Hypoglycin, the famous toxin of the unripe Jamaican ackee fruit

Sherratt, H. S. A.

doi:10.1016/0165-6147(86)90310-x

Cited by 79 publications

(63 citation statements)

References 15 publications

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“…Beta-oxidation is also suppressed by MCPA's inhibition of the different short-chain acyl-CoA dehydrogenases, particularly butyryl-CoA dehydrogenase (1,22,(24)(25)(26)29). This leads to accumulation of short-chain fatty acids in the serum (e.g., propionic, n-butyric, and isovaleric acid).…”

Section: Mechanism Of Hypoglycin Toxicitymentioning

confidence: 95%

Ackee Fruit Poisoning: An Outbreak Investigation in Haiti 2000–2001, and Review of the Literature

Joskow

Belson

Vesper

et al. 2006

Clinical Toxicology

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The Centers for Disease Control and Prevention (CDC) provided technical assistance to the Ministry of Health of Haiti during an outbreak of over 100 cases of acute illness and death in the northern region of Haiti during a 4-month period beginning in November 2000. The epidemiologic, clinical, and laboratory findings in this investigation indicated the ingestion of unripe ackee fruit as the most likely cause of this outbreak. This report describes the CDC field investigation in Haiti and gives a brief overview of the current state of knowledge about ackee poisoning.

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Section: Mechanism Of Hypoglycin Toxicitymentioning

confidence: 95%

Ackee Fruit Poisoning: An Outbreak Investigation in Haiti 2000–2001, and Review of the Literature

Joskow

Belson

Vesper

et al. 2006

Clinical Toxicology

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“…In the case of both 4-pentenoic acid and methylenecyclopropylacetic acid, metabolic activation by the ~-oxidation pathway is believed to convert these unsaturated substrates into highly reac- tive, electrophilic intermediates which bind to, and thereby inhibit, components of the ~-oxidation enzyme complex [25][26][27]. If the structural parallel between A4-VPA and these unsaturated acids extends to their respective pathways of metabolism, one would anticipate that A4-VPA also would undergo metabolic activation in mammalian liver to electrophilic species, such as the conjugated diene, 2-n-propyl-2(E),4-pentadienoic acid (A2(E),~-VPA; 4, Fig.…”

Section: 'A 4 Pathway' Of Valproate Metabolismmentioning

confidence: 99%

Metabolism of valproate to hepatotoxic intermediates

Baillie

1992

Pharmaceutisch Weekblad Scientific Edition

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A number of lines of evidence indicate that metabolites of valproate rather than the parent drug, mediate the microvesicular steatosis which characterizes valproate-associated liver injury. In this article, two mechanisms are discussed whereby valproate may cause hepatic steatosis through interference with the process of fatty acid beta-oxidation. In the first, valproate itself enters the mitochondrion where it completes for the enzymes and/or co-factors involved in the beta-oxidation of endogenous substrates, while in the second, valproate is metabolized via the hepatotoxic terminal olefin, delta 4-valproate, to a variety of chemically reactive intermediates which inhibit key enzymes in the beta-oxidation cycle.

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“…Such products mainly represent ketone bodies and, to a small extent, citric acid cycle intermediates (28,29,40). We verified from measurement of the KCN-inhibitable activity that mitochondria mediated at least 80% of the oxidation of [U-14C]palmitate (41).…”

Section: Animalsmentioning

confidence: 99%

Decreased mitochondrial oxidation of fatty acids in pregnant mice: Possible relevance to development of acute fatty liver of pregnancy

et al. 1993

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Severe impairment of the beta-oxidation of fatty acids, as a consequence of a single factor or a combination of different causes, leads to microvesicular steatosis of the liver. In an effort to understand the mechanism(s) leading to the development of acute fatty liver of pregnancy in some women, we determined the effects of pregnancy on the mitochondrial oxidation of fatty acids in mice. In vivo, the rate of oxidation of the whole fatty-acid chain length was determined by measuring the rate of exhalation of [14C]CO2 after intragastric administration of a tracer dose of [U-14C]palmitic acid. [14C]CO2 exhalation was not significantly decreased at 14 days of gestation, but it had declined by 40% at 18 days of gestation (i.e., 24 to 48 hr before delivery). The rate of first beta-oxidation cycle was assessed by measuring the rate of [14C]CO2 exhalation after administration of [1-14C]octanoic acid, [1-14C]butyric acid or [1-14C]palmitic acid. [14C]CO2 exhalation had declined by 60%, 46%, and 24% after administration of [1-14C]octanoic acid, [1-14C]butyric acid and [1-14C]palmitic acid, respectively, in 18-day-pregnant mice. Total hepatic lipids and triglycerides, expressed per gram of liver, remained unchanged in 18-day-pregnant mice. In vitro, the rate of mitochondrial beta-oxidation (expressed per milligram of protein) had decreased by 47% at 18 days' gestation with [U-14C]palmitic acid as substrate and by 33% with [1-14C]octanoic acid but remained unchanged with [1-14C]palmitic acid. The activity of the tricarboxylic acid cycle, assessed by the formation of [14C]CO2 from [1-14C]acetic acid, had decreased by 24%. We conclude that the mitochondrial oxidation of fatty acids decreased during late-term pregnancy in mice as a consequence of both decreased mitochondrial beta-oxidation of medium-chain fatty acids, and decreased activity of the tricarboxylic acid cycle. We suggest that this effect, in combination with other factors, may contribute to the development of fatty liver of pregnancy in some pregnant women.

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Hypoglycin, the famous toxin of the unripe Jamaican ackee fruit

Cited by 79 publications

References 15 publications

Ackee Fruit Poisoning: An Outbreak Investigation in Haiti 2000–2001, and Review of the Literature

Ackee Fruit Poisoning: An Outbreak Investigation in Haiti 2000–2001, and Review of the Literature

Metabolism of valproate to hepatotoxic intermediates

Decreased mitochondrial oxidation of fatty acids in pregnant mice: Possible relevance to development of acute fatty liver of pregnancy

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