DOMOIC ACID

Chemical Properties

Off-White Solid

Uses

Labelled Domoic Acid. Domoic Acid is an excitatory amino acid isolated from the red alga Chondria armata Okamura, Rhodomelaceae. Domoic acid shown to be responsible for amnesic shellfish poisoning ass ociated with ingestion of certain cultured blue mussels. Domoic Acid is a structural analog of Kainic acid (K135000).

Uses

Domoic acid has been used:

• as an excitatory neurotoxin to determine brain transcriptional response
• to study its cytotoxic, genotoxic and immunotoxic effects on the marine mussel M. edulis
• to study its neurobehavioral effects on mouse fetuses

Uses

Domoic Acid is an excitatory amino acid isolated from the red alga Chondria armata Okamura, Rhodomelaceae. Domoic acid shown to be responsible for amnesic shellfish poisoning associated with ingestion of certain cultured blue mussels. Domoic acid is a structural analog of Kainic acid (K135000). DA. EU regulated marine toxin.

Definition

ChEBI: A L-proline derivative that is L-proline substituted by a carboxymethyl group at position 3 and a 6-carboxyhepta-2,4-dien-2-yl group at position 4. It is an analog of kainic acid and is the neurotoxin associated with the a nesic shellfish poisoning (ASP).

General Description

Domoic acid, a heterocyclic amino acid neurotoxin is synthesized by various marine algaes. It possess some structural similarity to kainic acid.

Biological Activity

More potent and possibly more selective than kainate at kainate receptors, as demonstrated in electrophysiological studies.

Biochem/physiol Actions

Domoic acid is a potent agonist at receptors for excitatory amino acids glutamate and kainate. It has highest affinity for AMPA/kainate receptor of any kainate agonist. It can causes excessive excitation of neurons leading to depletion of energy stores.

Synthesis

A method using marine diatom symbiotic bacteria fermentation:
1) Strain activation.
2) Seed culture preparation: medium sterilization, inoculation, and aerobic cultivation.
3) Fermentation: inoculating the seed culture into fermentation medium under similar conditions for 48-52h.
4) Extraction: filtering the broth, extracting the biomass with methanol three times, combining and concentrating the extracts.
5) Purification: eluting the crude extract, collecting the target fraction, and evaporating to obtain a white powder.

Purification Methods

Domoic acid (~300 mg) is purifed on a Dowex1 column (3.5 x 40 mm, 200-400 mesh, acetate form), washed with H2O until neutral, then eluted with increasing concentrations of AcOH (8L) from 0 to 0.25M. The fraction containing domoic acid (in 50mL) is collected, evaporated to dryness under reduced pressure and recrystallised from aqueous EtOH. It is a glutamate and a Kainate receptor agonist. [Impellizzeri et al. Phytochemistry 14 1549 1975, Takemoto & Diago Arch Pharm 293 627 1960, Beilstein 22/4 V 371.]