Codsiga cytochrome p450 (Cym450) iyo UDP - GlucauronosyltranyltranyfsFransFransFrase (UDT) Enzymes-ka EnzyMes ee Dawooyinka is dhexgalka Dawooyinka

Erayada muhiimka ah: Dawada Cyp3A4 / 5, Cyp2E6, Cyp2E1, Ugt1A1, Ugt1A4, Umb1A7, Ugt1A7, Ugt1A1, Ugt1A1, Ugt1B15, Ugt1B7, UGT1B15, UGT10.

• IPhope wax soo saarka

Xusuusin: Enzymes Cym-ka waxaa badanaa loo isticmaalaaNidaamka dib-u-cusboonaysiinta Nalaph/ NaadphiyoPBS
Ent enzymes waxaa badanaa loo isticmaalaaNidaamka UGTiyo PBS.

Dheef-shiid kiimikaadku wuxuu door muhiim ah ka ciyaaraa masiirka daroogada, taasoo saameyn ku yeelanaysa qashin-qubka jirka oo dhan, sidaas darteedna saameyn ku yeelata soo-gaadhista goobta iyo saameynta. Tani waxay badanaa ku dhacdaa beerka, laakiin waxay sidoo kale ku dhici kartaa xubnaha ka baxsan. Daraasadihii ugu dambeeyay ayaa shaaca ka qaaday jiritaanka iyo muhiimadda ay sii shaqeeyaan ee dawada dheecaanka daroogada enzymes (DME) maskaxda.Cytochrome p450 enzyme (Cyp)iyoUDP - Glucauronosyltranyltrase (UGT) Sidoo kale waa kaqeybgalayaasha muhiimka ah ee daroogada biotraska ee ka dhex jira nidaamka neerfaha dhexe (CNS).

• Cytochrome P450 (CYP)

Cytochrome P450 waxay ku guuleysatay wajiga dheef-shiid kiimikaadka (oksilation, dhimista, hydrolysis), oo lagu xisaabiyo in ka badan 75% dheef-shiid kiimikaad daroogada. Cutubka muhiimka ah waxaa ka mid ah Cyp3A4 (50% dheef-shiid kiimikaad) iyo Cyp2D6 (20% dheef-shiid kiimikaad daroogada). Cypgu wuxuu ku beddelaa daroogada lipophophilic-ka galay medutal-ka baastada, kor u qaadista excretion.

Heepocytes-ka aasaasiga ah ayaa si toos ah looga go'doomay beerka aadanaha ama xoolaha, waxayna noqdeen moodalka doorbida dawada dheef-ka-ciladaha dawada ee loo yaqaan 'Dheef-ka-daroogada daroogada ay sabab u tahay ilaalintooda waxqabadka CYP ee Cilmiga CYP ee Cilmiga Cilmiga CYP ee Cilmiga Cilmiga CYP. Qaabka aasaasiga ah ee hepatocytes-ka ayaa ah nooca qiimeynta si weyn loo aqbalo ee loogu talagalay in lagu muujiyo CYPZMME ee warshadaha, tacliinta, iyo hay'adaha sharci-darrada. Sida nidaamka unugyada, hepatocyte aadanaha ayaa ka kooban soo-dhahayaasha nukliyeerka ah, u guuristayaasha, bartilmaameedyada hidda-wadaha iyo dhiirrigelinta dawada, iyo kuwa wax ku oolka ah ee si wax ku ool ah u dhigan kara daroogada musharraxiinta iyo metabolites.

• UDP - Glucauronosyltranyltrase (UGT)

UDP - Glucauronosyltresfers -s waa waji aasaasi ah ⅱ enzyme oo adeegsanaya aashitada glucauronic sida tabaruc sonkor ah oo ay u dhigto xididdada glucuuronic acid glucauronic iyo kooxaha wabiga, kor u qaadista cadeyntooda. Ugt dadka aadanaha ayaa si ballaaran loogu qaybiyaa loona muujiyaa unugyada sida beerka, xiidmaha yaryar, kilyaha, caloosha, iyo sambabbada. Beerku waa xubinta ugu weyn ee jirka bini-aadamka ee maraya jawaab celinta aashitada glucauronic acid ee glucauronic, iyo cufnaanta ugu badan ee ugxantu waxaa lagu muujiyaa beerka. UGT1A7, UGT1A8, UGT1A10, iyo UGT2A ayaa lagu qaybiyaa unugyo lama-dhaafsan, iyo falcelinta xididdada glucauronic ee ka dhacaya unugyada isdaba-kaca ah inta badan waxay la xiriiraan nuugista iyo ka saarista daroogada.

• Codsiyada muhiimka ah ee horumarka daroogada

Moodeelka Baadhitaanka ee Vitro: Cyp ama enzymes cymt sida mikrococytes beerka / hepatocytes-ka aasaasiga ah ee loo yaqaan 'Mirpatocytes-ka' / hepatocytes-ka) ee lagu qiimeeyo dheef-galeenka iyo nus-saac ee mukhaadaraadka dheef-galeenka, sida CYPOL-da-munications-ka (sida Cyp3A4a4 tijaabinta Cyp3A4. Adeegsiga unugyada hidda-wadaha si loo saadaaliyo khilaafaadka dheef-galeenka dheecaanka.

Daroogada - is dhexgalka daroogada (DDI)Daraasad: Samee tijaabooyin xasaasi ah oo Cym ah si loo ogaado in musharraxa musharraxiinta ah ee daroogada musharraxiinta ahi ay xakameeyaan furaha Cymy-ka (sida Cyp3A4, Cyp2C9) oo saadaaliso halista xarunta caafimaadka ee Cyp2C. Samee tijaabooyin xannibaadda ka hortaga UGT si aad u qiimeyso saameynta daroogada ee waxqabadka UGT. Ogaashada saameynta laqabsashada daroogada ee Cyp / UGT iyada oo loo marayo falanqaynta aasaasiga ah ee hepatocytes-ka.

Horumarinta qaababka falanqaynta bayoolojiga ah U adeegso matricyada bayoolajiga ah

Baadhitaanka hidde-wadaha 'PLETY PLYMRISM' Kobcinta biibiyeyaasha Pilliogens, waxaa la ogaaday in hidde-side-wadaha oo kale ay la xiriirto heerarka dheef-galeenka daroogada qaarkood, oo isugeyn ah ay saameyso dhacdada, horumarka, iyo dawooyinka cudurada iyo dhinacyo kale oo badan.

Daraasad ku saabsan kala duwanaanshaha noocyada: isbarbar dhig farqiga u dhexeeya Waxqabadka Cyp Enzyme ee hepatocymes-ka aasaasiga ah sida aadanaha, jiirka, iyo eeyaha, iyo hagaajinta istiraatiijiyadda kala-guurka ee loo adeegsado isticmaalka caafimaad.

• Is-xakameynta enzymanme

Cymyme enzyme dhexdhexaadintais-xakameynta enzymanmeWaxaa loola jeedaa ifafaaleyaasha ay xarumaha qaarkood xakameyn karaan waxqabadka eyz45-ka dheef-shiid kiimikaad ee Cyp450, oo ay ku kordheen qiimayaasha yareeya, iyo soo-gaadhista daroogada qaarkood marka loo isticmaalo isku-darka, taas oo ay jirto halis nabadgelyo. Marka loo eego qaababka kala duwan ee xannibaadda, saamaynta xannibaynta daroogada ee dawooyinka Cyp450 enzymes-ka waxaa loo qaybin karaa xannibaadda dib-u-eegida iyo waqtiga - Xaraashka (TDI). Waqtiga ku-hortagida waqtiga, oo sidoo kale loo yaqaan xakamaynta wax lagu xakameeyo, guud ahaan waxaa loola jeedaa samaynta isku dhafan ee daroogada musharraxiinta iyo cyp enzyme iyada oo loo marayo dammaanad-celinta codka, taasoo dhalisay enzyme enzyme enzyme-ka aan la fahmi karin. Saamaynta xannibaynta ee xakamaynta enzyme-ka si dhakhso ah uma baabiiso ka dib markii la joojiyo, laakiin uu waqti soo bandhigayo - astaamaha ku tiirsanaanta.

• Cym450 enzyme enzyme phenolic-ka '

Waqtigan xaadirka ah, waxaa jira seddex habab oo waaweyn oo loogu talagalay in lagu garto sawirka 'dheeflic-ka' enzyme-shiid kiimikaad ee Cyp450: Qaabka loo yaqaan 'Xawaare' Cym45-ka ', dib-u-soo-celinta Qaabka loo yaqaan' aprem45-ka 'Cym450 Ilonzyme', iyo habka falanqaynta xiriirka. Habka xakamaynta xulashada ah ayaa loo qaybin karaa hab kiimiko dhiig xakameyn ah iyo habka xakamaynta antibody. Waxay ku lug leedahay cabbiridda waxqabadka dheef-shiid kiimikaadka microcolics beerka aadanaha ee daroogada oo aan ka hortagin cudurada kiimikada ee Cyp450 enzyme, xisaabiyaan boqolkiiba beerka ee qaraabada, oo ay ka tagtay Cyp450 phenolic-ka dheef-shiid kiimikaad ee enzyMyme. Waxaa ka mid ah, habka kiimikada kiimikada si weyn loo istcimaalo hawlgalkeeda fudud iyo qiimaha jaban.

• Gabagabo

CYP Enzymes iyo enzymes entMymes, oo ah nidaamyada enzyme ee dheef-shiid kiimikaadka dawada, oo si xushmad leh u kala horeeya, oo hoos u dhac ah, oo hoos u dhac ah) iyo wajiga II (si qoto dheer u saameynaya waxtarka, sunta, iyo isticmaalka shaqsiyeedka. Cutub sida Cyp3A4 iyo Cyp2D6, oo ay weheliso enzymes sida Umb1A1 iyo UGT2B7, waxay sameeyaan shabakad dheef-shiid kiimikaad oo adag. Firfircoonaanta firfircoonida (sida hiddo-wadeyaasha hiddo-wadaha iyo noocyada gaarka ah) ayaa si sax ah loo falanqeeyaa moodooyinka aasaasiga ah ee hepatocytes iyo LC -

Qoraal ka warbixineya

Zhang, M., Rottschäfer, V., & cm de Leasge, E. (2024). Saamaynta suurta galka ah ee daroogada Cyp iyo daroogada UGT - Metabolize Enzymes oo ku saabsan soo-gaadhista maandooriyaha maskaxda. Dib-u-eegista Daroogada, 56(1), 1 - 30.

Ghosol, A. Ramasathan, R., Kishnani, N. S., Chowdhy, S. K., iyo Alton, K. B. (K. B. (K. B. Cytochrome P450 (CYP) iyo UDP - Glucauronosyltranyltransferase (UDT) Enzymes: Doorka dheef-galeenka daroogada, polymorphalism, iyo aqoonsashada ku lug lahaanshahooda dawada dheef-shiid kiimikaadka daroogada. Gudaha Horumarka farmasiiga dawooyinka iyo falanqaynta biomedical (Vol. 6, pp. 295 - 336). Elsevier.