Domoic acid
Names | |
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Preferred IUPAC name
(2S,3S,4S)-4-[(2Z,4E,6R)-6-Carboxyhepta-2,4-dien-2-yl]-3-(carboxymethyl)pyrrolidine-2-carboxylic acid | |
Identifiers | |
3D model (
JSmol ) |
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ChEBI | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard
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100.159.099 |
EC Number |
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IUPHAR/BPS |
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PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
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: | |
Warning | |
H302, H312, H332 | |
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 [77 °F], 100 kPa).
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Domoic acid (DA) is a
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.[citation needed]
Domoic acid was first isolated in 1959 from a species of red algae,
In 1961, seabirds attacked the Capitola area in California, and though it was never confirmed, it was later hypothesized that they were under the influence of domoic acid.[4]
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.[5]
Domoic acid has been suggested to have been involved in an incident which took place on June 22, 2006, when a
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. [7]
Chemistry
General
Domoic acid is a structural analog of
Biosynthesis
In 1999, using
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.[10] 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).
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
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.[1]
Mechanism of action
The effects of domoic acid have been attributed to several mechanisms, but the one of concern is through
In the brain, domoic acid especially damages the
Humans | Animals |
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vomiting | head weaving |
nausea | seizures |
diarrhea and abdominal cramps within 24 hours of ingestion |
bulging eyes |
headache | mucus from the mouth |
dizziness | disorientation and aggressiveness |
confusion, disorientation | death |
loss of short-term memory | |
motor weakness | |
seizures | |
profuse respiratory secretions | |
cardiac arrhythmias | |
coma and possible death | |
References for all, unless otherwise noted:[5] |
Toxicology
Domoic acid producing algal blooms are associated with the phenomenon of
Studies have shown that there are no symptomatic effects in humans at levels of 0.5 mg/kg of body weight. In the 1987 domoic acid poisoning on Prince Edward Island concentrations ranging from 0.31 to 1.28 mg/kg of muscle tissue were noted in people that became ill (three of whom died). Dangerous levels of domoic acid have been calculated based on cases such as the one on Prince Edward island. The exact LD50 for humans is unknown; for mice the LD50 is 3.6 mg/kg.[5]
New research has found that domoic acid is a heat-resistant and very stable toxin, which can damage kidneys at concentrations that are 100 times lower than what causes neurological effects.[12]
Diagnosis and prevention
In order to be diagnosed and treated if poisoned, domoic acid must first be detected. Methods such as
There is no known antidote available for domoic acid. Therefore, if poisoning occurs, it is advised to go quickly to a hospital. Cooking or freezing affected fish or shellfish tissue that are contaminated with domoic acid does not lessen the toxicity.[14]
As a public health concern, the concentration of domoic acid in shellfish and shellfish parts at point of sale should not exceed the current permissible limit of 20 mg/kg tissue. In addition, during processing shellfish, it is important to pay attention to environmental condition factors.[15]
In popular culture
On August 18, 1961, in Capitola and Santa Cruz, California there was an invasion of what people described as chaotic seabirds. These birds were believed to be under the influence of domoic acid, and it inspired a scene in Alfred Hitchcock's feature film The Birds.[16]
In addition domoic acid was used to poison a witness in the Elementary Season 1 Episode 13: "The Red Team".[17]
Domoic acid overtakes Camp Kikiwaka causing the campers to develop bizarrely altered personalities in the TV Series Bunk'd Season 2 Episode 10.[citation needed]
See also
- Canadian Reference Materials
- Pseudo-nitzschia
- Quisqualic acid
- Brevetoxin
- Ciguatoxin
- Okadaic acid
- Saxitoxin
- Maitotoxin
References
- ^ .
- ^ "Domoic Acid Toxicity". The Marine Mammal Center. Retrieved 2 April 2015.
- PMID 27917011.
- ^ "DOMOIC ACID - A major concern to washington state's shellfish lovers". Washington Department of Fish and wildlife. Archived from the original on 3 December 2013. Retrieved 12 April 2015.
- ^ a b c Gilbert S. "Domoic Acid". Toxipedia. Archived from the original on 5 May 2015. Retrieved 15 April 2015.
- ^ "Possibly drunk pelican hits windshield". NBC news. 2006-06-24. Retrieved 12 April 2015.
- ^ "'It was just total fear': California teen describes being attacked by sea lion". ABC News. Retrieved 21 June 2019.
- S2CID 22318425.
- PMID 10223629.
- ^ PMID 30262498.
- PMID 18728725.
- ^ a b Smith T. "Toxin in seafood causes kidney damage in mice at levels considered safe for consumption". avante medical center. Archived from the original on 2019-02-14. Retrieved 2015-04-30.
- ^ "Detection and Analysis of Marine Biotoxins". Northwest fisheries science center. Archived from the original on 2016-03-04. Retrieved 2015-04-30.
- ^ "Domoic Acid - A Major Concern to Washington State's Shellfish Lovers". washington department of fish and wildlife. Archived from the original on 2013-12-03. Retrieved 2012-04-08.
- PMID 20120452.
- S2CID 128391841.
- ^ "Elementary s01e13 Episode Script | SS". Springfield! Springfield!.
External links
- "Domoic Acid and Pseudo-nitzschia References". Fisheries and Oceans Canada. Archived from the original on 2013-12-04.
- "Amnesic Shellfish Poisoning, Domoic Acid, and Pseudo-nitzschia". International Society for the Study of Harmful Algae ISSHA. Archived from the original on 2013-12-03. Retrieved 2010-05-07.
- "Domoic acid". IPCS INCHEM.
- "Domoic Acid - A Major Concern to Washington State's Shellfish Lovers". Washington Department of Fish and Wildlife. Archived from the original on 2013-12-03. Retrieved 2012-04-08.
- "Domoic Acid Toxicity".