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New article next to Inhibitors 下面的新文章抑制剂

酶抑制

Enzyme inhibitors are molecules that decrease the activity of酶, and knowledge about inhibitors can, for example, be used in developing drugs or in the study of biochemical pathways, because inhibitors provide a way to interfere with these pathways. Enzyme inhibitors can be either irreversible or reversible; irreversible inhibitors decrease enzymatic activity by destroying the enzyme through various mechanisms, while reversible inhibitors keep the enzyme functional. The inhibitors we will study here are reversible inhibitors [1].

抑制类型

酶抑制剂的机制可以分为3个主要组：竞争性抑制剂，非竞争性抑制剂和混合抑制剂。竞争性抑制剂在与底物竞争中与酶的活性位点结合起作用；非竞争性抑制剂与不同活性位点不同的位点的酶 - 底物复合物结合，但它们不能单独与该酶结合，并且混合抑制剂可以与酶和酶 - 覆盖酶和酶 - 卵巢复合物结合在不同于活性的位点的位置[1]。

可以将酶抑制的机理视为延伸到Michaelis-Menten机制and competitive and un-competitive inhibition can be regarded as a special case of mixed inhibition (see Figure 1.a), where K我和K’我are the dissociation constants of the EI and ESI complex, respectively. Using the same approach as that used for deriving the Michaelis-Menten equation (for a detailed derivation, see [2]), the following equation for mixed inhibition can be obtained:

v0= V最大限度•[S] / Km•α+[S]•α’

where α = 1+[I]/K我and α’ = 1+[I]/K’我

Just like the Michealis-Menten equation, this equation can be rearranged to fit a double-reciprocal plot:

1/v0= α’/V最大限度+ Km•α/V最大限度•1/[S]

如果α> 1和α'> 1，则混合抑制作用；为了竞争性抑制，α’= 1;对于非竞争性抑制，α= 1。因此，对于3种不同类型的抑制，获得了3个不同的方程，ALineWeaver-Burk动力学数据的图可以揭示抑制剂执行的抑制类型（见图1.b，1.c和1.d）[1,2]。

At the top is figure 1.a that illustrates the overall enzymatic reaction and the mechanisms of enzyme inhibition as an extension to this. The enzymatic reaction is made up of different steps illustrated in the reaction from left to right, with the formation of enzyme-substrate as the first step in the overall reaction. This step goes both ways, illustrated with a two-directional arrow, with the reversed reaction being the dissociation of the enzyme-substrate into enzyme and substrate again. The next step is the dissociation of the enzyme-substrate into enzyme and product. The addition of inhibitors to the enzyme and the enzyme-substrate complex in the overall enzymatic reaction is also illustrated, where K I and K’ I are the dissociation constants of the enzyme-inhibitor and enzyme-substrate-inhibitor complex, respectively. In addition to this reaction is the enzyme inhibition mechanism which is illustrated below the overall reaction. This reaction is the formation of the enzyme-substrate-inhibitor complex, created from the enzyme-inhibitor complex and substrate. This reaction also goes both ways, illustrated with a two-directional arrow, with the reversed reaction being the dissociation of the enzyme-inhibitor-substrate complex into enzyme-inhibitor complex and substrate. Beneath this illustration are figure 1.b, 1.c, and 1.d. These figures show three different Lineweaver-Burk plots showing the 3 major types of inhibition. Figure 1.b illustrates the competitive inhibition, figure 1.c illustrates the mixed inhibition, and figure 1.d illustrates the un-competitive inhibition. All plots have 1 divided by V on the y-axis and 1 divided by the concentration of substrate on the x-axis. Figure 1.b is a graph with three different lines which represent different datasets with varying inhibitor concentrations and they, therefore, have different slopes. All three lines intersect at the same spot on the y-axis. Next to this plot is figure 1.c which is another graph showing the mixed inhibition as three different lines. These lines represent different datasets with varying inhibitor concentrations and the lines all have different slopes and different y-intercepts. Next to this plot is figure 1.d which is a graph showing the uncompetitive inhibition as three different lines. These lines represent different datasets with varying uncompetitive inhibitor concentrations and the lines have the same slopes. However, the three lines intersect at varying spots on the y-axis

Figure 1:图1.A;总体酶促反应和酶抑制机制的扩展。图1B，C和D；线条框架框图显示了3种主要的抑制类型。如果Y间隔是相同的，但是斜率有所不同，则抑制剂具有竞争力。如果斜率和Y间接率都不同，则混合了抑制剂。如果斜率相同，但是y间接率有所不同，则抑制剂是毫无竞争的。

Methanol poisoning

酶酒精脱氢酶is not completely specific for ethanol; it also catalyzes the formation of aldehydes from other alcohols. One of these alcohols is methanol, which is metabolized into formaldehyde and other toxic compounds that can cause blindness or death [3]. Methanol poisoning is quite common, and can be caused by the ingestion of homemade alcohol. Methanol and ethanol are thus competitive substrates, and ethanol is actually used to prevent poising after the ingestion of methanol, because it inhibits ADH in catalyzing the oxidation of this compound [4].

Calculation of kinetic parameters

See the following pages for details of how to calculate the kinetic parameters for different inhibitors:

Competitive inhibition

非竞争性抑制

Mixed/non-competitive inhibition

参考

  1. Lehninger, Albert L.; Nelson, David L.; Cox, Michael M. (2008).生物化学原理(5th ed.). New York, NY: W.H. Freeman and Company. ISBN 978-0-7167-7108-1.

  2. 阿特金斯，彼得·W。De Paula，Julio；弗里德曼（Ronald）（2009）。Quanta, Matter, and Change: A molecular approach to physical chemistry。牛津大学出版社。ISBN 978-0-19-920606-3。

  3. 比蒂,L。绿色,R。,麦基,k和z, p(2013点) A Systematic Review of Ethanol and Fomepizole Use in Toxic Alcohol Ingestions.出现。医学int。2013，638057。

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