PPOX
| Protoporfirinogen-oksidaza | |
|---|---|
 | |
| Identifikatori | |
| Simbol | PPOX |
| CAS broj | |
Protoporfirinogen-oksidaza ili protoks jest enzim koji je kod ljudi kodiran genom PPOX sa hromosoma 1.[5][6][7]
Protoporfirinogen-oksidaza odgovorna je za sedmi korak u biosintezi protoporfirina IX. Ovaj porfirin je prekursor hemoglobina, nositelja kisika kod životinja i hlorofila, u biljkama. Enzim katalizira dehidrogenaciju (uklanjanje vodikovih atoma) protoporfirinogena IX (proizvod šestog koraka u proizvodnji hema), da bi se formirao protoporfirin IX. Jedan dodatni enzim mora modificirati protoporfirin IX, prije nego što postane hem. Inhibicija ovog enzima je strategija koja se koristi u određenim herbicidima.
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 477 aminokiselina, a molekulska težina 50.765 Da.[8]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MGRTVVVLGG | GISGLAASYH | LSRAPCPPKV | VLVESSERLG | GWIRSVRGPN | ||||
| GAIFELGPRG | IRPAGALGAR | TLLLVSELGL | DSEVLPVRGD | HPAAQNRFLY | ||||
| VGGALHALPT | GLRGLLRPSP | PFSKPLFWAG | LRELTKPRGK | EPDETVHSFA | ||||
| QRRLGPEVAS | LAMDSLCRGV | FAGNSRELSI | RSCFPSLFQA | EQTHRSILLG | ||||
| LLLGAGRTPQ | PDSALIRQAL | AERWSQWSLR | GGLEMLPQAL | ETHLTSRGVS | ||||
| VLRGQPVCGL | SLQAEGRWKV | SLRDSSLEAD | HVISAIPASV | LSELLPAEAA | ||||
| PLARALSAIT | AVSVAVVNLQ | YQGAHLPVQG | FGHLVPSSED | PGVLGIVYDS | ||||
| VAFPEQDGSP | PGLRVTVMLG | GSWLQTLEAS | GCVLSQELFQ | QRAQEAAATQ | ||||
| LGLKEMPSHC | LVHLHKNCIP | QYTLGHWQKL | ESARQFLTAH | RLPLTLAGAS | ||||
| YEGVAVNDCI | ESGRQAAVSV | LGTEPNS |
Gen
[uredi | uredi izvor]Gen PPOX nalazi se na dugom (q) kraku hromosoma 1, na poziciji 22, od bazmog pata 157,949.266 do baznog para 157,954.082.
Funkcija
[uredi | uredi izvor]Ovaj gen kodira pretposljednji enzim biosinteze hema, koji katalizuje 6-elektronsku oksidaciju protoporfirinogena IX da bi se formirao protoporfirin IX. Ovaj protein je flavoprotein, povezan sa vanjskom površinom unutrašnje mitohondrijalne membrane.[7]
Biosintetski put hema
[uredi | uredi izvor]Sljedeći geni kodiraju enzime koji kataliziraju različite korake na biosintetskom putu hema:
- ALAD: aminolevulinat, delta-, dehidrataza
- ALAS1: aminolevulinat, delta-, sintaza 1
- ALAS2: aminolevulinat, delta-, sintaza 2 (sideroblastna/hipohromna anemija)
- CPOX: koproporfirinogen oksidaza
- FECH: ferokelataza (protoporfirija)
- HMBS: hidroksimetilbilan sintaza
- PPOX: protoporfirinogen oksidaza
- UROD: uroporfirinogen dekarboksilaza
- UROS: uroporfirinogen III sintaza (kongenitalna eritropoetska porfirija)
Klinički značaj
[uredi | uredi izvor]Varijegatna porfirija ili šarolika porfirija, uzrokovana je mutacijama u genu PPOX. U PPOX genu identificirano je više od 100 mutacija koje mogu uzrokovati ovu porfiriju. Jedna od mutacija, zamjena aminokiseline triptofana za arginin na poziciji 59 (takođe pisano kao Arg59Trp ili R59W), pronađena je u oko 95 posto južnoafričkih porodica sa šarolikom porfirijom. Mutacije u PPOX genu smanjuju aktivnost enzima kojeg proizvodi gen, omogućavajući nusproizvodima da se nagomilaju u tijelu. Ovo nakupljanje, u kombinaciji s negenetskim faktorima (kao što su određeni lijekovi, alkohol i dijeta), uzrokuje ovaj tip porfirije.
Inhibitori kao herbicidi
[uredi | uredi izvor]Inhibicija protoporfirinogen-oksidaze je mehanizam djelovanja nekoliko komercijalnih herbicida uključujući nitrofenilne etere acifluorfen, fomesafen, pirimidindione butafenacil i saflufenacil. Vidljivi simptomi liječenja su hloroza i isušivanje. Oštećenje je uzrokovano akumulacijom protoporfirina IX u biljnim ćelijama, inhibicijom protoksa unutar puta biosinteze tetrapirola.[9] Ovo je snažan fotosenzibilizator koji aktivira kisik, što dovodi do lipidne peroksidacije. I svjetlost i kisik su potrebni da bi ovaj proces ubio biljku.[10][11][12]
Također pogledajte
[uredi | uredi izvor]Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000143224 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000062729 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Taketani S, Inazawa J, Abe T, Furukawa T, Kohno H, Tokunaga R, et al. (oktobar 1995). "The human protoporphyrinogen oxidase gene (PPOX): organization and location to chromosome 1". Genomics. 29 (3): 698–703. doi:10.1006/geno.1995.9949. PMID 8575762.
- ^ Frank J, McGrath JA, Poh-Fitzpatrick MB, Hawk JL, Christiano AM (juli 1999). "Mutations in the translation initiation codon of the protoporphyrinogen oxidase gene underlie variegate porphyria". Clinical and Experimental Dermatology. 24 (4): 296–301. doi:10.1046/j.1365-2230.1999.00484.x. PMID 10457135. S2CID 40509390.
- ^ a b "Entrez Gene: PPOX protoporphyrinogen oxidase".
- ^ "UniProt, P50336" (jezik: engleski). Pristupljeno 16. 12. 2021.
- ^ Brzezowski P, Ksas B, Havaux M, Grimm B, Chazaux M, Peltier G, et al. (3. 5. 2019). "The function of PROTOPORPHYRINOGEN IX OXIDASE in chlorophyll biosynthesis requires oxidised plastoquinone in Chlamydomonas reinhardtii". Communications Biology. 2 (1): 159. doi:10.1038/s42003-019-0395-5. PMC 6499784. PMID 31069268.
- ^ Dayan FE, Reddy KN, Duke SO (1999). "Structure-Activity Relationships of Diphenyl Ethers and Other Oxygen-Bridged Protoporphyrinogen Oxidase Inhibitors". Peroxidizing Herbicides. str. 141–161. doi:10.1007/978-3-642-58633-0_5. ISBN 978-3-642-63674-5.
- ^ Nagano E (1999). "Herbicidal Efficacy of Protoporphyrinogen Oxidase Inhibitors". Peroxidizing Herbicides. str. 293–302. doi:10.1007/978-3-642-58633-0_11. ISBN 978-3-642-63674-5.
- ^ Dayan FE, Duke SO (2010). "Protoporphyrinogen Oxidase-Inhibiting Herbicides". Hayes' Handbook of Pesticide Toxicology. str. 1733–1751. doi:10.1016/B978-0-12-374367-1.00081-1. ISBN 9780123743671.
Dopunska literatura
[uredi | uredi izvor]- Elder GH (1998). "Genetic defects in the porphyrias: types and significance". Clinics in Dermatology. 16 (2): 225–33. doi:10.1016/S0738-081X(97)00202-2. PMID 9554235.
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Vansjski linkovi
[uredi | uredi izvor]- PDBe-KB provides an overview of all the structure information available in the PDB for Human Protoporphyrinogen oxidase
