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首页> 外文期刊>Archives of Biochemistry and Biophysics >The interaction of microsomal cytochrome P450 2B4 with its redox partners, cytochrome P450 reductase and cytochrome b5
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The interaction of microsomal cytochrome P450 2B4 with its redox partners, cytochrome P450 reductase and cytochrome b5

机译:微粒体细胞色素P450 2B4及其氧化还原伙伴,细胞色素P450还原酶和细胞色素b5的相互作用

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Cytochrome P450 2B4 is a microsomal protein with a multi-step reaction cycle similar to that observed in the majority of other cytochromes P450. The cytochrome P450 2B4-substrate complex is reduced from the ferric to the ferrous form by cytochrome P450 reductase. After binding oxygen, the oxyferrous protein accepts a second electron which is provided by either cytochrome P450 reductase or cytochrome b5. In both instances, product formation occurs. When the second electron is donated by cytochrome b5, catalysis (product formation) is ~10- to 100-fold faster than in the presence of cytochrome P450 reductase. This allows less time for side product formation (hydrogen peroxide and superoxide) and improves by ~15% the coupling of NADPH consumption to product formation. Cytochrome b5 has also been shown to compete with cytochrome P450 reductase for a binding site on the proximal surface of cytochrome P450 2B4. These two different effects of cytochrome b 5 on cytochrome P450 2B4 reactivity can explain how cytochrome b 5 is able to stimulate, inhibit, or have no effect on cytochrome P450 2B4 activity. At low molar ratios (<1) of cytochrome b5 to cytochrome P450 reductase, the more rapid catalysis results in enhanced substrate metabolism. In contrast, at high molar ratios (1) of cytochrome b 5 to cytochrome P450 reductase, cytochrome b5 inhibits activity by binding to the proximal surface of cytochrome P450 and preventing the reductase from reducing ferric cytochrome P450 to the ferrous protein, thereby aborting the catalytic reaction cycle. When the stimulatory and inhibitory effects of cytochrome b5 are equal, it will appear to have no effect on the enzymatic activity. It is hypothesized that cytochrome b 5 stimulates catalysis by causing a conformational change in the active site, which allows the active oxidizing oxyferryl species of cytochrome P450 to be formed more rapidly than in the presence of reductase.
机译:细胞色素P450 2B4是一种微粒体蛋白,具有多步反应周期,与大多数其他细胞色素P450中观察到的相似。细胞色素P450 2B4底物复合物通过细胞色素P450还原酶从铁形式还原为亚铁形式。结合氧后,氧化亚铁蛋白接受由细胞色素P450还原酶或细胞色素b5提供的第二个电子。在这两种情况下,都会形成产品。当细胞色素b5给第二个电子时,催化作用(产物形成)比存在细胞色素P450还原酶时快约10至100倍。这样可以减少副产物(过氧化氢和超氧化物)形成的时间,并将NADPH消耗与产物形成的耦合提高约15%。还已经表明细胞色素b5与细胞色素P450还原酶竞争细胞色素P450 2B4近端表面上的结合位点。细胞色素b 5对细胞色素P450 2B4反应性的这两种不同作用可以解释细胞色素b 5如何刺激,抑制或不影响细胞色素P450 2B4活性。在细胞色素b5与细胞色素P450还原酶的摩尔比低(<1)时,更快的催化作用会增强底物代谢。相反,在细胞色素b 5与细胞色素P450还原酶的摩尔比高(1)时,细胞色素b5通过与细胞色素P450的近端表面结合并抑制还原酶将三价细胞色素P450还原为亚铁蛋白而抑制活性,从而中止了催化作用。反应周期。当细胞色素b5的刺激和抑制作用相等时,似乎对酶活性没有影响。假设细胞色素b 5通过在活性位点引起构象变化来刺激催化作用,这使得细胞色素P450的活性氧化氧基氧化物种比在还原酶存在下更快地形成。

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