QDPR
QDPR (kvinoid dihidropteridin-reduktaza) jest ljudski gen koji je kod ljudi na hromosomu 4. Proizvodi enzim hinoid dihidropteridin-reduktaza. Ovaj enzim je dio puta koji reciklira supstancu zvanu tetrahidrobiopterin, također poznatu i kao BH4.
Aminokiselinska sekvenca uredi
Dužina polipeptidnog lanca je 244 aminokiseline, а molekulska težina 25.790 Da.[5]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MAAAAAAGEA | RRVLVYGGRG | ALGSRCVQAF | RARNWWVASV | DVVENEEASA | ||||
| SIIVKMTDSF | TEQADQVTAE | VGKLLGEEKV | DAILCVAGGW | AGGNAKSKSL | ||||
| FKNCDLMWKQ | SIWTSTISSH | LATKHLKEGG | LLTLAGAKAA | LDGTPGMIGY | ||||
| GMAKGAVHQL | CQSLAGKNSG | MPPGAAAIAV | LPVTLDTPMN | RKSMPEADFS | ||||
| SWTPLEFLVE | TFHDWITGKN | RPSSGSLIQV | VTTEGRTELT | PAYF |
Funkcija i klinički značaj uredi
Tetrahidrobiopterin djeluje enzimom zvanim fenilalanin-hidroksilaza za obradu supstance zvane fenilalanin. Fenilalanin je aminokiselina (građevni blok proteina) koja se dobija ishranom; nalazi se u svim proteinima i u nekim vještačkim zaslađivačima. Kada tetrahidrobiopterin stupi u interakciju s fenilalanin-hidroksilazom, mijenja se i mora se reciklirati u upotrebljiv oblik. Regeneracija ove supstance je kritična za pravilnu obradu nekoliko drugih aminokiselina u tijelu. Tetrahidrobiopterin također pomaže u proizvodnji određenih hemikalija u mozgu zvanih neurotransmiteri, koji prenose signale između nervnih ćelija.
Gen QDPR nalazi se na kratkom (p) kraku hromosoma 4, na poziciji 15.31, od baznog para 17,164.291 do bp 17,189.981.
U melanocitnim ćelijama, ekspresija QDPR gena može biti regulirana transkripcijskim faktorom povezanim s mikroftalmijom (MITF).[6]
Srodna stanja uredi
Mutacije u genu QDPR su čest uzrok nedostataka tetrahidrobiopterina. Identificirano je više od 30 mutacija koje uzrokuju poremećaj u ovom genu, uključujući aberantnu preradu, zamjene aminokiselina, insercije ili prijevremene terminacije. Ove mutacije potpuno ili gotovo potpuno inaktiviraju hinoidnu dihidropteridin-reduktazu, što sprečava normalno recikliranje tetrahidrobiopterina. U nedostatku upotrebljivog tetrahidrobiopterina, tijelo ne može pravilno obraditi fenilalanin. Kao posljedica toga, fenilalanin iz prehrane nakuplja se u krvotoku i drugim tkivima i može dovesti do oštećenja mozga. Neurotransmiteri u mozgu su također pogođeni, što dovodi do odgođenog razvoja, napada, poremećaja kretanja i drugih simptoma.
Osim toga, smanjenje aktivnosti hinoid dihidropteridin-reduktaze može uzrokovati abnormalno nakupljanje kalcija u određenim dijelovima mozga, što rezultira oštećenjem nervnih ćelija.
Reference uredi
- ^ a b c GRCh38: Ensembl release 89: ENSG00000151552 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015806 - 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.
- ^ "UniProt, P09417" (jezik: engleski). Pristupljeno 30. 10. 2021.
- ^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. S2CID 24698373.
Dopunska literatura uredi
- Romstad A, Kalkanoglu HS, Coskun T, Demirkol M, Tokatli A, Dursun A, Baykal T, Ozalp I, Guldberg P, Guttler F (2000). "Molecular analysis of 16 Turkish families with DHPR deficiency using denaturing gradient gel electrophoresis (DGGE)". Hum Genet. 107 (6): 546–53. doi:10.1007/s004390000407. PMID 11153907. S2CID 22889048.
- Shintaku H (2002). "Disorders of tetrahydrobiopterin metabolism and their treatment". Curr Drug Metab. 3 (2): 123–31. doi:10.2174/1389200024605145. PMID 12003346.
- Thony B, Auerbach G, Blau N (2000). "Tetrahydrobiopterin biosynthesis, regeneration and functions". Biochem J. 347 (1): 1–16. doi:10.1042/0264-6021:3470001. PMC 1220924. PMID 10727395.
- Smooker PM, Cotton RG (1995). "Molecular basis of dihydropteridine reductase deficiency". Hum. Mutat. 5 (4): 279–84. doi:10.1002/humu.1380050402. PMID 7627180. S2CID 37519191.
- Kaufman S, Holtzman NA, Milstien S, et al. (1975). "Phenylketonuria due to a deficiency of dihydropteridine reductase". N. Engl. J. Med. 293 (16): 785–90. doi:10.1056/NEJM197510162931601. PMID 1160969.
- Howells DW, Forrest SM, Dahl HH, Cotton RG (1990). "Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency". Am. J. Hum. Genet. 47 (2): 279–85. PMC 1683733. PMID 2116088.
- Sumi S, Ishikawa T, Ito Y, et al. (1990). "Probable assignment of the dihydropteridine reductase gene to 4p15.31". Tohoku J. Exp. Med. 160 (1): 93–4. doi:10.1620/tjem.160.93. PMID 2330583.
- Dahl HH, Hutchison W, McAdam W, et al. (1987). "Human dihydropteridine reductase: characterisation of a cDNA clone and its use in analysis of patients with dihydropteridine reductase deficiency". Nucleic Acids Res. 15 (5): 1921–32. doi:10.1093/nar/15.5.1921. PMC 340608. PMID 3031582.
- Lockyer J, Cook RG, Milstien S, et al. (1987). "Structure and expression of human dihydropteridine reductase". Proc. Natl. Acad. Sci. U.S.A. 84 (10): 3329–33. Bibcode:1987PNAS...84.3329L. doi:10.1073/pnas.84.10.3329. PMC 304863. PMID 3033643.
- Altmann P, Al-Salihi F, Butter K, et al. (1987). "Serum aluminum levels and erythrocyte dihydropteridine reductase activity in patients on hemodialysis". N. Engl. J. Med. 317 (2): 80–4. doi:10.1056/NEJM198707093170204. PMID 3587329.
- Brown RM, Dahl HH (1987). "Localization of the human dihydropteridine reductase gene to band p15.3 of chromosome 4 by in situ hybridization". Genomics. 1 (1): 67–70. doi:10.1016/0888-7543(87)90106-6. PMID 3666748.
- Nakanishi N, Hasegawa H, Yamada S, Akino M (1986). "Purification and physicochemical properties of NADPH-specific dihydropteridine reductase from bovine and human livers". J. Biochem. 99 (3): 635–44. doi:10.1093/oxfordjournals.jbchem.a135522. PMID 3711039.
- Armarego WL, Ohnishi A, Taguchi H (1986). "New pteridine substrates for dihydropteridine reductase and horseradish peroxidase". Biochem. J. 234 (2): 335–42. doi:10.1042/bj2340335. PMC 1146570. PMID 3718470.
- Shen RS, Smith RV, Davis PJ, Abell CW (1984). "Inhibition of dihydropteridine reductase from human liver and rat striatal synaptosomes by apomorphine and its analogs". J. Biol. Chem. 259 (14): 8994–9000. doi:10.1016/S0021-9258(17)47254-1. PMID 6746636.
- Firgaira FA, Choo KH, Cotton RG, Danks DM (1982). "Molecular and immunological comparison of human dihydropteridine reductase in liver, cultured fibroblasts and continuous lymphoid cells". Biochem. J. 197 (1): 45–53. doi:10.1042/bj1970045. PMC 1163053. PMID 6797415.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Katoh S, Sueoka T, Yamamoto Y, Takahashi SY (1994). "Phosphorylation by Ca2+/calmodulin-dependent protein kinase II and protein kinase C of sepiapterin reductase, the terminal enzyme in the biosynthetic pathway of tetrahydrobiopterin". FEBS Lett. 341 (2–3): 227–32. doi:10.1016/0014-5793(94)80462-1. PMID 8137944. S2CID 35666601.
- Su Y, Varughese KI, Xuong NH, et al. (1994). "The crystallographic structure of a human dihydropteridine reductase NADH binary complex expressed in Escherichia coli by a cDNA constructed from its rat homologue". J. Biol. Chem. 268 (36): 26836–41. doi:10.2210/pdb1hdr/pdb. PMID 8262916.
- Dianzani I, Howells DW, Ponzone A, et al. (1993). "Two new mutations in the dihydropteridine reductase gene in patients with tetrahydrobiopterin deficiency". J. Med. Genet. 30 (6): 465–9. doi:10.1136/jmg.30.6.465. PMC 1016417. PMID 8326489.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Lin CM, Tan Y, Lee YM, et al. (1998). "Expression of human phenylalanine hydroxylase activity in T lymphocytes of classical phenylketonuria children by retroviral-mediated gene transfer". J. Inherit. Metab. Dis. 20 (6): 742–54. doi:10.1023/A:1005303331218. PMID 9427141. S2CID 22653168.
- Dianzani I, de Sanctis L, Smooker PM, et al. (1998). "Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations". Hum. Mutat. 12 (4): 267–73. doi:10.1002/(SICI)1098-1004(1998)12:4<267::AID-HUMU8>3.0.CO;2-C. PMID 9744478.