Sandbox 177: Difference between revisions
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NADPH-cytochrome P450 oxidoreductase (CYPOR) is a ~78kDa, multidomain flavoprotein. <ref name="5TSON">PMID:19171935</ref> Containing three co-factors, FMN, FAD and NADPH, CYPOR is the archetype for the mammalian diflavin-containing enzyme family.<ref name="5TSON"/> | NADPH-cytochrome P450 oxidoreductase (CYPOR) is a ~78kDa, multidomain flavoprotein. <ref name="5TSON">PMID:19171935</ref> Containing three co-factors, FMN, FAD and NADPH, CYPOR is the archetype for the mammalian diflavin-containing enzyme family.<ref name="5TSON"/> | ||
Horecker first identified this protein in 1950 as NADPH-specific cytochrome c reductase, based on his assumption that it was the redox partner for cytochrome c, found in the mitochondria ( | Horecker first identified this protein in 1950 as NADPH-specific cytochrome c reductase, based on his assumption that it was the redox partner for cytochrome c, found in the mitochondria.<ref name="1TSON">Horecker BL. Triphosphopyridine nucleotide-cytochrome ''c'' reductase in liver. J Biol Chem 1950 April 1;183(2):593-605</ref> However, studies in the 1960s and later showed that its main function is actually as the redox partner for cytochrome P450 in microsomal electron transport chains, thus the name change (4).<ref name="5TSON"/> | ||
Regulation of this protein, which is found all tissues to some extent, is largely at the transcriptional level | Regulation of this protein, which is found all tissues to some extent, is largely at the transcriptional level.<ref name="3cTSON">PMID:11306680</ref> The thyroid hormone T3 in most cases, while adrenocorticotrophic hormone acts as a regulator in a few specific cases.<ref name="3aTSON">PMID:2495435</ref><ref name="3bTSON">PMID:1737785</ref> | ||
==Structure== | ==Structure== | ||
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''In vivo'' CYPOR is believe to alternate between a one and a three electron reduced form. While the 1 electron form is fairly stable, forming a neutral blue semiquinone, it is the hydroquinone, or 3 electron form, that is able to donate electrons to the desired redox partners. | ''In vivo'' CYPOR is believe to alternate between a one and a three electron reduced form. While the 1 electron form is fairly stable, forming a neutral blue semiquinone, it is the hydroquinone, or 3 electron form, that is able to donate electrons to the desired redox partners. | ||
As part of the microsomal electron transport system, CYPOR moves electrons from NADPH -> FAD -> FMN -> cytochrome P450. Specifically a hydride anion is moved from NADPH to the FAD. The two electrons are then individually passed to FMN, in a process that is believed to be conformationally gated, before being passed on to cytochrome P450, again one at a time.<ref name="5TSON"/> This reduction of cytochrome P450 allows it to function in biosynthesis and biodegradation pathways of a variety of endogenous and foreign hydrophobic substrates, including drugs and steroids ( | As part of the microsomal electron transport system, CYPOR moves electrons from NADPH -> FAD -> FMN -> cytochrome P450. Specifically a hydride anion is moved from NADPH to the FAD. The two electrons are then individually passed to FMN, in a process that is believed to be conformationally gated, before being passed on to cytochrome P450, again one at a time.<ref name="5TSON"/> This reduction of cytochrome P450 allows it to function in biosynthesis and biodegradation pathways of a variety of endogenous and foreign hydrophobic substrates, including drugs and steroids (6).<ref name="5TSON"/><ref name="2TSON">PMID:7743131</ref> | ||
Cytochrome b5, cytochrome c and heme oxygenase can also receive electrons from CYPOR.<ref name="5TSON"/> In these cases CYPOR is functioning in the heme degradation pathway, or with monooxygenase and/or 7-dehydrocholesterol reductase in sterol synthesis.<ref name="5TSON"/> | Cytochrome b5, cytochrome c and heme oxygenase can also receive electrons from CYPOR.<ref name="5TSON"/> In these cases CYPOR is functioning in the heme degradation pathway, or with monooxygenase and/or 7-dehydrocholesterol reductase in sterol synthesis.<ref name="5TSON"/> | ||
