Ngwa nke Cytochrome P450 (CPL450) na UDP - Ọmụmụ Ihe Ọgwụ

Okwu isiokwu: Ọgwụ - Usoro Omume (DDI), Cytochrome P450 (CPLYE), CPLYENTENTYLTETICS (CPLYA), CPL2C8, CPP2C1, CPP2C1, CPP2C6, CPP3 / 5, CPP2A6, CPP2A1, UGT1A1, UGT1A, Ugbo1, Ugt1A, Ugt1A, Ugt1A, Ugt2B7, Ugt2b7, Ugt2b7, Ugt2b7, Ugt2b7, ugt2b15, ugt2b15, ugt2b15, ugt2b15, ugt2b15, ugt2b15, ugt2b15, ugt2b15, ugt2b15, ugt2b)

• IFPAS

Mara: A na-ejikarị CPMyUsoro nchịkọta nke Nadph/ NidphnaPbs
A na-ejikarị UGTSistemụ Ugt Incubetionna pbs.

Metabolism na-arụ ọrụ dị oke mkpa na akara ube, na-emetụta ahụ n'ime ahụ ha niile wee si otú ahụ na-emetụta oke mgbasa ozi na mmetụta. Nke a tumadi na imeju, mana o nwekwara ike ime na akuku uzo uzo. Ọmụmụ ihe ndị na-adịbeghị anya ekpughere ịdị adị na nke ọgwụ ọgwụ ike (DME) na ụbụrụ.Cytochrome P450 enzyme (CP)naUdp - glucuurosltraseral (ugt) bụ ndị sonyere na-eme ihe na-egbu egbu n'ime ọgwụ nje dị n'etiti sistemụ ụjọ (CNS).

• Cytochrome P450 (CP)

Cytochrome P450 na-achịkwa oge m metabolism (oxidation, mbelata, na-egosiputa ihe karịrị 75% nke metabolism ọgwụ ọjọọ. Igodo Igodo gụnyere CPP3A4 (50% ọgwụ ọjọọ) na Cyp2d6 (20% metabolism ọgwụ). Cyp tụgharịrị ọgwụ ọjọọ n'ime arịa polar, na-akwalite excretion.

Isinkatocytes bụ hpatocytes kewapụrụ ya site na imeju mmadụ ma ọ bụ anụmanụ, ọ bụrụgodị ihe a na-ahọrọ maka nyocha nke ọgwụ Cyp enzyme na-arụ ọrụ. Ihe nlereanya Hepatocytes bụ ihe a na-anakwere ihe nlereanya nyocha nke CPy enzyme Ntinye ụlọ ọrụ, agụmakwụkwọ, na ụlọ ọrụ nchịkwa. Dị ka usoro cellular, ndị na-anabata mmadụ na-anabata mmadụ nuklia, ụdị mkpụrụ ndụ ihe nketa, yana ọgwụ imeju na-eme ka ịnyalite ọgwụ nke ịdeụ ọgwụ na ndị metaboli ha.

• Udp - glucuurosltraseral (ugt)

UDP - glucuurosyltrasfes bụ ihe mmalite ⅱ enzyme na-eji akwa shuga na-eji ihe ndị na-enye ya acid na-eme ka ọ bụrụ ihe na-egbu egbu na polale, na-akwalite nghapụ ya. A na-ekesa Ugt mmadụ ma gosipụta na anụ ahụ dịka imeju, obere eriri afọ, akụrụ, afọ na ngụgụ. Imeju na-emeju na aru mmadu nke na - eme mmeghachi omume nke glugwaur na - eme ka mmeghachi omume nke glugwaur. UGT1A, UGT1A, UGT1A1A, na Ugt2AACE na-eme ihe mmeghachi omume nke gluruake na-eme na akwara na-eme ihe bụ ihe metụtara ọgwụ.

• Ngwa dị na mmepe ọgwụ

Na Vitro ma ọ bụ Ugt enzymes dị ka micromes / isi ọgwụ mgbochi na ọkara mineral incured nke ọgwụ ọgwụ (dịka CPP3A4 na-egbochi onwe ya). Na-eji Gene deziri mkpụrụ ndụ ka ọ ga-ebu amụma metabolical metabolic.

Ọgwụ - Usoro Omume (DDI)Ọmụmụ: na-eduzi nyocha CyBinking nchọpụta ma nwa agbọghọ ọgwụ na-egbochi CPMySes (dịka CPB3A4, Cyp2c9) ma tụọ ihe egwu DDI. Na-eduzi nyocha nke na-egbochi nsogbu iji nyochaa nsonaazụ ọgwụ ọjọọ na ọrụ UGT. Chọpụta mmetụta nke ọgwụ ọjọọ na CP / UGT site na nyocha Hepatocytes.

Mmepe nke usoro nyocha nyocha: ọmụmụ CPM na UGT enzymes na-arụ ọrụ dị oke egwu na mmepe metaanalytical usoro yana ọmụmụ ọgwụ (DMPK). Jiri ihe omumu di iche-iche nke oma (di ka bile na plasma) maka matrik mmetụta nyocha, na-ebulikwa ihe mgbochi / nke nkwalite.

Nnyocha nke mkpụrụ ndụ ihe nketa polyymorphis: Ugt1A1 na mkpụrụ ndụ ihe ndị ọzọ na-achịkwa UGT enzyme dị mkpa nke dị mkpa ọgụgụ mkpụrụ ndụ ihe ndị dị mkpa. Site na mmepe nke Proforgenomimis, achoputala ya na onodu ihe nketa ha nke Metabolism, nke na - emetuta ihe ahu, mmepe na ogwu oria na otutu uzo ndi ozo.

Ọmụmụ banyere ọdịiche dị n'etiti ọdịiche dị na CPENTE na-arụ ọrụ dị ka mmadụ, oke, na nkịta na-ebuli usoro mgbanwe site na iji ọgwụ.

• Enzyme mgbochi

CPBE ENBYEE mebereenzyme mgbochiNa-ezo aka na phenomenon ebe ụfọdụ ogige nwere ike igbochi metabolism ụfọdụ, nke na-ebute oke nke ọgwụ ọjọọ, ma na-abawanye na ngwakọta, na-esite na-eweta ihe nchekwa nchekwa. Dabere na usoro mgbochi dị iche iche, mmetụta nke ọgwụ ọjọọ na CPB450 enzymes nwere ike kewaa mgbochi nje na oge - mgbochi dabere na ya (TDI dabere (tdi). Ihe mgbochi na-agbanwe agbanwe, nke a makwaara dị ka ihe mgbochi na-enweghị isi, n'ozuzu ya na-ezo aka na nguzobe nke ọgwụ ọgwụ na agbụ a na-ahụ maka agbụ, na-ebute inzyme na-agbanwe agbanwe. Mmetụta inhibitotor nke inhibitor na enzyme ahụ anaghị apụ n'anya mgbe a na-ewepụ ya, kama na-egosipụta oge - njirimara ndị dabere.

• CPL450 enzyme metabolicyping phenotpeng ọmụmụ ihe

Ka ọ dị ugbu a, enwere ụzọ atọ maka ịchọpụta enzyme metabolic pyp450: usoro nhọrọ nhọrọ, na-ekwupụta usoro nke 120050 nke mmadụ, na usoro nyocha. Enwere ike ekenye usoro mgbochi site na usoro mgbochi kemịkal na usoro mgbochi mgbochi antibud. Ọ na-agụnye arụmọrụ metabolic nke ọgwụ ime mmụọ na-enweghị mgbakwunye nke usoro ọgwụ CPP450 enzyme metabolic phenotpe. N'etiti ha, a na-ejikarị ụzọ mgbochi ọgwụ eme ihe n'ihi ọrụ ya dị mfe na ọnụ ala dị ala.

• Mmechi

CPNYMY enzymes na Ugt enzymes, dịka isi enzyme nke Metabolism ọgwụ, na-achịkwa oge m (oxiding), na-emetụta oke nrụpụta, na-emetụta oke ọgwụ, yana iji ọgwụ mee ihe. SubTYPE dịka CPP3A4 na CPB2D6, yana enzymes dịka Ugt1A1 na Ugt2B7, na-etolite netwọkụ metabolic dị mgbagwoju anya. Enwere ike ị nweta ọdịiche nke ihe omume ha (dịka Geney polyymorphism na ụdị Hepatocytes na LC - teknụzụ MS / MS / MS / Inye nkwado data maka mmepe ọgwụ.

Nrutuaka

Zhang, M., rottschä., V., & cm de linge, e. (2024). Mmetụta ọ ga-emetụta CPET na Ugt - metabolizing enzymes na ụbụrụ na-elekwasị anya na mkpughe ọgwụ ọjọọ. Nyocha Metabolism, 56(1), 1 - 30.

Ghosal, A., Ramanathan, R., Kishnani, N. S., Alton, 2005). Cytochrome P450 (CP) na UDP - Akwukwo Nso nke Metabolism, Polymorphism, na njirimara ha na Metabolism ọgwụ. N'ime Ọganihu na nyocha ọgwụ na nyocha (Volu. 6, PP. 295 - 336). Elsier.