ArticleDrug metabolism and disposition: the biological fate of chemicals2010
Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Structural context of NADPH-cytochrome P450 reductase mutations that alter cytochrome P450 1A2 substrate regioselectivity.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- A Novel POR G88S Mutation Causes Severe PORD and Establishes a Critical Pharmacogenomic Risk Profile.The Journal of clinical endocrinology and metabolism · 2026Article
- Single Mutations in Cytochrome P450 Oxidoreductase Can Alter the Specificity of Human Cytochrome P450 1A2-Mediated Caffeine Metabolism.Biomolecules · 2023Article
- Interaction Modes of Microsomal Cytochrome P450s with Its Reductase and the Role of Substrate Binding.International journal of molecular sciences · 2020Article
- The Role of the FMN-Domain of Human Cytochrome P450 Oxidoreductase in Its Promiscuous Interactions With Structurally Diverse Redox Partners.Frontiers in pharmacology · 2020Article
- Variability in Loss of Multiple Enzyme Activities Due to the Human Genetic Variation P284T Located in the Flexible Hinge Region of NADPH Cytochrome P450 Oxidoreductase.Frontiers in pharmacology · 2019Article
- Probing the Role of the Hinge Segment of Cytochrome P450 Oxidoreductase in the Interaction with Cytochrome P450.International journal of molecular sciences · 2018Article
- Altered CYP19A1 and CYP3A4 Activities Due to Mutations A115V, T142A, Q153R and P284L in the Human P450 Oxidoreductase.Frontiers in pharmacology · 2017Article
- The Hinge Segment of Human NADPH-Cytochrome P450 Reductase in Conformational Switching: The Critical Role of Ionic Strength.Frontiers in pharmacology · 2017Article
- Instability of the Human Cytochrome P450 Reductase A287P Variant Is the Major Contributor to Its Antley-Bixler Syndrome-like Phenotype.The Journal of biological chemistry · 2016Article
- Article
- Electron transfer by human wild-type and A287P mutant P450 oxidoreductase assessed by transient kinetics: functional basis of P450 oxidoreductase deficiency.The Biochemical journal · 2015Article
- Role of protein-protein interactions in cytochrome P450-mediated drug metabolism and toxicity.Chemical research in toxicology · 2014Review
- Pharmacogenomics of human P450 oxidoreductase.Frontiers in pharmacology · 2014Review
- Article
- Intra- and inter-molecular effects of a conserved arginine residue of neuronal and inducible nitric oxide synthases on FMN and calmodulin binding.Archives of biochemistry and biophysics · 2013Article
- NADPH-cytochrome P450 oxidoreductase: prototypic member of the diflavin reductase family.Archives of biochemistry and biophysics · 2012Review
- Potential biological functions of cytochrome P450 reductase-dependent enzymes in small intestine: novel link to expression of major histocompatibility complex class II genes.The Journal of biological chemistry · 2012Article
- Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations.Pharmacogenomics · 2012Article
- Altered human CYP3A4 activity caused by Antley-Bixler syndrome-related variants of NADPH-cytochrome P450 oxidoreductase measured in a robust in vitro system.Drug metabolism and disposition: the biological fate of chemicals · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with congenital adrenal hyperplasia, exhibiting combined CYP17 and CYP21 deficiency, were shown by Arlt et al. (2004) to harbor a 541T-->G mutation in exon 5 of POR (encoding NADPH-cytochrome P450 reductase, CYPOR), which resulted in a Y181D substitution that obliterated electron transfer capacity. Using bacterial expression models, we examined catalytic and physical properties of the human CYPOR Y181D variant. As purified, Y181D lacked flavin mononucleotide (FMN) and NADPH-cytochrome c reductase (NCR) activity but retained normal flavin adenine dinucleotide binding and NADPH utilization. Titration of the purified protein with FMN restored 64 of wild-type (WT) NCR activity in Y181D with an activation constant of approximately 2 microM. As determined by FMN fluorescence quenching, Y181D had K(d)(FMN) = 7.3 microM. Biplasmid coexpression of CYPOR and CYP1A2, at the physiological ratio of approximately 1:10 in the engineered MK_1A2_POR Escherichia coli strain, showed the compromised capacity of Y181D to support CYP1A2-catalyzed metabolism of the procarcinogens 2-aminoanthracene, 2-amino-3-methylimidazo(4,5-f)quinoline, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Isolated MK1A2_POR membranes confirmed FMN stimulation of Y181D NCR activity with a 1.6 microM activation constant. CYP1A2 ethoxyresorufin-O-dealkylase activity of the MK1A2_POR(Y181D) membranes, undetectable in the absence of added FMN, increased to 37% of MK1A2_POR(WT) membranes with a 1.2 microM FMN activation constant. Therefore, we conclude that compromised FMN binding is the specific molecular defect causing POR deficiency in patients with Y181D mutation and that this defect, in large part, can be overcome in vitro by FMN addition.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.