tailieunhanh - PDQ BIOCHEMISTRY - PART 7

Điều này được gọi là ức chế cạnh tranh, nơi mà một phân tử giống như một phân tử chất nền (trả tiền đi lại) ức chế một enzyme bằng cách liên kết các trang web hoạt động mà không có một phản ứng tiếp theo diễn ra | 208 PDQ BIOCHEMISTRY ing turnstile traffic and slowing down the passage of commuters into the subway. This is known as competitive inhibition where a molecule that looks like a substrate molecule paying commuter inhibits an enzyme by binding at the active site without a subsequent reaction taking place. Ultimately this nonpaying commuter may be displaced from the turnstile by other paying commuters. However if the subway station is flooded with nonpaying commuters competitive inhibitors prolonged enzyme inhibition will follow. If you remember the velocity versus substrate concentration plots we showed in Chapter 3 the effect of a fixed concentration of competitive inhibitor in this reaction is shown in Figure 7-5. The curve is still hyperbolic but is shifted to the right. It simply means that you need an increased concentration of substrate molecules relative to the inhibitor before you can get up to the maximal enzyme velocity Vmax . Remember that the concentration of substrate that gives one half of the Vmax is called the Km Michaelis constant for the reaction. You can see that the competitive inhibitor increases the value of Km for the enzyme although the Vmax is not altered. It just takes a higher substrate concentration to get to the Vmax a little like putting a piece of foam rubber under the accelerator in your car. You can get to the maximal speed it just takes more pressure on the gas pedal. A specific biochemical example is the enzyme succinate dehydrogenase that converts succinate within the Krebs cycle to the product fumarate Figure 7-6 . It does this by introducing a double bond between the inner two carbons of succinate. Malonate is a competitive inhibitor for this reaction. Like succinate which it resembles malonate does have two -COO- groups but as it has only three carbons it is impossible for the enzyme to create a double bond in this molecule see Figure 7-6 . Thus malonate binds at the active site of the enzyme and cannot be processed. It prevents