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
urediDužina 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
urediTetrahidrobiopterin 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
urediMutacije 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.
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