Some biological effects of hypoglycin-A, a compound isolated from the fruit of Blighia sapida, have been investigated. Administration of this compound to animals caused drowsiness progressing to coma, and when large doses were given the animals died. For the rat, the oral and intraperitoneal LD50 values were 98 and 97 mg./kg. respectively. Fasting increased the toxicity considerably. The most outstanding biochemical change produced by hypoglycin-A was a delayed hypoglycaemia, the depth of which was related to the dose. The hypoglycaemia was preceded by exhaustion of liver glycogen. There were also smaller decreases in the glycogen stores of the heart, skeletal muscle and kidney, without any increase in blood pyruvate or lactate. Hypoglycin-A lessened the effect of adrenaline on blood glucose and decreased both glucose tolerance and insulin sensitivity.

No abstract

The hypoglycemic agents hypoglycin A and phenformin lower the ATP levels of slices of rat kidney and liver in vitro. These agents, as well as dinitrophenol, interfere with glucose production by kidney and liver slices in the presence of pyruvate or of various intermediate compounds of glycolysis. There is evidence that the activities of fructose-1,6-diphosphatase and glucose-6-phosphatase may be indirectly affected by these agents.

No abstract

The effects of hypoglycin A on the metabolism of L-leucine-C14, L-alanine-C14, and L-glutamic-acid-C14 by rat liver slices have been investigated. Hypoglycin exerted markedly inhibitory effects on the conversion of leucine-C14 to fatty acid, cholesterol, and CO2. Conversion of alanine-C14 and glutamic acid-C14 to fatty acids was also inhibited by hypoglycin. No effects of hypoglycin on the conversion of C14-amino acids into protein or glycogen were demonstrated.