抑制劑(inhibitor).pptVIP

生化統整 第三組 李秋霖0993B031 黃三珊0993B040 抑制劑(Inhibitor) 干擾酵素作用降低其活性 其影響酵素有兩種方式: 1.reversible inhibitor:和酵素結合後再分開,使酵素回到原本狀態 　　　→依結合在active site 和 other site區分 　　　　? Competitive inhibition 　　　　? Noncompetitive inhibition 　　　　? Uncompetitive inhibition 2.irreversible inhibitor:與酵素結合後成為新的蛋白質,不具酵素活性 Uncompetitive Inhibition: 1.Kinetically 和noncometitive inhibition很像， binding 在active site以外的其他部位，但是　　　　永遠地改變酵素構型 2.對酵素進行共價修飾，使其失去活性且無法恢復 3.如此使酵素“自殺”的I，我們稱之為suicide inhibitor。例如:Pencillin is an irreversible inhibitor of glycopeptide transpeptidase 雙質子反應（bimolecular kinetics） 雙基質反應仍可適用於 M-M 公式，但?兩種基質的?Km?要分別測定；測 S1 的時候，反應中的 S2 濃度要飽和?(使 S2 成為非主導因子)，反之亦然 1.Sequential (single-displacement)reactions （ㄧ個速率限制步驟） 　(1)Random (2)Ordered 先結合 leading substrate 類似 noncompetitive inhibition 2.Ping-pong (double-displacement)reactions 類似 uncompetitive inhibition Sequential (single-displacement)reactions (1)Random A、B非競爭 AEB to PEQ is the Rate-Limiting Step Sequential (single-displacement)reactions (2)Ordered A、B非競爭； A、P競爭 Ping-Pong reactions DoubleDisplacement Reaction 三、習題解說 競爭型抑制劑結合到活化部位，至受質不能。非競爭行一至計結合再活性部位以外的位置，受質仍可結合，但因為結合抑制劑仍存在，至酵素無法催化反應 許多臨床用來抗微生物感染、抗發炎及抗癌化療藥物都是酵素之可逆抑制劑（reversible inhibitor）。請問這些抑制劑的酵素活性抑制型態有那三種？如何運用酵素動力學（Michaelis-Menten kinetics）來決定抑制型態與抑制劑的結合常數KI呢？ 1. Competitive Inhibitors: 2. Nonompetitive Inhibitors : 3. Unompetitive Inhibitors : Why is uncompetitive inhibition so rare? A possible explanation, with implications for the design of drugs and pesticides. A possible explanation may be that uncompetitive inhibition of an enzyme in a metabolic pathway can have enormously larger effects on the concentrations of metabolic intermediates than competitive inhibition, under circumstances where their effects on the kinetics of the isolated enzyme are very similar. The severely toxic effects that an uncompetitive inhibitor might be expected to have may have caused enzymes to have evolved in such a way that there has been selection against structures that mi