Kushandisa Cytochrome P450 (UDP - GluculonosyltransfarissfansfarissfASFASE (DUBS yekudyidzana

Mazwi Akakosha: Dombo - Zvinodhaka Zvekudhakwa Cyp3a4 / 5, cyp2a6, cyp2e1, ugt1a3, ugt1a4, ugt1a7, ugt2b7, ugt2b15, ugt2b17, ugt2b17, ugt2b17, ugt2b17, ugt2b17, ugt2b17, ugt2b17, ugt2b17

• Maipese gadzira

Ongorora: Cyp enzymes inowanzo shandiswa neNadph Regeneration System/ NadphuyePBS
Ugt enzymes inowanzo shandiswa neUgt incubation systemuye pbs.

Metabolism inotora basa rakakosha mumugumo wemishonga, richikanganisa zvavanokwanisa mumuviri wese uye nekuita basa rekutarisa nzvimbo uye kukanganisa. Izvi zvinonyanya kuitika muchiropa, asi zvinogona kuitikawo mumatanda ezvekuwedzera. Zvidzidzo zvichangobva kuitika zvakaratidza kuvapo uye zvinoshanda kukosha kweanodhaka metabolizing enzymes (dme) muuropi.Cytochrome P450 enzyme (cyp)uyeUDP - Gluculonosyltransfase (UGT) zvakare vanokosha vechikamu mune zvinodhaka biotransformation mukati meCentral Nervous System (CNS).

• Cytochrome P450 (cyp)

Cytochrome P450 anotonga chikamu chandineti (oxidation, kuderedza, hydrolysis), accounting kweanopfuura 75% yezvinodhaka metabolism. Key Subtypes inosanganisira Cyp3a4 (50% drug metabolism) uye cyp2d6 (20% metabolism). Cyp inoshandura mishonga yemiromo yeku polar metabolites, kusimudzira nzira.

Yokutanga hepatocytes ndeye hepatown Iyo yekutanga hepatocytes modhi ndiyo yakanyanya kubvumidzwa yekuongorora muenzaniso weCyp Enzyme kuwedzeredza muindasitiri, yekudzidza, uye yekuzvidzora masangano. Semunhu cellular system, munhu eptoative

• UDP - Gluculonosyltransfase (UGT)

UDP - Gluculonosyltransfansfansfansfansfansfansferrases ⅱ Enzyme iyo inoshandisa glucoronic yeiyo clucoroni yekucheka kweiyo gluducoronic yeiyo gluducoronic yekisimusi uye mapoka ehupamhi uye kusimudzira kujekeswa kwayo. RAVE HOME rakaparadzirwa zvakanyanya uye rinoratidzwa mumatishini senge chiropa, mudumbu madiki, itsvo, dumbu, nemapapu. Chiropa ndicho chiumbwa chikuru mumuviri wemunhu icho chinoita kuti urume wecularonic asid kusunga maitiro, uye yakawanda yegt zvigoma zvinoratidzwa muchiropa. Ugt1a7, ugt1a8, ugt1a10, uye ugt2a1 inogoverwa mumatisirwo ezvekushandisa, uye gluculonic tishu

• ZVINOKOSHA ZVINOKOSHA ZVINOGONESESA

MuVitro Screening Model: Cyp kana Ugt enzymes yakadai seyechivanhu microsomes / hepatocyte incubation mishonga yeMetabolic, uye wozoongorora metabolit kugadzirwa kwemishonga yemutungamiriri (senge cyp3a4 yekuedza inhibition). Uchishandisa gene yakarongedzwa masero kufanotaura kliniki metabolic missa.

Mushonga - Kubata Kwezvinodhaka (DDI)Kudzidza: Bata Cyp Inhibition Ongororo kuti uone kuti madhiragi ekuvhiringidza Inhibit Key Cyp enzymes (senge cyp3a4) uye kufanotaura Clinical Ddi njodzi. Mufambiro Ugt Inhibition muedzo wekuongorora mhedzisiro yemishonga pane ugt chiitiko. Kuona iyo induction mhedzisiro yemishonga pane cyp / ugt kuburikidza neyepimari hepatocytes kuongororwa.

Kubudirira kweBiological Ongororo Nzira: Iyo yekudzidza yeCyp uye Ugt enzymes inotora basa rekusimudzira muBioanalytical Speetturu uye yePharmacokinetic (DMPK) zvidzidzo. Shandisa biological matrices ine cyp / ugt metabolites (senge bile uye plasma) yeiyo matrix excuation, fungai e-ms nzira, uye dzivisa ion inhibition / kusimudzira mhedzisiro.

Genetic Polymorphism Tsvaga: Ugt1a1 uye mamwe majini anodzora UPT enzyme kutaura kwakakosha majini anobatanidzwa mune zvemaguta emunhu. Nekuvandudzwa kwePharmacogenoms, yakawanikwa kuti genetic yavo polymorphism ine zvimwe zvinodhaka metabolism metabolism, iyo inokanganisa kuitika, kukura, uye kurapwa kwezvirwere uye zvimwe zvinhu zvakawanda.

Dzidza pamarudzi akasiyana siyana: Enzanisa misiyano muCyp enzyme chiitiko chePrimary Hepatows SEPTOCYME yakadai sevanhu

• Enzyme inhibition

Cyp enzyme yakadirwaenzyme inhibitionInoreva phenomenon uko mamwe makomputa anogona kundinzvera chiitiko chevamwe Cyp450 metabolic enzarism, akaderedza miti, uye kuwedzera kuratidzwa kweimwe zvinodhaka kana zvichishandiswa pakubatanidza njodzi. Zvinoenderana nemasangano akasiyana ekunzwa, iyo inhibitory yemishonga pane cyp450 enzymes inogona kukamurwa kuti ishandiswe inhibition uye nguva - inotsamira ishibition (TDI). Nguva inovimbika inhibition, inozivikanwa seisingachinjiki inhibition, kazhinji inoreva kuumbwa kweiyo yakaoma mushonga uye cyp enzyme kusungwa, zvichikonzera zvisingabvumirani enzyme kusagadzikana. Iyo inhibitory yemhedzisiro yeiyo inhibitor pane enzyme haina kungopera mushure mekunge bandbitor yabviswa, asi inoratidza nguva - hunhu hunoenderana.

• CYP450 Enzyme metabolic phenotyping kudzidza

Parizvino, pane nzira nhatu huru dzekuzivisa enzyme metazotype yeCyp450: Inosarudza Inhibition Nzira, Yekudzorerwa Human isoenyme nzira, uye nzira yekuongorora. Inosarudza Inhibition Nzira inogona kukamurwa kuita makemikari inhibition nzira uye Antibody Inhibition nzira. Izvo zvinosanganisira kuyera basa rezvemhando yemuchato wemunhu pane zvinodhaka neyekuchenjera CYP450 Enzyme metabolic phenotype. Pakati pavo, nzira yemakemikari inhibition yakave ichishandiswa zvakanyanya nekuda kwekushanda kwayo kwakareruka uye mutengo wakaderera.

• Mhedziso

Cyp enzymes uye Ugt enzymes, semucherechedzo enzyme masisitimu edhisheni Subtypes dzakadai se cyp3a4 uye cyp2d6, pamwe ne enzymes dzakadai seIgt1a1 uye ugt2b7, gadzira iyo yakaoma metabolic network. Misiyano yavo yekushandisa (yakadai seGe Possfhism uye mhando kuongororwa) inogona kuongororwa nenzira kwayo

Reference

Zhang, M., rottschään, v., & cm de lange, E. (2024). Iyo ingano inogona kukanganisa yeCyp uye ugt zvinodhaka - metabolizing enzymes pane uropi chinangwa chezviitiko kuratidzwa kwezvinodhaka. Zvinodhaka metabolism ongororo, 56(1), 1 - 30.

Ghosal, A., Ramanathan, R., Kishnani, N. S., Chowdhury, S. K., & Alton, K. B. (2005). Cytochrome P450 (CYP) uye UDP - GluculonosyltrAransfase (Ugt) enzymes: polmorphism, uye kuzivikanwa kwekubatanidzwa kwavo mune zvinodhaka metabolism. Mukati Kufambira mberi mumishonga uye biomonydical ongororo (Vol. 6, pp. 295 - 336). Zvimwe.