Department of Biochemistry, University of Stellenbosch, Stellenbosch 7602, South Africa.
Mol Cell Endocrinol. 2013 May 22;371(1-2):87-99. doi: 10.1016/j.mce.2012.11.020. Epub 2012 Dec 7.
Cytochrome b(5) (cyt-b(5)) is essential for the regulation of steroidogenesis and as such has been implicated in a number of clinical conditions. It is well documented that this small hemoprotein augments the 17,20-lyase activity of cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1). Studies have revealed that this augmentation is accomplished by cyt-b(5) enhancing the interaction between cytochrome P450 reductase (POR) and CYP17A1. In this paper we present evidence that cyt-b(5) induces a conformational change in CYP17A1, in addition to facilitating the interaction between CYP17A1 and POR. We also review the recently published finding that cyt-b(5) allosterically augments the activity of 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3βHSD), a non cytochrome P450 enzyme, by increasing the enzymes affinity for its cofactor, NAD(+). The physiological importance of this finding, in terms of understanding adrenal androstenedione production, is examined. Finally, evidence that cyt-b(5) is able to form homomeric complexes in living cells is presented and discussed.
细胞色素 b(5)（cyt-b(5)）对于类固醇生成的调节至关重要，因此与许多临床情况有关。有大量文献记载，这种小的血红素蛋白可增强细胞色素 P450 17α-羟化酶/17,20-裂合酶（CYP17A1）的 17,20-裂合酶活性。研究表明，这种增强作用是通过 cyt-b(5)增强细胞色素 P450 还原酶（POR）与 CYP17A1 之间的相互作用来实现的。在本文中，我们提供了证据表明 cyt-b(5)除了促进 CYP17A1 与 POR 之间的相互作用外，还诱导 CYP17A1 发生构象变化。我们还回顾了最近发表的一项发现，即 cyt-b(5)通过增加酶对其辅因子 NAD(+)的亲和力，变构增强非细胞色素 P450 酶 3β-羟甾脱氢酶/Δ(5)-Δ(4)异构酶（3βHSD）的活性。该发现对于理解肾上腺雄烯二酮的产生具有重要的生理意义。最后，提出并讨论了 cyt-b(5)能够在活细胞中形成同型复合物的证据。
