Ntsiab lus: Kev siv tshuaj - Yeeb tshuaj sib xyaw (DDI), Cytochrome P450 (uvxe metypoling, CYP4B6, CYP2C6, CYP2C9, CYP2C19, CYP2C19, CYP2C19, CYP2C19, CYP2C19, CYP2C19, CYP2D6, CYP3A4 / 5, CYP2A6, CYP2E1, Ugt1a6, Immt1A3, Immt1B7, Immt2b15, Immt2B17.
- IPhase tsim
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Tib neeg CYP recombant enzymes |
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Nco tseg: CYP enzymes feem ntau yog siv nrogNadph Kev Tswj Kev Ua Haujlwm/ NadphthiabPbs
Ugt enzymes feem ntau yog siv nrogUmmt Tsim Kom Tsim Txheej Txheemthiab PBS.
Cov metabolism ua si yog lub luag haujlwm tseem ceeb hauv txoj hmoo ntawm cov tshuaj, cuam tshuam rau lawv pov tseg thoob plaws lub cev thiab yog li muaj kev cuam tshuam hom phiaj thiab cuam tshuam. Qhov no feem ntau tshwm sim hauv daim siab, tab sis nws tseem yuav tshwm sim hauv cov plab hnyuv siab raum. Cov kev tshawb fawb tsis ntev los no tau qhia txog qhov muaj peev xwm thiab kev ua haujlwm tseem ceeb ntawm kev siv yeeb tshuaj metabolizing (DME) hauv lub hlwb.Cytochrome P450 enzyme (CYP)thiabUDP - GluonosylTransferase (ait) kuj tseem muaj cov neeg tuaj koom hauv cov neeg siv tshuaj yeeb hauv cov leeg ntshav hauv nruab nrab (CNS).
- Cytochrome P450 (CYP)
Cytochrome P450 Dominates theem kuv metabolism (oxidation, txo qis, nyiaj txiag rau ntau tshaj 75% ntawm cov tshuaj metabolism. Cov Ntsiab Lus Subsypes suav nrog CYP3A4 (50% yeeb tshuaj metabolism) thiab CyP2D6 (20% yeeb tshuaj metabolism). CYP Convts cov tshuaj ntxib cov tshuaj lipophilic rau hauv tsev metabolites hauv tsev polar, txhawb kev ua tiav.
Cov Hepatocytes yog Hepatocytes cais ncaj qha los ntawm tib neeg lub siab lossis tus qauv uas nyiam tshaj plaws rau kev ua haujlwm CYP enzyme thiab qhov tseeb ntawm lub cev. Thawj Hepatocytes qauv yog cov qauv kev ntsuam xyuas feem ntau lees txais CYP Enxy induction hauv kev lag luam, kev kawm, thiab cov chaw tswj xyuas. Raws li lub cellular system, tib neeg Hepatocyte yog tsim ntawm nuclear recable ntawm cov uas muaj tshuaj yeeb thiab muaj peev xwm ua tau zoo tshaj plaws ntawm cov tshuaj sib tw thiab lawv cov metabolites.
- UDP - GluonosylTransferase (ait)
UDP - Gluonossyretyrasfases yog theem tseem ceeb uas siv kib kua qaub ua kom muaj cov khoom noj kua ntses ua rau cov khoom qab zib extra thiab cov pab pawg polar, txhawb nqa cov pab pawg sib txawv. Tib neeg lub cev tsis tuaj yeem faib tawm thiab qhia tawm cov ntaub so ntswg xws li daim siab, cov hnyuv me, raum, plab, thiab lub ntsws. Lub siab yog qhov chaw ua haujlwm tseem ceeb hauv tib neeg lub cev uas tsis muaj acid los ntawm cov acid los, thiab cov UmmT subtypes yog qhia hauv daim siab. Ugt1a7, wmt1a8, wmt1a10, thiab Immta1 tau faib rau hauv cov ntaub so ntswg uas ua tau los ntawm kev nqus cov tshuaj.
- Cov ntawv thov tseem ceeb hauv kev tsim tshuaj
Nyob rau hauv vitro tshuaj ntsuam qauv: cant enzymes xws li kev ntsuas metabolic / hepatocytes siv rau kev sib tw siv cov tshuaj sib tw (xws li CYP3A4 inhibition). Siv cov noob kho kom haum rau cov neeg soj ntsuam cov teeb meem sib txawv.
Kev siv yeeb tshuaj - Kev sib xyaw (DDI)Txoj kev kawm: Kev coj Cyp Inhibition kev sim kom paub seb cov neeg siv tshuaj tsis kam lees yuav txwv tsis pub muaj kev pheej hmoo (xws li CYP3A4, CYP2C9, CYP2C9, CYP2C9 CLUT ABHIB kev sim los soj ntsuam cov nyhuv ntawm cov tshuaj ntawm akt kev ua. Tshawb nrhiav qhov ua haujlwm ntawm cov tshuaj ntawm CYP / Ummt los ntawm Thawj Hepatocytes tsom xam.
Kev tsim kho ntawm Americological Txoj Kev: Txoj kev tshawb fawb ntawm CYP thiab Ugt enzymes ua yeeb yam tseem ceeb ntawm kev siv yeeb tshuaj thiab kev siv tshuaj yeeb thiab cov tshuaj) (DMPK). Kev siv roj ntsha matrices muaj CYP / ovenn metabolites (xws li cov pa thiab ntshav) rau kev ntsuas matrix, thiab zam kom tsis txhob ion inhibition / kev cuam tshuam rau ion.
Kev tshawb fawb txog cajC Polymorphism: ugntorphism kev tshawb fawb: Kev tswj hwm uas tsis muaj dab tsi UgT enzyme hais yog cov noob metabolic sib koom tes. Nrog rau kev txhim kho cov tshuaj ntawm cov tshuaj ntawm cov tshuaj, tau pom tias lawv cov caj ces polymorphism muaj feem cuam tshuam nrog qee qib tshuaj me, kev loj hlob, thiab kev kho mob ntawm ntau yam.
Kev kawm ntawm hom sib txawv: piv cov sib txawv ntawm CYP enzyme kev ua haujlwm xws li tib neeg cov hepatocytes xws li tib neeg hepatocytes xws li cov dev sib tw los ntawm kev siv kev hloov pauv.
- Enzyme inhibition
CYP Enzyme Kho Mobenzyme inhibitionHais txog qhov tshwm sim uas qee cov chaw sib xyaw tuaj yeem cuam tshuam cov kev ua si ntawm qee cov tshuaj thaum siv kev sib xyaw ua ke, yog li cov kev phom sij nyab xeeb. Raws li cov txheej txheem sib txawv ntawm kev inhibition, inhibitos cuam tshuam ntawm cov tshuaj ntawm CYRON50 tuaj yeem faib ua kev thim rov qab thiab lub sijhawm - Nyob ze (TDI). Lub sijhawm nyob hauv, tseem muaj kev ywj pheej inhibition, feem ntau yog hais txog kev tsim ntawm tus neeg sib tw siv yeeb tshuaj thiab cypp enzyme los ntawm kev sib cav sib ceg, ua rau muaj kev sib cav sib ceg enzyme inactivation. Lub inisitosity nyhuv ntawm inhibitor ntawm enzyme tsis ploj tam sim ntawd tom qab tus inhibitor tau muab tshem tawm, tab sis cov yam ntxwv ntawm lub sijhawm - Cov yam ntxwv ntawm cov yam ntxwv.
- CYP450 enzyme metabolic kev kawm phenotyping
Tam sim no, muaj peb txoj hauv kev rau kev txheeb xyuas qhov enzyme metabolte txoj kev, kev xaiv neeg tib neeg cy450 oozyme txoj kev, thiab kev txheeb xyuas kev txheeb xyuas cov qauv. Kev Xaiv Kev Tiv Thaiv Txoj Cai tuaj yeem muab faib ua cov tshuaj inhibition thiab cov tshuaj tiv thaiv kev txwv tsis pub muaj. Nws cuam tshuam nrog kev ntsuas metabolic ntawm tib neeg lub siab ntsuas tshuaj tiv thaiv kab mob, txhawm rau txhawm rau txheeb xyuas qhov feem pua, thiab infer rau CYP450 enzyme metabolic phenotype. Ntawm lawv, cov tshuaj inhibition txoj kev tau siv dav vim nws cov haujlwm yooj yim thiab tus nqi qis.
- Tag
CYP enzymes thiab ovt enzymes, raws li cov tub ntxhais enzyme ntawm cov tshuaj metabolism, txo qis) thiab cuam tshuam nrog kev ua tau zoo, lom zem thiab siv cov tshuaj tus kheej. SUBTYPES xws li CYP3A4 thiab CYP2D6, nrog rau cov enzymes xws li Ugt1A1 thiab Immt2B7, ua ib lub network metabolic. Lawv cov kev ua si sib txawv (xws li gene polymorphism thiab hom tshwj xeeb) tuaj yeem yog cov qauv kev ua kom tau zoo los ntawm cov ntaub ntawv Hepatocytes, muab kev txhawb nqa cov ntaub ntawv tseem ceeb los ntawm kev tsim tshuaj.
Phau ntawv
Zhang, M., Rottschäfer, V., & cm de Range, E. (2024). Cov kev cuam tshuam muaj peev xwm ntawm Cyp thiab ovt cov tshuaj - metabolizing enzymes nyob rau lub hlwb cov phiaj xwm tshuaj. Kev Ntsuam Xyuas Yeeb Tshuaj Yeeb Tshuaj, 56(1), 1 - 30.
Ghosal, A., Ramanathan, R., Kishnani, N. S., C. K., Alton, K. B. (2005). Cytochrome P450 (CYP) thiab UDCuronosedrathere (agt) enzymes: polymorphism, thiab kev paub txog lawv kev koom tes hauv cov tshuaj metabolism. Hauv Kev nce qib hauv cov tshuaj thiab ntsuas kev txheeb xyuas biomedical (Vol. 6, pp. 295 - 336). Elsevier.
Lub Sijhawm Post: 2025 - 05 - 08 11:36:07