Sulfotransfesferase (Sult) oo loogu talagalay cilmi-baarista DDI, xasilloonida dheef-shiid kiimikaadka, iyo xakamaynta enzyMyme

Erayada muhiimka ah enzyme

1 iPhose wuxuu soosaaraa

2 daraasad cilmi baaris ah oo ku saabsan horumarka daroogada

Marka laga hadlayo daroogada, daraasadda daroogada dheef-shiid kiimikaad iyo caqabadaha enzyMyme ee dheef-shiid kiimikaad sida Cyp450, UGT, Sult, iwm. Cilmi-baarista cirbadaha dheef-shiid kiimikaad ee loo yaqaan 'phonotype phenotype' ee loo yaqaan 'phonotype prenotype' oo lagu daro LC - Ms. Ms / tikniyoolajiyada dheef-shiid kiimikaadka, iyo remaxs-ka kharakadda (sida pmax) ee daroogada, oo ay qiimeeyaan saameynta polmy polmyrorphism-ka. Cilmi-baarista xannibaynta ee enzyMyme wuxuu diiradda saaraa saameynta daroogada xannibaya ee daroogada ama xeryahooda ku saabsan cunnada dheef-shiid kiimikaadka (sida is-xakamaynta / wax lagu cabbiro ee la beddeli karo), cabbiraya qiyamka IC50 / KI ee saadaalintaDawooyinka - Is dhexgalka daroogada (DDI)halis. Daraasadahaani waxay bixiyaan saldhigyo cilmiyeed oo loogu talagalay in lagu muujiyo naqshada daroogada, qiimeynta amniga (sida aqoonsashada dadka loo yaqaan 'sumadda sunta', iyo hagaynta dawada saxda ah. Caqaarka asaasiga ah wuxuu ku yaal badalka ku-beddelka vitro ee xogta vivo iyo ogaanshaha ogaanshaha dadka dheecaanka badan ee dheecaanka badan. Mustaqbalka, moodooyinka horumarsan sida unugyada unugyada waxaa loo isticmaali karaa in lagu wanaajiyo isku hallaynta cilmi baarista.

3 sulfotriansferase (Sult)

SulfotriansFrese (Sult)waa nooc ka mid ah wareejinta oo ka kooban wareejinta kooxaha Sulfate waxayna ku lug leedahay dheef-shiid kiimikaad ee xermoonka andogenous (sida hormoonnada iyo neurotransmitters) iyo xeryaha chorogenous (sida wasakhaha deegaanka). SulfotransFres -s-ka badanaa waxay ku yaalliin qalabka cytoplasm iyo goluga, oo ku lug leh sulgacation of sulgaca-ka yar yar ee molecuule (sida dawooyinka, kuwa neurotransmitters) iyo molosules, sida plotes-ka, borotiinnada, glycosamatamoglycans). SulfotransFresFersFersFersFersFersFersFersFersFeases ayaa loo aqoonsaday inay yeeshaan noocyo badan, oo badanaa ay ku jiraan Sult1, Sult2, iyo Sult4. Qulqulka sulfotransfuska waxay u horseedi kartaa dheef-shiid kiimikaad aan caadi ahayn, kansarka, cilladaha endocrine, iyo ciladaha neerfaha.

4 Dheef-ka Sulbasho-ka

Dheef-shiid kiimikaad Sulfonal (oo sidoo kale loo yaqaan 'Sulfonation' (oo sidoo kale loo yaqaan 'Sulbolem-ka' Sulbolism Dheef-shiid kiimikaad) wuxuu door muhiim ah ka ciyaaraa tuurista Vivo ee daroogada wuxuuna aasaas muhiim u yahay horumarinta daroogada cusub iyo isticmaalka daroogada caafimaadka ee cusub. Sulmatase-ka salfotransferase (oo sidoo kale loo yaqaan sulfatase) waxay leedahay tiro balaaran oo jidhka ka mid ah, badiyaa waxaa loo qaybiyaa xubnaha jirka, xiidmaha yaryar, kelyaha, iyo sambabbada. Caanooyinka guud ee bini'aadamka waxaa ka mid ahSult1A1, Sult1A3, Sult1b1, Sult1c2, iyoSult1c4 (Shaxda 1). Inta badan substrates, sulfotransferesferase dheef-shiid kiimikaad ee dhexdhexaadinta ah ayaa inta badan soo bandhigaya astaamaha xakamaynta is-hoosaadka ee caadiga ah; Heerarka uruurinta hoose ee sunta hoose ayaa caadi ahaan ku dhajiya muuqaalka enzyme.

Shaxda 1 qaybinta iyo shaqada qayb ahaan Sult Superfamily ee jirka bini aadamka

5 Codsiyada Muhiimka ah ee Sult ee Horumarinta Daroogada

5.1 Qiimaynta cudurka vitrotro ee DDI ee ku saleysan dheef-shiid kiimikaadka

Qiimaynta ku saabsan Sult ee dhexdhexaadka ah ee loo yaqaan 'vetro' ee dhexdhexaadinta lagu daweeyo DDI waxaa lagu sameeyaa ka hortagga xulashada (sida Querertkin, DCNP) ama nidaamyada enzyme ee dib-u-soo-kabashada ee loo yaqaan 'clutoplas' ee loo yaqaan 'clutops' ee loo yaqaan 'squatic'. Naqshadeynta tijaabadadu caadi ahaan waxaa ka mid ah:

Falanqaynta Photolic-ka-dib-u-eegista: Quantify the rate of sulfated metabolite generation by LC-MS/MS and calculate the inhibition rate (IC50/Ki value).

Saadaalinta khatarta caafimaad: Haddii xantubo uu si weyn u yareeyo waxsoosaarka metabolite (heerka xakamaynta> 50%), waxay faragalin ku sameyneysaa nadiifinta dafaynta, oo dheeraad ahna waxaa loo baahan yahay ansaxinta vivo.

5.2 Daraasadda Xasaasidda Dhiig ee Sult

Horumarinta daroogada, daraasadda xasilloonida dheef-shiid kiimikaadka ee Sult-ka waxaa lagu sameeyaa vitro-cytoplasm / APS) oo ay weheliso tabarucyo Sult - MS / MST CYPESST, iyo Qalliinka Tirada Dheeraadka ah, iyo Khatarta Kordhinta dheef-galeenka dheef-galeenka, iyo hagaynta kobcinta qaabdhismeedka.

5.3 Cilmi baarista Subbalic-ka

Habka cilmi baarista ee substrate (Qaabka Aqoonsiga dheef-galeenka dheef-galeenka) ee Sult wuxuu si toos ah u tixraacayaa qaabeynta enzymes Cyp, kaas oo uu marka hore u adeegsado xakameynno noocyo ah oo la xiriira shaashadda, ka dibna u xisaabaya abaalmarinta hidde-ku-dejinta oo xisaabisa tabarucaadda wadaha.

Mabda 'weyn iyo wado farsamo oo ah Imtixaanka xakamaynta kiimikada ee Sult waa in la qiimeeyo in dheef-soosaarka hooyada ama soosaarka metabolite ay ka horjoogsanayso xargaha xulashada Xulka Queener ah iyo DCNP ee Nidaamka Cypatic Cymoplasm.

5.4 Enzyme Cilmi baarista

Sult waxay ku lug leedahay dheef-shiid kiimikaad walxaha badan ee daroogada iyo daroogada. Haddii daroogooyinka loo horumariyo si loo xakameeyo waxqabadka Sult, waxaa jiri kara arrimo badbaadada suuragalka ah marka la wadaago daroogada. Mabda 'weyn iyo dariiqa farsamada ee Sult Enzyme-ka Assay waa in la ogaado Nidaamka Enzyme Piay Piay-ka si loo ogaado in wax soo saarka metabolite p' NitropholeNol Sallate P - nitrophenol-ka sida P - nitrophenol.

6 Gunaanad

Sulfotriansferase (Sult) wuxuu door muhiim ah ka ciyaaraa dheef-shiid kiimikaadka daroogada, daroogada - Is dhexgalka daroogada (DDI), iyo qiimeynta amniga. Dheef-shiid kiimikaadka muabshadda ah ee ay dhexdhexaadinayso waxay saameyn ku yeelataa nadiifinta daroogada, firfircoonida, ama sunta (sida dheef-shiid kiimikaadka dawooyinka hoormoonka iyo wasakhda deegaanka), halka daraasadeyaasha deegaanka), halka daraasadihii isqaba ee enzyme-ka ay saadaali karaan khatarta kiliinikada. Iyaga oo isku daraya moodooyinka cudurka vetroplasm (cytoplasm-ka beerka, dib-u-dejinta) ee LC / tikniyoolajiyada dheef-shiid kiimikaadka ee nafaqada Squloy (Suldha) waa la caddeyn karaa, in la caddeeyo qaab dhismeedka daroogada iyo dawooyinka. Mustaqbalka, moodooyinka horumarsan sida unugyada loo yaqaan 'blorgadoids' waxay sii xoojin doontaa qiimaha tarjumaadda ee cilmi baarista Sult, iyadoo la siinayo shuruudo sax ah oo qiimeyn ah oo ku saabsan xasilloonida dheef-shisheeyaha iyo nabdoonaanta horumarka daroogada.

Qoraal ka warbixineya

Li, Y., Lindsay, J., Wang, L. L. L. L. L., S. S. S. (2008). Qaab-dhismeedka, shaqada iyo polymor promyphismka ee sultotrins-ka kufsada bini-aadamka. Dheef-ka-dheelitirka daroogada ee hadda jira, 9(2), 99 - 105.