Phycotoxins: chemistry, mechanisms of action and shellfish poisoning

Phycotoxins are natural metabolites produced by micro-algae. Through accumulation in the food chain, these toxins may concentrate in different marine organisms, including filter-feeding bivalves, burrowing and grazing organisms, herbivorous and predatory fish. Human poisoning due to ingestion of seafood contaminated by phycotoxins has occurred in the past, and harmful algal blooms (HAB) are naturally occurring events. Still, we are witnessing a global increase in HABs and seafood contaminations, whose causative factors are only partially understood. Phycotoxins are small to medium-sized natural products and belong to many different groups of chemical compounds. The molecular weight ranges from ca. 300 to over 3000 dalton, and the compound classes represented include amino acids, alkaloids and polyketides. Each compound group typically has several main compounds based on the same or similar structure. However, most groups also have several analogues which are either produced by the algae or through metabolism in fish or shellfish or other marine organisms.The different phycotoxins have distinct molecular mechanisms of action. Saxitoxins, ciguatoxins, brevetoxins, gambierol, palytoxins, domoic acid, and, perhaps, cyclic imines, alter different ion channels and/or pumps at the level of the cell membrane. The normal functioning of neuronal and other excitable tissues is primarily perturbed by these mechanisms, leading to adverse effects in humans. Okadaic acid and related compounds inhibit serine/threonine phosphoprotein phosphatases, and disrupt major mechanisms controlling cellular functions. Pectenotoxins bind to actin filaments, and alter cellular cytoskeleton. The precise mechanisms of action of yessotoxins and azaspiracids, in turn, are still undetermined.The route of human exposure to phycotoxins most often is oral, although living systems may become exposed to phycotoxins through other routes. Based on recorded symptoms, the major poisonings recognized so far include paralytic, neurotoxic, amnesic, diarrhoeic shellfish poisonings, ciguatera, as well as palytoxin and azaspiracid poisonings.