Department of Environmental and Forest Biology, State University of New York, Syracuse, College of Environmental Science and Forestry, Syracuse, NY 13210, USA.
Ecotoxicol Environ Saf. 2010 Jul;73(5):757-61. doi: 10.1016/j.ecoenv.2009.12.003. Epub 2010 Jan 13.
Microcystins (MCs) are cyanobacterial toxins that inhibit protein phosphatases 1 and 2A (PP1, PP2A) within an animal through both reversible and covalent interactions. Only MCs that have accumulated in animal tissue in reversible interactions are currently considered when estimating risk to higher trophic levels and humans through food web exposure. However, the majority of MCs is likely covalently bound to target proteins in tissues and these MCs are not quantified or included in these assessments. These covalently bound MCs may be made bioavailable in the digestive system of a consumer through the digestion of their attached protein phosphatase. Three common digestive enzymes, pepsin, chymotrypsin, and trypsin, did not digest cyclic MC-LR and MC-LY, but were very active against a control peptide with typical linkages and standard amino acids in "L" conformation, supporting the possibility for MC-peptide formation during gut passage. To test if digestion products could be biologically active in the consumer, four predicted MC-peptides were synthesized and assayed for activity against PP1 by the protein phosphatase inhibition assay (PPIA). All four MC-peptides were active against PP1 and comparably half (58%) as inhibitory as the parent toxin. This in vitro study demonstrated that MCs covalently bound to proteins may represent a reservoir of potential toxicity for consumers.
微囊藻毒素（MCs）是一种蓝藻毒素，通过可逆和共价相互作用在动物体内抑制蛋白磷酸酶 1 和 2A（PP1、PP2A）。目前，在通过食物网暴露估计对更高营养级和人类的风险时，仅考虑在动物组织中通过可逆相互作用积累的 MCs。然而，组织中大多数 MCs 可能与靶蛋白发生共价结合，这些 MCs未被量化或包含在这些评估中。这些共价结合的 MCs 可能通过附着的蛋白磷酸酶在消费者的消化系统中被生物利用。三种常见的消化酶，胃蛋白酶、胰凝乳蛋白酶和胰蛋白酶，不能消化环状 MC-LR 和 MC-LY，但对具有典型连接和“L”构象标准氨基酸的对照肽非常活跃，支持 MC-肽在肠道通过时形成的可能性。为了测试消化产物在消费者体内是否具有生物活性，合成了四个预测的 MC-肽，并通过蛋白磷酸酶抑制测定（PPIA）测定其对 PP1 的活性。所有四个 MC-肽均对 PP1 具有活性，其抑制作用与母体毒素相当（58%）。这项体外研究表明，与蛋白质共价结合的 MCs 可能代表消费者潜在毒性的一个储库。
