FUNCTION OF CYTOCHROME-B5 IN FATTY ACID DESATURATION BY RAT LIVER MICROSOMES
FUNCTION OF CYTOCHROME-B5 IN FATTY ACID DESATURATION BY RAT LIVER MICROSOMES
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DOI：
10.1093/oxfordjournals.jbchem.a129444
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发表时间：
1971-01-01
影响因子：
2.7
通讯作者：
SATO, R
中科院分区：
文献类型：
--
作者：
OSHINO, N;IMAI, Y;SATO, R
在向大鼠肝微粒体中加入NADPH时，细胞色素b5基于其被NADPH还原与其自身氧化之间的平衡而呈现稳态还原水平。通过加入硬脂酰辅酶A（硬脂酰辅酶A）引发脂肪酸去饱和导致细胞色素的NADPH支持的稳定状态的快速转变，有利于更多的氧化，并且这种转变通过HgCl 2部分抑制微粒体NADPH特异性黄素蛋白而加强。这表明，减少饱和的还原当量的增加利用伴随着细胞色素b5的再氧化的刺激。实际上，硬脂酰辅酶A诱导的移位的幅度大致与所用微粒体的脂肪酸去饱和活性成比例。此外，这种转变受到氰化物的干扰，氰化物抑制去饱和系统的末端组分（“氰化物敏感因子”）。由于NADH还原微粒体结合的细胞色素b5比细胞色素自氧化和整体去饱和反应快得多，因此NADH导致细胞色素b5完全还原，添加硬脂酰辅酶A后未观察到还原水平变化。然而，当NADH-细胞色素b5还原酶被PCMS强烈抑制时，硬脂酰辅酶A确实降低了NADH处理的微粒体中细胞色素b5的稳态还原水平。硬脂酰辅酶A还刺激细胞色素b5的氧化，在所添加的NADH耗尽时可观察到，并且这种刺激再次被氰化物阻止。与微粒体细胞色素b5已被删除到不同程度的温和的蛋白水解消化，硬脂酰辅酶A的去饱和支持的抗坏血酸作为电子供体是依赖于剩余的细胞色素b5的内容。它的结论是，细胞色素b5在肝微粒体中作为一个中间电子载体，通过还原当量从NADH，NADPH和抗坏血酸的氰化物敏感的因素，脂肪酸去饱和本身可能发生。从大鼠附睾脂肪组织制备的微粒体含有大量的细胞色素h，其在脂肪酸去饱和中起类似的作用。
On addition of NADPH to rat liver microsomes cytochrome b5 assumes a steady-state reduction level, based on a balance between its reduction by NADPH and its aut oxidation. Initiation of fatty acid desaturation by adding stearoyl-CoA(stearyl CoA) results in a rapid shift of the NADPH-supported steady state of the cytochrome in favor cf more oxidation, and this shift is intensified by partially inhibiting microsomal NADPH-specific flavoprotein by HgCl2 This suggests that increased utilization of reducing equivalents for desaturation is accompanied by a stimulation of reoxidation of cvtochrome b5. Actually, the magnitude of stearyl CoA-induced shift is roughly proportional to the fatty acid desaturation activity of the microsomes employed. Moreover, this shift is interfered with by cyanide which inhibits a terminal component (" cyanide-sensitive factor") of the desaturation system. Since the reduction of microsomal bound cytochrome b5 by NADH is much faster than the autoxidation of the cytochrome and the overall desaturation reaction, NADH causes complete reduction of cytochrome b5 and no change in the reduction level is observed on addition of stearyl CoA. However, when NADH-cytochrome b5 reductase is strongly inhibited by PCMS, stearyl CoA does lower the steady-state reduction level of cytochrome b5 in NADH-treated microsomes. Stearyl CoA also stimulates the oxidation of cytochrome b5 observable on exhaustion of the NADH added, and this stimulation is again prevented by cyanide. With microsomes from which cytochrome b5 has been removed to various extents by mild proteolytic digestion, the desaturation of stearyl CoA supported by ascorbate as electron donor is dependent on the content of remaining cytochrome b5. It is concluded that cytochrome b5 in liver microsomes acts as an intermediary electron carrier which passes reducing equivalents from NADH, NADPH and ascorbate to the cyanide-sensitive factor where fatty acid desaturation per se probably takes place. Micresomes prepared from rat epididymal adipose tissue contain a significant amount of cytochrome h, which plays a similar role in fatty acid desaturation.