The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

POR  -  P450 (cytochrome) oxidoreductase

Homo sapiens

Synonyms: CPR, CYPOR, FLJ26468, NADPH--cytochrome P450 reductase, P450R
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of POR


Psychiatry related information on POR


High impact information on POR

  • With these key residues as a guide, conclusive evidence is presented that the ferredoxin reductase structure is a prototype for the nicotinamide dinucleotide and FAD binding domains of the enzymes NADPH-cytochrome P450 reductase, NADPH-sulfite reductase, NADH-cytochrome b5 reductase, and NADH-nitrate reductase [8].
  • In 11 patients with decompensated cirrhosis and deteriorating renal function, the effect of the vasoconstrictor substance 8-ornithin vasopressin (ornipressin; POR 8; Sandoz, Basel, Switzerland) on renal function, hemodynamic parameters, and humoral mediators was studied [9].
  • The key enzyme of chlorophyll biosynthesis in higher plants, the light-dependent NADPH:protochlorophyllide oxidoreductase (POR, EC, is a nuclear-encoded plastid protein [10].
  • Our large survey of patients with ABS shows that individuals with an ABS-like phenotype and normal steroidogenesis have FGFR mutations, whereas those with ambiguous genitalia and disordered steroidogenesis should be recognized as having a distinct new disease: POR deficiency [11].
  • P450 oxidoreductase (POR) is the obligatory flavoprotein intermediate that transfers electrons from reduced nicotinamide adenine dinucleotide phosphate (NADPH) to all microsomal cytochrome P450 enzymes [11].

Chemical compound and disease context of POR

  • An homology model of protochlorophyllide reductase (POR) from Synechocystis sp. was constructed on a template from the tyrosine-dependent oxidoreductase family [12].
  • This advance in diagnostic ability has introduced the concept of conservative management for this condition.The authors describe the conservative management of nine cases of ectopic pregnancy using intrachorionic injection of either methotrexate alone or in combination with POR 8 [13].
  • Helicobacter pylori flavodoxin is the electronic acceptor of the pyruvate-oxidoreductase complex (POR) that catalyzes pyruvate oxidative decarboxilation [14].
  • Local infiltration of ornithine 8-vasopressin (POR 8) as a vasoconstrictive agent in surgical pelviscopy (applied to myoma enucleation, salpingotomy in cases of tubal pregnancy and peripheral salpingostomy) [15].
  • NADPH:protochlorophyllide oxidoreductase (POR) catalyzes hydrogen transfer from NADPH to protochlorophyllide (PChlide) in the course of chlorophyll biosynthesis in photosynthetic organisms and is involved in the regulation of the development of photosynthetic apparatus in higher plants, algae and cyanobacteria [16].

Biological context of POR

  • To address the molecular basis of CYPOR dysfunction in ABS patients, the soluble catalytic domain of human CYPOR was bacterially expressed [17].
  • A combination of calorimetry and stopped-flow spectrophotometry kinetics experiments showed that this linkage between coenzyme binding energetics and diffusional domain motion impinges directly on the molecular recognition of cytochrome c by CPR [18].
  • S. cerevisiae BWG1-7alpha transformed with the expression plasmids produced the respective proteins in the expected molecular sizes reactive with both anti-hCYP3A4 immunoglobulin (Ig) and anti-hCPR Ig [19].
  • BWG-CPR was further tested daily by the PCR amplification of hCPR of yeast genome, Western blot analysis, and the activity assay of hCPR of yeast microsome [19].
  • Cytochrome P450s (CYPs) hold a balance in studying pharmacokinetics, toxico-kinetics, drug metabolism, and drug-drug interactions, which require association with cytochrome P450 reductase (CPR) to achieve optimal activity [19].

Anatomical context of POR


Associations of POR with chemical compounds

  • Based on these findings, decreased FAD-binding affinity is proposed as the basis of the observed loss of CYPOR function in the Y459H and V492E POR mutations in ABS [17].
  • Thus, the final electron for reducing ferric biliverdin-iron chelate to release ferrous iron and biliverdin is apparently provided by the FMN of CPR [24].
  • This conclusion was supported by the observation that verdoheme dimethyl esters were accumulated in the reaction of the ferriprotoporphyrin IX dimethyl ester-rHO-1 complex with the wild-type CPR [24].
  • CYP4A4-catalyzed omega-hydroxylation of prostaglandin E(1) was supported by WT CYPOR but not by either of the ABS mutants [17].
  • Ferric biliverdin-iron chelate, generated with the FMN-depleted CPR, was converted to biliverdin by the addition of the wild-type CPR or desferrioxamine [24].

Physical interactions of POR

  • The Reactions of Heme- and Verdoheme-Heme Oxygenase-1 Complexes with FMN-depleted NADPH-cytochrome P450 Reductase: ELECTRONS REQUIRED FOR VERDOHEME OXIDATION CAN BE TRANSFERRED THROUGH A PATHWAY NOT INVOLVING FMN [24].
  • The concentration dependence of the rate of hydride transfer indicates that the second, noncatalytic NADPH-binding site present in wild-type CPR is retained in the mutant enzymes [25].
  • A chimera consisting of the nNOS heme domain and FMN binding subdomain and the CYPOR FAD binding subdomain catalyzed significantly increased rates of cytochrome c reduction in the absence of CaM and of NO synthesis in its presence [26].

Enzymatic interactions of POR

  • Human heme oxygenase-1 (hHO-1) catalyzes the NADPH-cytochrome P450 reductase-dependent oxidation of heme to biliverdin, CO, and free iron [27].
  • The chlorophyll biosynthesis enzyme protochlorophyllide reductase (POR) catalyzes the light-dependent reduction of protochlorophyllide (Pchlide) into chlorophyllide in the presence of NADPH [28].

Regulatory relationships of POR


Other interactions of POR


Analytical, diagnostic and therapeutic context of POR


  1. Crystallization and preliminary X-ray diffraction studies of human cytochrome P450 reductase. Zhao, Q., Smith, G., Modi, S., Paine, M., Wolf, R.C., Tew, D., Lian, L.Y., Primrose, W.U., Roberts, G.C., Driessen, H.P. J. Struct. Biol. (1996) [Pubmed]
  2. Establishment of ten strains of genetically engineered Salmonella typhimurium TA1538 each co-expressing a form of human cytochrome P450 with NADPH-cytochrome P450 reductase sensitive to various promutagens. Yamazaki, Y., Fujita, K., Nakayama, K., Suzuki, A., Nakamura, K., Yamazaki, H., Kamataki, T. Mutat. Res. (2004) [Pubmed]
  3. The reductive activation of the antitumor drug RH1 to its semiquinone free radical by NADPH cytochrome P450 reductase and by HCT116 human colon cancer cells. Hasinoff, B.B., Begleiter, A. Free Radic. Res. (2006) [Pubmed]
  4. The potential for CYP2D6 inhibition screening using a novel scintillation proximity assay-based approach. Delaporte, E., Slaughter, D.E., Egan, M.A., Gatto, G.J., Santos, A., Shelley, J., Price, E., Howells, L., Dean, D.C., Rodrigues, A.D. Journal of biomolecular screening : the official journal of the Society for Biomolecular Screening. (2001) [Pubmed]
  5. NADPH-cytochrome P-450 reductase is involved in flunitrazepam reductive metabolism in Hep G2 and Hep 3B cells. Peng, F.C., Chaing, H.H., Tang, S.H., Chen, P.C., Lu, S.C. J. Toxicol. Environ. Health Part A (2004) [Pubmed]
  6. Low fecal elastase-1 in type I diabetes mellitus. Icks, A., Haastert, B., Giani, G., Rathmann, W. Zeitschrift für Gastroenterologie. (2001) [Pubmed]
  7. Association between maternal panic disorders and pregnancy complications and delivery outcomes. Bánhidy, F., Acs, N., Puhó, E., Czeizel, A.E. Eur. J. Obstet. Gynecol. Reprod. Biol. (2006) [Pubmed]
  8. Atomic structure of ferredoxin-NADP+ reductase: prototype for a structurally novel flavoenzyme family. Karplus, P.A., Daniels, M.J., Herriott, J.R. Science (1991) [Pubmed]
  9. Ornipressin in the treatment of functional renal failure in decompensated liver cirrhosis. Effects on renal hemodynamics and atrial natriuretic factor. Lenz, K., Hörtnagl, H., Druml, W., Reither, H., Schmid, R., Schneeweiss, B., Laggner, A., Grimm, G., Gerbes, A.L. Gastroenterology (1991) [Pubmed]
  10. Enzymatic product formation impairs both the chloroplast receptor-binding function as well as translocation competence of the NADPH: protochlorophyllide oxidoreductase, a nuclear-encoded plastid precursor protein. Reinbothe, S., Reinbothe, C., Runge, S., Apel, K. J. Cell Biol. (1995) [Pubmed]
  11. Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Huang, N., Pandey, A.V., Agrawal, V., Reardon, W., Lapunzina, P.D., Mowat, D., Jabs, E.W., Van Vliet, G., Sack, J., Flück, C.E., Miller, W.L. Am. J. Hum. Genet. (2005) [Pubmed]
  12. Protochlorophyllide oxidoreductase: a homology model examined by site-directed mutagenesis. Townley, H.E., Sessions, R.B., Clarke, A.R., Dafforn, T.R., Griffiths, W.T. Proteins (2001) [Pubmed]
  13. Ectopic pregnancy treatment using pelviscopic or vaginosonographically-guided intrachorionic injection of methotrexate and POR 8. Popp, L.W., Mettler, L., Weisner, D., Mecke, H., Freys, I., Semm, K. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. (1991) [Pubmed]
  14. Towards a new therapeutic target: Helicobacter pylori flavodoxin. Cremades, N., Bueno, M., Toja, M., Sancho, J. Biophys. Chem. (2005) [Pubmed]
  15. Local infiltration of ornithine 8-vasopressin (POR 8) as a vasoconstrictive agent in surgical pelviscopy (applied to myoma enucleation, salpingotomy in cases of tubal pregnancy and peripheral salpingostomy). Semm, K., Mettler, L. Endoscopy. (1988) [Pubmed]
  16. POR structural domains important for the enzyme activity in R. capsulatus complementation system. Lebedev, N., Timko, M.P. Photosyn. Res. (2002) [Pubmed]
  17. Diminished FAD Binding in the Y459H and V492E Antley-Bixler Syndrome Mutants of Human Cytochrome P450 Reductase. Marohnic, C.C., Panda, S.P., Mart??sek, P., Masters, B.S. J. Biol. Chem. (2006) [Pubmed]
  18. Global effects of the energetics of coenzyme binding: NADPH controls the protein interaction properties of human cytochrome P450 reductase. Grunau, A., Paine, M.J., Ladbury, J.E., Gutierrez, A. Biochemistry (2006) [Pubmed]
  19. Establishment of a yeast system that stably expresses human cytochrome P450 reductase: application for the study of drug metabolism of cytochrome P450s in vitro. Cheng, J., Wan, D.F., Gu, J.R., Gong, Y., Yang, S.L., Hao, D.C., Yang, L. Protein Expr. Purif. (2006) [Pubmed]
  20. Abnormal microsomal detoxification implicated in Fanconi anemia group C by interaction of the FAC protein with NADPH cytochrome P450 reductase. Kruyt, F.A., Hoshino, T., Liu, J.M., Joseph, P., Jaiswal, A.K., Youssoufian, H. Blood (1998) [Pubmed]
  21. NADPH-cytochrome P-450 reductase in the plasma membrane modulates the activation of hypoxia-inducible factor 1. Osada, M., Imaoka, S., Sugimoto, T., Hiroi, T., Funae, Y. J. Biol. Chem. (2002) [Pubmed]
  22. Organization of multiple cytochrome P450s with NADPH-cytochrome P450 reductase in membranes. Backes, W.L., Kelley, R.W. Pharmacol. Ther. (2003) [Pubmed]
  23. Expression of DT-diaphorase and cytochrome P450 reductase correlates with mitomycin C activity in human bladder tumors. Gan, Y., Mo, Y., Kalns, J.E., Lu, J., Danenberg, K., Danenberg, P., Wientjes, M.G., Au, J.L. Clin. Cancer Res. (2001) [Pubmed]
  24. The Reactions of Heme- and Verdoheme-Heme Oxygenase-1 Complexes with FMN-depleted NADPH-cytochrome P450 Reductase: ELECTRONS REQUIRED FOR VERDOHEME OXIDATION CAN BE TRANSFERRED THROUGH A PATHWAY NOT INVOLVING FMN. Higashimoto, Y., Sato, H., Sakamoto, H., Takahashi, K., Palmer, G., Noguchi, M. J. Biol. Chem. (2006) [Pubmed]
  25. Trp-676 facilitates nicotinamide coenzyme exchange in the reductive half-reaction of human cytochrome P450 reductase: properties of the soluble W676H and W676A mutant reductases. Gutierrez, A., Doehr, O., Paine, M., Wolf, C.R., Scrutton, N.S., Roberts, G.C. Biochemistry (2000) [Pubmed]
  26. Chimeric enzymes of cytochrome P450 oxidoreductase and neuronal nitric-oxide synthase reductase domain reveal structural and functional differences. Roman, L.J., McLain, J., Masters, B.S. J. Biol. Chem. (2003) [Pubmed]
  27. The binding sites on human heme oxygenase-1 for cytochrome p450 reductase and biliverdin reductase. Wang, J., de Montellano, P.R. J. Biol. Chem. (2003) [Pubmed]
  28. Enzymology below 200 K: the kinetics and thermodynamics of the photochemistry catalyzed by protochlorophyllide oxidoreductase. Heyes, D.J., Ruban, A.V., Wilks, H.M., Hunter, C.N. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  29. Tyr275 and Lys279 stabilize NADPH within the catalytic site of NADPH:protochlorophyllide oxidoreductase and are involved in the formation of the enzyme photoactive state. Lebedev, N., Karginova, O., McIvor, W., Timko, M.P. Biochemistry (2001) [Pubmed]
  30. Expression of cytochrome P450 3A7 in Escherichia coli: effects of 5' modification and catalytic characterization of recombinant enzyme expressed in bicistronic format with NADPH-cytochrome P450 reductase. Gillam, E.M., Wunsch, R.M., Ueng, Y.F., Shimada, T., Reilly, P.E., Kamataki, T., Guengerich, F.P. Arch. Biochem. Biophys. (1997) [Pubmed]
  31. CYP3A4 expressed by insect cells infected with a recombinant baculovirus containing both CYP3A4 and human NADPH-cytochrome P450 reductase is catalytically similar to human liver microsomal CYP3A4. Lee, C.A., Kadwell, S.H., Kost, T.A., Serabjit-Singh, C.J. Arch. Biochem. Biophys. (1995) [Pubmed]
  32. Identification and functional characterization of novel CYP2J2 variants: G312R variant causes loss of enzyme catalytic activity. Lee, S.S., Jeong, H.E., Liu, K.H., Ryu, J.Y., Moon, T., Yoon, C.N., Oh, S.J., Yun, C.H., Shin, J.G. Pharmacogenet. Genomics (2005) [Pubmed]
  33. Stable expression and coexpression of human cytochrome P450 oxidoreductase and cytochrome P450 1A2 in V79 Chinese hamster cells: sensitivity to quinones and biotransformation of 7-alkoxyresorufins and triazines. Schmalix, W.A., Lang, D., Schneider, A., Bocker, R., Greim, H., Doehmer, J. Drug Metab. Dispos. (1996) [Pubmed]
  34. Adrenodoxin supports reactions catalyzed by microsomal steroidogenic cytochrome P450s. Pechurskaya, T.A., Harnastai, I.N., Grabovec, I.P., Gilep, A.A., Usanov, S.A. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  35. Metabolic activation of N-alkylnitrosamines in genetically engineered Salmonella typhimurium expressing CYP2E1 or CYP2A6 together with human NADPH-cytochrome P450 reductase. Kushida, H., Fujita, K., Suzuki, A., Yamada, M., Endo, T., Nohmi, T., Kamataki, T. Carcinogenesis (2000) [Pubmed]
  36. Coexpression of mammalian cytochrome P450 and reductase in Escherichia coli. Dong, J., Porter, T.D. Arch. Biochem. Biophys. (1996) [Pubmed]
  37. Effects of chronic exposure to cadmium on renal cytochrome P450-dependent monooxygenase system in rats. Plewka, A., Plewka, D., Nowaczyk, G., Brzóska, M.M., Kamiński, M., Moniuszko-Jakoniuk, J. Arch. Toxicol. (2004) [Pubmed]
  38. The First Catalytic Step of the Light-driven Enzyme Protochlorophyllide Oxidoreductase Proceeds via a Charge Transfer Complex. Heyes, D.J., Heathcote, P., Rigby, S.E., Palacios, M.A., van Grondelle, R., Hunter, C.N. J. Biol. Chem. (2006) [Pubmed]
WikiGenes - Universities