Marine Excitatory Amino Acids: Structure, Properties, Biosynthesis and Recent Approaches to Their Syntheses

Abstract

<jats:p>This review considers the results of recent studies on marine excitatory amino acids, including kainic acid, domoic acid, dysiherbaine, and neodysiherbaine A, known as potent agonists of one of subtypes of glutamate receptors, the so-called kainate receptors. Novel information, particularly concerning biosynthesis, environmental roles, biological action, and syntheses of these marine metabolites, obtained mainly in last 10–15 years, is summarized. The goal of the review was not only to discuss recently obtained data, but also to provide a brief introduction to the field of marine excitatory amino acid research.</jats:p>

Current Trends and New Challenges in Marine Phycotoxins

“…Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS), though it is also expressed in peripheral tissues [ 142 ]. It binds to ionotropic glutamate receptors (iGluRs) [ 143 ], which are also the target for a variety of natural occurring toxins, such as domoic acid (DA) [ 144 ]. DA causes amnesic shellfish poisoning (ASP), named after the memory loss observed [ 145 ].…”

“…DA is a hydrophilic amino acid with several isomers, isodomoic acid A-H and epi-domoic acid [ 146 ], but only a few were detected in seafood products [ 147 ]. Domoic acid is a known agonist of iGluRs, which maintains them at an open state, triggering neuron excitability ( Figure 2 ) [ 144 ]. Three functional classes of iGluRs are currently identified: kainate receptors, AMPA receptors, and NMDA receptors [ 148 ].…”

“…However, these structures are based on LBD soluble form; thus, these conformation modifications are to be confirmed by elucidating DA structure bound to full length receptors. Additionally, DA is an agonist not only of kainate receptors but also AMPA receptors [ 144 , 146 ]. High-resolution conformational changes induced by DA in AMPA receptors in the LBD or in the full-length receptor have not been revealed yet.…”

“…Kainate and AMPA receptors excitability implies Ca 2+ and Na + influx into neurons, which, in turn, activates NMDA receptors and glutamatergic signaling [ 144 , 147 ]. This is the mechanism through which DA causes ASP symptomatology [ 146 ].…”

Editorial to the Special Issue: “Dedicated to the 55th Anniversary of G.B. Elyakov Pacific Institute of Bioorganic Chemistry of the Far Eastern Branch of the Russian Academy of Sciences”

“…These studies began in the 60s of the last century, but they remain relevant to this day [ 1 ]. In the review written by Valentin Stonik and Inna Stonik [ 2 ], the information concerning biosynthesis, environmental roles, biological action, and syntheses of marine excitatory amino acids, including kainic acid, domoic acid, dysiherbaine, and neodysiherbaine A, is summarized.…”