Disease relevance of HYPOGLYCIN

• Pesticide toxicity or hypoglycine A poisoning (Ivory Coast, 1984) [1]?
• 2. Injection of hypoglycin into fasted rats maintained on a standard diet caused severe prostration, hypothermia and a massive dicarboxylic aciduria [Tanaka (1972) J. Biol. Chem. 247, 7465-7478] [2].
• Results showed that, although hypoglycin A induced severe hypoglycemia after intravenous application, there was no significant change in insulin levels [3].
• 4-Pentenoic acid, an analog of hypoglycin which is believed to cause Jamaican vomiting sickness, was administered intraperitoneally to rats in an attempt to produce the features of Reye's syndrome in rats [4].

High impact information on HYPOGLYCIN

• Inhibition of gluconeogenesis by hypoglycin: alternate interpretations [5].
• However, in isolated hepatocytes prepared from hypoglycin-treated rats, the conversion of [14C]fructose into glucose and the recycling of [2-3H,U-14C]glucose were not different from that in control hepatocytes [6].
• When hypoglycin was given to rats fed on a clofibrate-containing diet, the oxidation of decanoylcarnitine, which was incomplete after hypoglycin treatment alone, remained incomplete with uncoupled mitochondria, but became apparently complete with coupled mitochondria [7].
• After hypoglycin administration, hepatic mitochondrial butyryl-CoA dehydrogenase activity was inhibited by more than 90% and, surprisingly, the activity of the peroxisomal enzymes studied was largely preserved [7].
• Mechanisms of the metabolic disturbances caused by hypoglycin and by pent-4-enoic acid. In vitro studies [8].

Chemical compound and disease context of HYPOGLYCIN

• Organic aciduria in rats made resistant to hypoglycin toxicity by pretreatment with clofibrate [2].
• The antagonism of the toxicity of hypoglycin by glycine [9].

Biological context of HYPOGLYCIN

• The maximum tolerated dose (MTD) of hypoglycin A was determined by feeding rats the ackee and control diets over a 30-day period [10].
• The main conclusion from the comparison is that the toxic ackee constitutent, hypoglycin, produces essentially the same metabolic effects in adults as in children [11].
• The biogenesis of dicarboxylic acid in rats given hypoglycin [12].

Anatomical context of HYPOGLYCIN

• Injection of hypoglycin to rats doubles (from 22% to 44%) the volume fraction of mitochondria and decreases (from 1.05% to 0.26%) the volume fraction of peroxisomes in hepatocytes [7].
• Extracts of liver mitochondria from donor rats given hypoglycin, the toxic amino acid from the ackee plant (Blighia sapida) showed drastically reduced levels of acyl-CoA dehydrogenase activity with butyryl-CoA as substrate [13].

Associations of HYPOGLYCIN with other chemical compounds

• 1. In isolated rat liver cells, hypoglycin is a less effective inhibitor of gluconeogenesis than its transamination product, methylenecyclopropylpyruvate (ketohypoglycin) [14].
• Oral administration of hypoglycin (5-6 mg/100 g body wt) to weanling rats produces, in addition to the well-recognized organic aciduria, pronounced iminoacidemia, hyperiminoacidura, and decreased activity of proline and hydroxyproline oxidases [15].

Analytical, diagnostic and therapeutic context of HYPOGLYCIN

• Numerous abnormal metabolites were identified in large amounts in the urine of hypoglycin-treated rats using capillary gas chromatography/mass spectrometry-computer analysis [16].

References