domoic acid domoic acid domoic acid (da) is a kainic acid-type neurotoxin that causes amnesic shellfish poisoning (asp). it is produced by algae and accumulates in shellfish, sardines, and anchovies. when sea lions, otters, cetaceans, humans, and other predators eat contaminated animals, poisoning may result. exposure to this compound affects the brain, causing seizures, and possibly death. domoic acid names preferred iupac name (2s,3s,4s)-4--3-(carboxymethyl)pyrrolidine-2-carboxylic acid identifiers cas number 14277-97-5 y 3d model (jsmol) interactive image chebi chebi:34727 y chembl chembl1232313 n chemspider 4445428 y echa infocard 100.159.099 ec number 630-802-1 iuphar/bps 4181 pubchem cid 5282253 unii m02525818h y comptox dashboard (epa) dtxsid20274180 inchi inchi=1s/c15h21no6/c1-8(4-3-5-9(2)14(19)20)11-7-16-13(15(21)22)10(11)6-12(17)18/h3-5,9-11,13,16h,6-7h2,1-2h3,(h,17,18)(h,19,20)(h,21,22)/b5-3+,8-4-/t9-,10+,11-,13+/m1/s1 ykey: vzfrncsocopndb-aokdlofssa-n yinchi=1/c15h21no6/c1-8(4-3-5-9(2)14(19)20)11-7-16-13(15(21)22)10(11)6-12(17)18/h3-5,9-11,13,16h,6-7h2,1-2h3,(h,17,18)(h,19,20)(h,21,22)/b5-3+,8-4-/t9-,10+,11-,13+/m1/s1key: vzfrncsocopndb-aokdlofsbm smiles o=c(o)1nc(/c(=c\c=c\(c(=o)o)c)c)1cc(=o)o properties chemical formula c15h21no6 molar mass 311.334 g·mol−1 density 1.273 g/cm3 vapor pressure 2.62×10−16 mmhg (34.9 fpa) hazards ghs labelling: pictograms signal word warning hazard statements h302, h312, h332 precautionary statements p261, p264, p270, p271, p280, p301+p312, p302+p352, p304+p312, p304+p340, p312, p322, p330, p363, p501 except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). n verify (what is yn ?) infobox references history there has been little use of domoic acid throughout history except for in japan, where it has been used as an anthelmintic for centuries. domoic acid was first isolated in 1959 from a species of red algae, chondria armata, in japan, which is commonly referred to as dōmoi (ドウモイ) in the tokunoshima dialect, or hanayanagi. poisonings in history have been rare, or undocumented; however, it is thought that the increase in human activities is resulting in an increasing frequency of harmful algal blooms along coastlines in recent years. in 2015, the north american pacific coast was heavily impacted by an algal bloom, consisting predominantly of the domoic acid-producing pennate diatom, pseudo-nitzschia. consequently, elevated levels of domoic acid were measured in stranded marine mammals, prompting the closure of beaches and damaging razor clam, rock crab and dungeness crab fisheries. in 1961, seabirds attacked the capitola area in california, and though it was never confirmed, they were thought to be under the influence of domoic acid. in 1987, in prince edward island, canada, there was a shellfish poisoning resulting in 3 deaths. blue mussels (mytulis edulis) contaminated with domoic acid were blamed. domoic acid has been suggested to have been involved in an incident which took place on june 22, 2006, when a california brown pelican flew through the windshield of a car on the pacific coast highway. on friday, june 14, 2019, a teenager was attacked and injured by a sea lion that was alleged to be under the influence of domoic acid in pismo beach on the central california coast chemistry general domoic acid is a structural analog of kainic acid, proline, and endogenous excitatory neurotransmitter glutamate. ohfune and tomita, who wanted to investigate its absolute stereochemistry, were the first and only to synthesize domoic acid in 1982. biosynthesis in 1999, using 13c- and 14c-labelled precursors, the biosynthesis of domoic acid in the diatom genus pseudo-nitzschia was examined. after addition of -acetate, nmr spectroscopy showed enrichment of every carbon in domoic acid, indicating incorporation of the carbon isotopes. this enrichment was consistent with two biosynthetic pathways. the labeling pattern determined that domoic acid can be biosynthesized by an isoprenoid intermediate in combination with a tricarboxylic acid (tca) cycle intermediate. in 2018, using growth conditions known to induce domoic acid production in pseudo-nitzschia multiseries, transcriptome sequencing successfully identified candidate domoic acid biosynthesis genes responsible for the pyrrolidine core. these domoic acid biosynthesis genes, or ‘dab’ enzymes were heterologously expressed, characterized, and annotated as daba (terpene cyclase), dabb (hypothetical protein), dabc (α-ketoglutarate–dependent dioxygenase), and dabd (cyp450).simplified domoic acid biosynthetic pathway, with all pertinent structures, enzymes, and cofactors listed as described by brunson et al., in their article "biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom".domoic acid biosynthesis begins with the daba-catalyzed geranylation of l-glutamic acid (l-glu) with geranyl pyrophosphate (gpp) to form n-geranyl-l-glutamic acid (l-ngg). dabd then performs three successive oxidation reactions at the 7′-methyl of l-ngg to produce 7′-carboxy-l-ngg, which is then cyclized by dabc to generate the naturally occurring isodomoic acid a. finally, an uncharacterized isomerase could convert isodomoic acid a to domoic acid. further investigation is needed to resolve the final isomerization reaction to complete the pathway to domoic acid. synthesis synthesis of domoic acid as described by jonathan clayden, benjamin read and katherine r. hebditch, in their article chemistry of domoic acid, isodomoic acids, and their analogues. using intermediates 5 and 6, a diels-alder reaction produced a bicyclic compound (7). 7 then underwent ozonolysis to open the six-membered ring leading to selenide (8). 8 was then deselenated to form 9 (e-9 and z-9), lastly leading to the formation of (-) domoic acid. mechanism of action the effects of domoic acid have been attributed to several mechanisms, but the one of concern is through glutamate receptors. domoic acid is an excitatory amino acid analogue of glutamate; a neurotransmitter in the brain that activates glutamate receptors. domoic acid has a very strong affinity for these receptors, which results in excitotoxicity initiated by an integrative action on ionotropic glutamate receptors at both sides of the synapse, coupled with the effect of blocking the channel from rapid desensitization. in addition there is a synergistic effect with endogenous glutamate and n-methyl-d-aspartate receptor agonists that contribute to the excitotoxicity. in the brain, domoic acid especially damages the hippocampus and amygdaloid nucleus. it damages the neurons by activating ampa and kainate receptors, causing an influx of calcium. although calcium flowing into cells is normal, the uncontrolled increase of calcium causes the cells to degenerate. because the hippocampus may be severely damaged, short-term memory loss occurs. it may also cause kidney damage – even at levels considered safe for human consumption, a new study in mice has revealed. the kidney is affected at a hundred times lower than the concentration allowed under fda regulations. symptoms of domoic acid humansanimals vomitinghead weaving nauseaseizures diarrhea and abdominal crampswithin 24 hours of ingestionbulging eyes headachemucus from the mouth dizzinessdisorientation confusion, disorientationdeath loss of short-term memory motor weakness seizures profuse respiratory secretions cardiac arrhythmias coma and possible death