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1457. Hypoglycin toxicity caused by a metabolite
NATURAL PRODUCTS
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1457. Hypoglycln toxicity caused by a metabolite von Holt, C., von Holt, M. & Brhm, H. (1966). Metabolic effects of hypo~ycin and
methylenecyclopropaneacetic acid. Biochim. biophys. Acta 125, 11. Hypoglycin (L-~-amino-fl-methylenecyclopropanepropionic acid; I) is thought to be responsible for "vomiting sickness", a disease characterized by vomiting and hypoglycaemia, caused by eating unripe ackee frmt (Cited in F.C.T. 1963, 1, 144). Further work suggested that I exercises ~ts toxic action by blocking fatty acid oxidation (ibid 1963, 1, 145). I is known to be degraded m the hver to methylenecyclopropaneacetlc acid (II) which, according to the present study, appears to be responsible for the toxic effects of I. The reduced production of carbon dioxide (CO2) by rats given I is due mainly to inhibited oxidation of palmitate. Dosage with I is likely to yield intracellular concentrations of II, which has also been shown to inhibit the oxidation of palmitate to COE by isolated rat-liver mitochondria. The effect is restricted to the oxidation of long-chain fatty acids (C12-C18), suggesting, it is argued, that inhibition occurs at the level of the flavin-adenine dinucleotidedependent acyl coenzyme A dehydrogenase reaction. This hypothesis would also explain why riboflavin suppresses the toxicity of I. As well as inhibiting fatty acid oxidation, II inhibits the in vitro mitochondrial production of acetoacetate from palmitate and the incorporation of acetate into cholesterol. It also uncouples oxidative phosphorylation, an effect elicited by dosage with I, and inhibits mitochondrial respiration. It seems reasonable to conclude that II is the toxic metabolite of I. II inhibits fatty acid oxidation, leading to accumulation of long-chain fatty acids inside the mitochondria. This is followed by uncoupling oxidative phosphorylation, causing diminished adenosine triphosphate production, which in turn would contribute to depletion of glycogen stores and subsequent hypoglycaemia. 1458. What causes the plant irritation?
Manno, J. E., Fochtman, F. W., Winek, C. L. & Shanor, S. P. (1967). Toxicity of plants of the genus Dieffenbachia. Toxic. appl. Pharmac. 10, 405. Certain plants of the genus Dieffenbachia produce severe irritation of the oral cavity on ingestion. The irritating factor has not yet been identified, but saponins are not involved and the results reported in this preliminary communication eliminate calcium oxalate (I) crystals and suggest instead that a protein may be implicated. Experiments in rabbits show that the fresh juice of D. picta (1I) is much more irritant than that of D. exotica (III) both to the eye and the buccal cavity. In fact a concentrated suspension of a protein-containing centrifugate of the juice of III had to be used to produce the swelling of the tongue and irritation of the oral cavity characteristically induced by II. It was also found that the eye-irritant properties of I! and III were completely destroyed by storing the fruit juice for 24 hr. No eye irritation was produced by a 0.15 70 suspension of I (the concentration present in the juices) and a much higher concentration (5 70) caused no buccal irritation in rats. Attempts are being made to identify a protein isolated from the juice o f l I I and thought to be the irritant factor. 1459. Steady with the slimming Pittman, F. E. (1966). Primary malabsorption following extreme attempts to lose weight. Gut 7, 154. The malabsorption syndrome, evident in most cases of coeliac disease, is associated with an intolerance of wheat and rye gluten (I) (Cited in F.C.T. 1966, 4, 125). Two most unusual cases are now reported in which this syndrome, with typical symptoms of fatty diarrhoea, multiple nutritional deficiencies and characteristic degenerative changes in the mucosa o f the small intestine, was precipitated in two obese adults by extreme measures
837
1457. Hypoglycln toxicity caused by a metabolite von Holt, C., von Holt, M. & Brhm, H. (1966). Metabolic effects of hypo~ycin and
methylenecyclopropaneacetic acid. Biochim. biophys. Acta 125, 11. Hypoglycin (L-~-amino-fl-methylenecyclopropanepropionic acid; I) is thought to be responsible for "vomiting sickness", a disease characterized by vomiting and hypoglycaemia, caused by eating unripe ackee frmt (Cited in F.C.T. 1963, 1, 144). Further work suggested that I exercises ~ts toxic action by blocking fatty acid oxidation (ibid 1963, 1, 145). I is known to be degraded m the hver to methylenecyclopropaneacetlc acid (II) which, according to the present study, appears to be responsible for the toxic effects of I. The reduced production of carbon dioxide (CO2) by rats given I is due mainly to inhibited oxidation of palmitate. Dosage with I is likely to yield intracellular concentrations of II, which has also been shown to inhibit the oxidation of palmitate to COE by isolated rat-liver mitochondria. The effect is restricted to the oxidation of long-chain fatty acids (C12-C18), suggesting, it is argued, that inhibition occurs at the level of the flavin-adenine dinucleotidedependent acyl coenzyme A dehydrogenase reaction. This hypothesis would also explain why riboflavin suppresses the toxicity of I. As well as inhibiting fatty acid oxidation, II inhibits the in vitro mitochondrial production of acetoacetate from palmitate and the incorporation of acetate into cholesterol. It also uncouples oxidative phosphorylation, an effect elicited by dosage with I, and inhibits mitochondrial respiration. It seems reasonable to conclude that II is the toxic metabolite of I. II inhibits fatty acid oxidation, leading to accumulation of long-chain fatty acids inside the mitochondria. This is followed by uncoupling oxidative phosphorylation, causing diminished adenosine triphosphate production, which in turn would contribute to depletion of glycogen stores and subsequent hypoglycaemia. 1458. What causes the plant irritation?
Manno, J. E., Fochtman, F. W., Winek, C. L. & Shanor, S. P. (1967). Toxicity of plants of the genus Dieffenbachia. Toxic. appl. Pharmac. 10, 405. Certain plants of the genus Dieffenbachia produce severe irritation of the oral cavity on ingestion. The irritating factor has not yet been identified, but saponins are not involved and the results reported in this preliminary communication eliminate calcium oxalate (I) crystals and suggest instead that a protein may be implicated. Experiments in rabbits show that the fresh juice of D. picta (1I) is much more irritant than that of D. exotica (III) both to the eye and the buccal cavity. In fact a concentrated suspension of a protein-containing centrifugate of the juice of III had to be used to produce the swelling of the tongue and irritation of the oral cavity characteristically induced by II. It was also found that the eye-irritant properties of I! and III were completely destroyed by storing the fruit juice for 24 hr. No eye irritation was produced by a 0.15 70 suspension of I (the concentration present in the juices) and a much higher concentration (5 70) caused no buccal irritation in rats. Attempts are being made to identify a protein isolated from the juice o f l I I and thought to be the irritant factor. 1459. Steady with the slimming Pittman, F. E. (1966). Primary malabsorption following extreme attempts to lose weight. Gut 7, 154. The malabsorption syndrome, evident in most cases of coeliac disease, is associated with an intolerance of wheat and rye gluten (I) (Cited in F.C.T. 1966, 4, 125). Two most unusual cases are now reported in which this syndrome, with typical symptoms of fatty diarrhoea, multiple nutritional deficiencies and characteristic degenerative changes in the mucosa o f the small intestine, was precipitated in two obese adults by extreme measures