzymes of beta-oxidation, e.g. hypoglycaemia and lacticacidemia. Accumulation of medium-chain acyl-CoA thioesters is probably at the origin of disturbances in pyruvate metabolism.
Melde
K
K
University of Konstanz, Federal Republic of Germany.
Buettner
H
H
Boschert
W
W
Wolf
H P
HP
Ghisla
S
S
D044944:Acyl-CoA Dehydrogenases / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003521:Cyclopropanes / Q000494:pharmacology*; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D003521:Cyclopropanes; D007004:Hypoglycemic Agents; C059830:methylenecyclopropylglycine; D044944:Acyl-CoA Dehydrogenases; D004746:Enoyl-CoA Hydratase; D005998:Glycine