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Gene Review

CPOX  -  coproporphyrinogen oxidase

Homo sapiens

Synonyms: COX, CPO, CPX, Coprogen oxidase, Coproporphyrinogenase, ...
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Disease relevance of CPOX


Psychiatry related information on CPOX

  • For both the control group and the left HCP group, a linear increase in reaction time as a function of angle of rotation was found [6].
  • CPX can identify patients with severe PR and RV dysfunction and may be useful to guide the pulmonary valve replacement decision-making process [7].
  • DESIGN: We evaluated the effects of diagnosis (CLP, CPO, or no diagnosis) and age (3, 12, and 24 months) on facial attractiveness ratings derived from a modified Q-sort method [8].

High impact information on CPOX


Chemical compound and disease context of CPOX


Biological context of CPOX

  • Coproporphyrinogen oxidase (CPOX), the sixth enzyme in the heme-biosynthetic pathway, catalyzes oxidative decarboxylation of coproporphyrinogen to protoporphyrinogen and is located in the intermembrane space of mitochondria [1].
  • Conversely, the transfection of antisense oligonucleotide to human CPOX mRNA into untreated and TGF beta 1-treated K562 cells led to a decrease in heme production compared with sense oligonucleotide-transfected cells [1].
  • We then analysed the available single-nucleotide polymorphisms (SNPs) present at high frequencies in the general population and spreading throughout the FECH, HMBS, PPOX and the CPO genes in four case-control association studies [19].
  • For HC, the CPO mRNA determinations strongly suggest that normal CPO alleles with low-expression are present, but whether this low-expression of the wild-type allele could modulate the penetrance of a CPO gene defect in HC families remains to be ascertained [19].
  • The biogenesis of the inner mitochondrial membrane enzyme cytochrome c oxidase (COX) is a complex process that requires the actions of ancillary proteins, collectively called assembly factors [20].

Anatomical context of CPOX

  • These increases in the transfected cells were twice those in control cells, indicating that overexpression of CPOX enhanced induction of the differentiation of K562 cells mediated by TGF beta 1 or ALA [1].
  • The A ring isomer coproporphyrinogen-IV (C-IV) has previously been shown to be a substrate for copro'gen oxidase derived from avian erythrocytes [21].
  • Immunostaining with specific antibodies failed to detect the presence of several smaller subunits in the complex lacking COX III, in spite of the demonstration that these subunits were present in the crude mitochondrial fraction of patient's cultured fibroblasts [22].
  • CONCLUSIONS: In skeletal muscle, HIV+NRTI+ had a reduced mt/n DNA ratio, more frequent mtDNA deletions and possibly more COX-deficient muscle fibres than HIV-negative controls [23].
  • The COX III gene mutation resulted in a severe respiratory chain defect in all mutant cell lines [24].

Associations of CPOX with chemical compounds

  • These findings indicate that the G265-->A transition, involving the highly conserved glycine residue at the 89th position, is responsible for the CPO defect in the patient and accounts for the partial deficiency of CPO activity in this pedigree [4].
  • Patients with current use of didanosine (ddl) had more frequent mtDNA deletions and COX-deficient fibres than HIV+NRTI+ not on current treatment with ddl [23].
  • Cells homoplasmic for the mutation had no detectable COX activity or respiratory ATP synthesis, and required uridine and pyruvate supplementation for growth, a phenotype similar to rho(0) cells [24].
  • The Cu(2+) chelating action of HCys and impairement of COX activity represent novel mechanisms of HCys neurotoxicity, which might be preventable by supplementation of Cu(2+) [15].
  • We hypothesize that ethanol withdrawal (EW) impairs the activity of COX and estrogen deprivation exacerbates this problem [25].

Regulatory relationships of CPOX

  • The discovery that IL-10 can inhibit the production of coproporphyrinogen oxidase (an enzyme involved in the synthesis of heme) may shed some lights on the mechanisms of anaemia induced by IL-10 [26].

Other interactions of CPOX


Analytical, diagnostic and therapeutic context of CPOX

  • Molecular cloning, sequencing and expression of the defective gene for coproporphyrinogen oxidase (CPO) in a patient with HCP were carried out [4].
  • Previously, based upon metal analysis and site-directed mutagenesis of purified recombinant enzyme, it has been suggested that CPO contains and requires copper for activity (Kohno, H., Furukawa, T., Tokunaga, R., Taketani, S., and Yoshinaga, T. (1996) Biochim. Biophys. Acta 1292, 156-162) [29].
  • We investigated the molecular basis of hereditary coproporphyria in three unrelated patients, amplifying each exon of the coproporphyrinogen oxidase gene and performing heteroduplex analysis to look for mutations [30].
  • Western blot analysis of two-dimensional blue-native electrophoresis showed a reduction of specific crossreacting material and the accumulation of early-assembly intermediates of COX, whereas the fully assembled complex was absent [22].
  • Because the iron concentration in the cell culture medium was determined to be 16 micromol/L, DFX but not CPX function can be explained by complete chelation of medium iron [31].


  1. Expression of coproporphyrinogen oxidase and synthesis of hemoglobin in human erythroleukemia K562 cells. Taketani, S., Furukawa, T., Furuyama, K. Eur. J. Biochem. (2001) [Pubmed]
  2. Molecular characterization of porphyrias in Italy: a diagnostic flow-chart. Martinez di Montemuros, F., Di Pierro, E., Patti, E., Tavazzi, D., Danielli, M.G., Biolcati, G., Rocchi, E., Cappellini, M.D. Cell. Mol. Biol. (Noisy-le-grand) (2002) [Pubmed]
  3. Mutant and wild-type alpha-synuclein interact with mitochondrial cytochrome C oxidase. Elkon, H., Don, J., Melamed, E., Ziv, I., Shirvan, A., Offen, D. J. Mol. Neurosci. (2002) [Pubmed]
  4. Characterization and expression of cDNA encoding coproporphyrinogen oxidase from a patient with hereditary coproporphyria. Fujita, H., Kondo, M., Taketani, S., Nomura, N., Furuyama, K., Akagi, R., Nagai, T., Terajima, M., Galbraith, R.A., Sassa, S. Hum. Mol. Genet. (1994) [Pubmed]
  5. A molecular defect in coproporphyrinogen oxidase gene causing harderoporphyria, a variant form of hereditary coproporphyria. Lamoril, J., Martasek, P., Deybach, J.C., Da Silva, V., Grandchamp, B., Nordmann, Y. Hum. Mol. Genet. (1995) [Pubmed]
  6. Impaired motor imagery in right hemiparetic cerebral palsy. Mutsaarts, M., Steenbergen, B., Bekkering, H. Neuropsychologia (2007) [Pubmed]
  7. Impact of pulmonary regurgitation and right ventricular dysfunction on oxygen uptake recovery kinetics in repaired tetralogy of Fallot. Giardini, A., Specchia, S., Coutsoumbas, G., Donti, A., Formigari, R., Fattori, R., Oppido, G., Gargiulo, G., Picchio, F.M. Eur. J. Heart Fail. (2006) [Pubmed]
  8. Facial appearance and attachment in infants with orofacial clefts: a replication. Coy, K., Speltz, M.L., Jones, K. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. (2002) [Pubmed]
  9. Decreased activity of hepatic uroporphyrinogen decarboxylase in sporadic porphyria cutanea tarda. Elder, G.H., Lee, G.B., Tovey, J.A. N. Engl. J. Med. (1978) [Pubmed]
  10. COX-3: just another COX or the solitary elusive target of paracetamol? Schwab, J.M., Schluesener, H.J., Laufer, S. Lancet (2003) [Pubmed]
  11. Coproporphyrinogen-oxidase deficiency in hereditary coproporphyria. Nordmann, Y., Grandchamp, B., Phung, N., de Verneuil, H., Grelier, M., Neiré, J. Lancet (1977) [Pubmed]
  12. The primary enzyme defect in hereditary coproporphyria. Elder, G.H., Evans, J.O., Thomas, N. Lancet (1976) [Pubmed]
  13. Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia. Longley, M.J., Clark, S., Yu Wai Man, C., Hudson, G., Durham, S.E., Taylor, R.W., Nightingale, S., Turnbull, D.M., Copeland, W.C., Chinnery, P.F. Am. J. Hum. Genet. (2006) [Pubmed]
  14. Homozygous hereditary coproporphyria caused by an arginine to tryptophane substitution in coproporphyrinogen oxidase and common intragenic polymorphisms. Martasek, P., Nordmann, Y., Grandchamp, B. Hum. Mol. Genet. (1994) [Pubmed]
  15. Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells. Linnebank, M., Lutz, H., Jarre, E., Vielhaber, S., Noelker, C., Struys, E., Jakobs, C., Klockgether, T., Evert, B.O., Kunz, W.S., Wüllner, U. Neurobiol. Dis. (2006) [Pubmed]
  16. 8-cyclopentyl-1,3-dipropylxanthine and other xanthines differentially bind to the wild-type and delta F508 first nucleotide binding fold (NBF-1) domains of the cystic fibrosis transmembrane conductance regulator. Cohen, B.E., Lee, G., Jacobson, K.A., Kim, Y.C., Huang, Z., Sorscher, E.J., Pollard, H.B. Biochemistry (1997) [Pubmed]
  17. Activation of deltaF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX. Andersson, C., Roomans, G.M. Eur. Respir. J. (2000) [Pubmed]
  18. Outcome of subjects with idiopathic pulmonary fibrosis who fail corticosteroid therapy. Implications for further studies. Dayton, C.S., Schwartz, D.A., Helmers, R.A., Pueringer, R.J., Gilbert, S.R., Merchant, R.K., Hunninghake, G.W. Chest (1993) [Pubmed]
  19. Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias. Gouya, L., Puy, H., Robreau, A.M., Lyoumi, S., Lamoril, J., Da Silva, V., Grandchamp, B., Deybach, J.C. Hum. Genet. (2004) [Pubmed]
  20. Defects in cytochrome oxidase assembly in humans: lessons from yeast. Zee, J.M., Glerum, D.M. Biochem. Cell Biol. (2006) [Pubmed]
  21. Kinetic evaluation of human cloned coproporphyrinogen oxidase using a ring isomer of the natural substrate. Cooper, C.L., Lash, T.D., Jones, M.A. Med. Sci. Monit. (2005) [Pubmed]
  22. A novel frameshift mutation of the mtDNA COIII gene leads to impaired assembly of cytochrome c oxidase in a patient affected by Leigh-like syndrome. Tiranti, V., Corona, P., Greco, M., Taanman, J.W., Carrara, F., Lamantea, E., Nijtmans, L., Uziel, G., Zeviani, M. Hum. Mol. Genet. (2000) [Pubmed]
  23. Mitochondrial (mt)DNA changes in tissue may not be reflected by depletion of mtDNA in peripheral blood mononuclear cells in HIV-infected patients. Maagaard, A., Holberg-Petersen, M., Kollberg, G., Oldfors, A., Sandvik, L., Bruun, J.N. Antivir. Ther. (Lond.) (2006) [Pubmed]
  24. A pathogenic 15-base pair deletion in mitochondrial DNA-encoded cytochrome c oxidase subunit III results in the absence of functional cytochrome c oxidase. Hoffbuhr, K.C., Davidson, E., Filiano, B.A., Davidson, M., Kennaway, N.G., King, M.P. J. Biol. Chem. (2000) [Pubmed]
  25. Ethanol withdrawal posttranslationally decreases the activity of cytochrome c oxidase in an estrogen reversible manner. Jung, M.E., Agarwal, R., Simpkins, J.W. Neurosci. Lett. (2007) [Pubmed]
  26. Adherence modifies the regulation of gene expression induced by interleukin-10. Petit-Bertron, A.F., Pedron, T., Gross, U., Coppée, J.Y., Sansonetti, P.J., Cavaillon, J.M., Adib-Conquy, M. Cytokine (2005) [Pubmed]
  27. Congenital erythropoietic porphyria: clinical, biochemical, and enzymatic profile of a severely affected infant. Huang, J.L., Zaider, E., Roth, P., Garcia, O., Pollack, S., Poh-Fitzpatrick, M.B. J. Am. Acad. Dermatol. (1996) [Pubmed]
  28. Coexistence of hereditary coproporphyria and epilepsy: coproporphyrinogen oxidase deficiency in liver and kidney. Doss, M., von Tiepermann, R., Pflüger, K.H. J. Neurol. (1981) [Pubmed]
  29. Human coproporphyrinogen oxidase is not a metalloprotein. Medlock, A.E., Dailey, H.A. J. Biol. Chem. (1996) [Pubmed]
  30. Hereditary coproporphyria: exon screening by heteroduplex analysis detects three novel mutations in the coproporphyrinogen oxidase gene. Schreiber, W.E., Zhang, X., Senz, J., Jamani, A. Hum. Mutat. (1997) [Pubmed]
  31. Epolones induce erythropoietin expression via hypoxia-inducible factor-1 alpha activation. Wanner, R.M., Spielmann, P., Stroka, D.M., Camenisch, G., Camenisch, I., Scheid, A., Houck, D.R., Bauer, C., Gassmann, M., Wenger, R.H. Blood (2000) [Pubmed]
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