Adrenodoxin reductase: Difference between revisions
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==Mitochondrial P450 systems== | ==Mitochondrial P450 systems== | ||
Mitochondrial P450 systems are expressed in cells that specialize in the biosynthesis and secretion of steroids. The reactions these systems catalyze include the first step in steroid hormone synthesis that is cleavage of the side chain of cholesterol producing pregnenolone, C11- hydroxylation of steroids producing glucocorticoids, C-18 hydroxylation of steroids leading to the synthesis of mineralocorticoids, and C-25 and C-27 hydroxylations of steroids in the pathways of bile acid and vitamin D synthesis.<ref name="HI-review" /> | |||
Mitochondrial P450 systems are composed of three proteins: | Mitochondrial P450 systems are composed of three proteins: | ||
* Adrenodoxin reductase | * Adrenodoxin reductase | ||
* Adrenodoxin, a [2Fe-2S] ferredoxin type iron-sulfur protein | * Adrenodoxin, a [2Fe-2S] ferredoxin type iron-sulfur protein | ||
* Mitochondrial P450 | * Mitochondrial P450 | ||
The first two electron transfer proteins are shared by all systems. Substrate and reaction specificity of the system is dependent on the type of P450. | |||
The reactions catalyzed by P450 type enzymes are called monooxygenation reactions because P450 catalyzes incorporation of only one atom of molecular O<sub>2</sub> into substrate (S) while reducing the second atom of O into H<sub>2</sub>O with the following stoichiometry: | The reactions catalyzed by P450 type enzymes are called monooxygenation reactions because P450 catalyzes incorporation of only one atom of molecular O<sub>2</sub> into substrate (S) while reducing the second atom of O into H<sub>2</sub>O with the following stoichiometry: | ||
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SH + O<sub>2</sub> + NAD(P)H + H<sup>+</sup> → ROH + H<sub>2</sub>O + NAD(P)<sup>+</sup> | SH + O<sub>2</sub> + NAD(P)H + H<sup>+</sup> → ROH + H<sub>2</sub>O + NAD(P)<sup>+</sup> | ||
In the mitochondrial P450 systems, the source of electrons is NADPH. The main function of AR in these systems is to accept two electrons from NADPH | In the mitochondrial P450 systems, the source of electrons is NADPH. The main function of AR in these systems is to accept two electrons from NADPH which are transferred to FAD with the following stoichiometry: | ||
NADPH + H<sup>+</sup> + FAD → NADP<sup>+</sup> + FADH<sub>2</sub> | |||
After this initial transfer, AR catalyzes transfer of electron from FADH<sub>2</sub> to adrenodoxin in two independent steps as adrenodoxin is a single electron acceptor. Reduced adrenodoxin in turn transfers its electron to mitochondrial P450 during the complex catalytic cycle of P450. | |||
Thus, the route of electron transfer in these systems is as follows: | |||
NADPH → AR → adrenodoxin → P450 | |||
==History== | ==History== | ||