1 reversible inhibitor 2 irreversible inhibitor 1 Kinetically

1. reversible inhibitor

2. irreversible inhibitor

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 S 1 的時候，反應中的 S 2 濃度要飽和 (使 S 2 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 If A has no influence on B binding purely random!

Sequential (single-displacement)reactions (2)Ordered A、B非競爭； A、P競爭 Reaction between A and B occurs in the ternary complex and is usually followed by an ordered release of the products, P and Q.

Ping-Pong reactions A 與 B 不競爭 A 與 Q 競爭 Formation of a covalently modified enzyme intermediate. (E’) The product of the enzyme’s reaction with A (called P in the above scheme) is released prior to reaction of the enzyme with the second substrate, B.

Double. Displacement Reaction

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 might favour uncompetitive inhibition.

Enzyme inhibition in open systems. Superiority of uncompetitive agents • Investigations of the open system behavior of reversible dead-end inhibitors were carried out by means of computer simulations and experimental studies. The results from both approaches indicate that substrate-competitive inhibition may often be an inappropriate basis for design of potential therapeutic agents. The use of uncompetitive (also called anticompetitive) inhibitors in this role is likely to be far more effective. Chemical analogs of pathogenspecific enzymic reaction products rather than analogs of substrates provide a promising basis for the systematic design of such uncompetitive inhibitors.