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Chemical Pesticides: Mode of Action and Toxicology - Chapter 5

Enzyme chất ức chế cụ thể Một số thuốc trừ sâu, chẳng hạn như thuốc diệt cỏ ức chế tổng hợp axit amin trong các nhà máy, rất chọn lọc giữa thực vật và động vật và rất mạnh. Các chất ức chế tổng hợp chitin được sử dụng như thuốc trừ sâu cũng rất chọn lọc, bởi vì chỉ có côn trùng và động vật giáp xác (và nấm) chitin. Thuốc diệt nấm đầu tiên được mô tả hiệu quả và có một mức độ cao của chọn lọc, nhưng có khả năng tạo ra các hiệu ứng ở động. | chapter five Specific enzyme inhibitors Some pesticides such as the herbicides inhibiting synthesis of amino acids in plants are extremely selective between plants and animals and very potent. The chitin synthesis inhibitors used as insecticides are also extremely selective because only insects and crustaceans and fungi make chitin. The fungicides first described are also efficient and have a high degree of selectivity but are likely to produce effects in animals and plants because they inhibit enzymes of great importance to many types of organisms. 5.1 Inhibitors of ergosterol synthesis Sterols are important building blocks in the cell s membrane system and many sterols are important hormones. In animal tissues cholesterol is quantitatively most important whereas in fungi we find ergosterol and in plants stigmasterol and ỉ-sitosterol. Most eukaryotic organisms seem to be able to synthesize sterols with acetyl-coenzyme A CoA as the starting material exceptions are insects and some fungi. The pathway is complex with many steps and many enzymes involved. Some steps in the synthesis need oxygen and for example yeast cannot produce sterols when grown completely anaerobically. Therefore yeast fermenting cannot go on forever without oxygen because the oxygen is needed as a co-substrate in sterol synthesis. In spite of the similarity of sterol synthesis in plants fungi and animals the pathway is an excellent target for fungicides. Inhibitors of ergosterol synthesis are the largest group of fungicides with the same target. Most of these fungicides however have various effects on plants and animals as well but have low lethal toxicity. The biosynthesis of sterols is extremely complicated and a good textbook in biochemistry should be consulted e.g. Nelson and Cox 2000 . Let us recapitulate the process 1. Three molecules of acetyl-CoA condense to form mevalonate. 2. Mevalonate is converted to isoprene units isoprene pyrophosphate having five carbons . 3. Six isoprene .