Pathogenesis of methionine-induced toxicity☆

TLDR: In support of the concept that the biochemical changes induced by methionine intoxication are mediated through an hepatic ATP insufficiency is the finding that adenine, administered to intoxicated animals completely reverses the hypoglycemic effects of methionines.

Abstract: L-methionine 10 mMole/Kg. per day administered orally to guinea pigs leads to a state characterized early by fatty liver, hypoglycemia and aminoacidemia and later by hypothermia, profound hypoglycemia and death within 60 hours. Paralleling the development of this state is a progressive fall in hepatic ATP probably caused by binding of available hepatic ATP to methionine, thus forming increasing and substantial amounts of hepatocellular S-adenosylmethionine and S-adenosylhomocysteine. In support of the concept that the biochemical changes induced by methionine intoxication are mediated through an hepatic ATP insufficiency is the finding that adenine, administered to intoxicated animals completely reverses the hypoglycemic effects of methionine. The possibility that a similar mechanism of intoxication occurs in human methionine ingestion and hypermethioninemic states is discussed.