Sulfotransferase (SULT) maka nyocha DDI, nkwụsi ike nke metabolic, na mgbochi enzyme.

Isi okwu: ọgwụ - mmekọrịta ọgwụ ọjọọ (DDI), sulfotransferase (SULT), mgbochi enzyme, SULT metabolic, metabolic kwụsie ike, mmadụ SULT1A1 enzyme, mmadụ SULT1A3 enzyme, mmadụ SULT1B1 enzyme, mmadụ SULT1C2, mmadụ SULT1C4 enzyme, mmadụ SULT1E1 enzyme, mmadụ SULT2A1 enzyme.

1 IPHASE na-emepụta

2 Nnyocha Enzymatic na mmepe ọgwụ

Na mmepe ọgwụ, ọmụmụ nke phenotypes metabolic na mgbochi enzyme nke enzymes metabolic dị ka CYP450, UGT, SULT, wdg dị oke mkpa. Metabolic phenotype nnyocha na-eji in vitro ụdị jikọtara ya na LC-MS/MS teknụzụ iji chọpụta ndị bụ isi metabolic ụzọ, isi metabolic enzymes, na ha kinetic parameters (dị ka km/Vmax) nke ọgwụ, na-atụle mmetụta nke gene polymorphism na ọgwụ ahaziri. Nnyocha mgbochi nke Enzyme na-elekwasị anya na mmetụta mgbochi nke ọgwụ ma ọ bụ ogige na enzymes nke metabolic (dị ka mgbochi na-agbanwe agbanwe / nke a na-apụghị ịgbagha agbagha), na-atụle ụkpụrụ IC50/Ki iji buru amụma.ọgwụ - mmekọrịta ọgwụ (DDI)ihe ize ndụ. Ọmụmụ ihe ndị a na-enye ntọala sayensị maka ịkwalite imepụta ọgwụ, nyocha nchekwa (dị ka ịchọpụta metabolites na-egbu egbu), yana iduzi ọgwụ ziri ezi. Isi ihe ịma aka bụ ntụgharị nke in vitro ka ọ bụrụ data in vivo yana nhụta mmetụta nke metabolites dị ala. N'ọdịnihu, enwere ike iji ụdị dị elu dị ka organoids mee ka ntụkwasị obi nyocha dịkwuo elu.

3 Sulfotransferase (SULT)

Sulfotransferase (SULT)bụ ụdị transferase nke na-eme ka nnyefe nke otu sulfate dị iche iche na-etinye aka na metabolism nke ogige endogenous (dị ka hormones na neurotransmitters) na ogige exogenous (dị ka ọgwụ ọjọọ na gburugburu ebe obibi). Sulfotransferases dị na cytoplasm na ngwa Golgi, na-etinye aka na sulfation nke obere mkpụrụ ndụ (dịka ọgwụ, homonụ, neurotransmitters) na nnukwu ụmụ irighiri ihe (dị ka peptides, protein, lipids, glycosaminoglycans). Achọpụtala Sulfotransferases nwere ọtụtụ ụdị subtypes, ọkachasị gụnyere SULT1, SULT2, na SULT4. Arụghị ọrụ nke sulfotransferase nwere ike bute ọrịa metabolism na-adịghị mma, ọrịa kansa, ọrịa endocrine, na ọrịa akwara ozi.

4 Sulfation/Sulfation Metabolism

Sulfonation metabolism (nke a makwaara dị ka sulfation metabolism) na-arụ ọrụ dị mkpa na mkpofu ọgwụ na vivo ma bụrụ ntọala dị mkpa maka mmepe ọgwụ ọhụrụ yana iji ọgwụ eme ihe. Sulfotransferase mmadụ (nke a makwaara dị ka sulfatase) nwere ụdị ihe dị iche iche n'ime ahụ, na-ekesa na akụkụ ndị dị ka imeju, obere eriri afọ, akụrụ, na ngụgụ. SULT nke mmadụ nkịtị gụnyereSULT1A1, SULT1A3, SULT1B1, SULT1C2, naSULT1C4 (tebụl nke 1). Maka ọtụtụ mkpụrụ, sulfotransferase mediated metabolism na-egosipụtakarị njirimara mgbochi nke mkpụrụ osisi; Ọnụnọ nke mkpụrụ osisi dị ala na-ebute okwu enzyme.

Isiokwu 1 Nkesa na ọrụ nke obere ezinụlọ SULT n'ime ahụ mmadụ

Ngwa 5 bụ isi nke SULT na mmepe ọgwụ

5.1 In Vitro Evaluation of DDI Dabere na Metabolism

A na-eme nyocha in vitro nke SULT mediated DDI site na ndị inhibitors (dị ka quercetin, DCNP) ma ọ bụ sistemu enzyme recombinant na cytoplasm hepatic mmadụ ma ọ bụ ụdị cell na-egosipụta ụdị SULT akọwapụtara. Nhazi nnwale na-agụnyekarị:

Metabolic phenotype analysis: Gbakọọ ọnụego ọgbọ metabolite sulfated site na LC-MS/MS wee gbakọọ ọnụego mgbochi (ọnụahịa IC50/Ki).

Amụma ihe ize ndụ nke ụlọ ọgwụ: Ọ bụrụ na onye na-egbochi ya na-ebelata mmepụta metabolite (ọnụego mgbochi> 50%), ọ na-atụ aro na ọ nwere ike igbochi mkpochapụ ọgwụ ndị dabere na metabolism SULT, yana n'ihu na vivo nkwado dị mkpa.

5.2 SULT Ọmụmụ nkwụsi ike nke metabolic

Na mmepe ọgwụ, ọmụmụ nke SULT metabolic kwụsie ike na-eduzi site na in vitro incubation (hepatic cytoplasm/APS) jikọtara ya na LC-MS/MS analysis iji chọpụta ọgwụ sulfation ọnụego na metabolite ọgbọ, chọpụta isi SULT subtype onyinye, na-enyocha ihe ize ndụ nke metabolic, na-eduzi nhazi njikarịcha.

5.3 Nchọpụta nke mkpụrụ ndụ metabolic

Usoro nyocha mkpụrụ (usoro njirimara metabolic) nke SULT nwere ike na-ezo aka ozugbo na imepụta enzymes CYP, nke mbụ na-eji mgbochi kemịkalụ nyocha maka ụdị subtypes dị mkpa, wee nyochaa ha site na recombinases mkpụrụ ndụ ma gbakọọ ntinye aka ha.

Isi ụkpụrụ na ụzọ teknụzụ nke nnwale mgbochi kemịkalụ nke SULT bụ inyocha ma egbochiri metabolism nke nne ma ọ bụ mmepụta metabolite site n'ịgbanwe ndị na-emechi emechi Quercetin na DCNP nke SULT na sistemu cytoplasm nke imeju mmadụ.

5.4 Nnyocha Mgbochi Enzyme

SULT na-etinye aka na metabolism nke ọtụtụ ihe endogenous na ọgwụ. Ọ bụrụ na a na-emepụta ọgwụ iji gbochie ọrụ SULT, enwere ike ịnwe nsogbu nchekwa mgbe ị na-ekekọrịta ọgwụ. Isi ụkpụrụ na ụzọ ọrụ aka nke SULT enzyme inhibition assay bụ iji SULT dị ọcha enzyme usoro iji chọpụta ma mmepụta nke metabolite p-nitrophenol sulfate na-egbochi site n'ịgbakwunye ọgwụ nyocha na ihe nyocha dịka p-nitrophenol.

6 Nkwubi okwu

Sulfotransferase (SULT) na-arụ ọrụ dị oke egwu na metabolism ọgwụ, ọgwụ - mmekọrịta ọgwụ (DDI), na nyocha nchekwa. Metabolism sulfation nke na-agbazinye ya na-emetụta mkpochapụ ọgwụ, ịgbalite, ma ọ bụ nsi (dị ka metabolism nke ọgwụ homonụ na mmetọ gburugburu ebe obibi), ebe ọmụmụ mgbochi enzyme nwere ike ibu amụma ihe egwu DDI ụlọ ọgwụ. Site na ijikọ ụdị vitro (cytoplasm imeju, enzymes recombinant) na teknụzụ LC - MS/MS, enwere ike ịkọwapụta onyinye metabolic nke subtypes SULT (dịka SULT1A1, SULT2A1), na-eduzi njikarịcha usoro ọgwụ na ọgwụ ahaziri iche. N'ọdịnihu, ụdị dị elu dị ka organoids ga-eme ka uru ntụgharị nke SULT dịkwuo mma, na-enye usoro nyocha nke ọma maka nkwụsi ike nke metabolic na nchekwa na mmepe ọgwụ.

Ntụaka

Li, Y., Lindsay, J., Wang, L. L., & Zhou, S. F. (2008). Ọdịdị, ọrụ na polymorphism nke mmadụ cytosolic sulfotransferases. Metabolism ọgwụ ugbu a, 9(2), 99-105 .