Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic origin of dicarboxylic acids which are produced as a result of hypoglycin poisoning (Jamaican vomiting sickness) was investigated. 14C- and 3H-labelled palmitic acid was administered with hypoglycin to rats, and radioactivity was measured in urinary dicarboxylic acids that were isolated by gas-liquid chromatography. Both isotopes were incorporated into adipic and sebacic acids, indicating a precursor-product relationship. Glutaric acid was, essentially, unlabelled. Preferential incorporation of C-16, relative to C-1 of palmitate, while not evident from data for fraction of isotopic dose incorporated, could be deduced by comparing ratios of 14C:3H in precursor with those ratios in products. It thus appears that omega-oxidation of the fatty acid intervenes predominantly at an intermediate stage of chain-shortening, when inhibition of beta-oxidation by hypoglycin becomes more pronounced.
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PMID:The biogenesis of dicarboxylic acid in rats given hypoglycin. 673 31

Azaspiracid (AZA) poisoning was unknown until 1995 when shellfish harvested in Ireland caused illness manifesting by vomiting and diarrhoea. Further in vivo/vitro studies showed neurotoxicity linked with AZA exposure. However, the biological target of the toxin which will help explain such potent neurological activity is still unknown. A region of Irish coastline was selected and shellfish were sampled and tested for AZA using mass spectrometry. An outbreak was identified in 2010 and samples collected before and after the contamination episode were compared for their metabolite profile using high resolution mass spectrometry. Twenty eight ions were identified at higher concentration in the contaminated samples. Stringent bioinformatic analysis revealed putative identifications for seven compounds including, glutarylcarnitine, a glutaric acid metabolite. Glutaric acid, the parent compound linked with human neurological manifestations was subjected to toxicological investigations but was found to have no specific effect on the sodium channel (as was the case with AZA). However in combination, glutaric acid (1 mM) and azaspiracid (50 nM) inhibited the activity of the sodium channel by over 50%. Glutaric acid was subsequently detected in all shellfish employed in the study. For the first time a viable mechanism for how AZA manifests itself as a toxin is presented.
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PMID:New insights into the causes of human illness due to consumption of azaspiracid contaminated shellfish. 2592 56