【생물학】 시토크롬 P450

시토크롬 P450(cytochrome P450, CYP)

 

추천글 : 【생물학】 1-2강. 생체고분자 라이브러리 

---

1. 개요 [본문]

2. 시토크롬 P450의 서브 그룹 [본문]

---

 

1. 개요 [목차]

⑴ 구조 및 기능

① 헴(heme) 단백질

② 아미노산 서열 : 511개의 아미노산으로 구성

 

MVPSFLSLSF SSLGLWASGL ILVLGFLKLI HLLLRRQTLA KAMDKFPGPP THWLFGHALE IQETGSLDKV VSWAHQFPYA HPLWFGQFIG FLNIYEPDYA 
KAVYSRGDPK APDVYDFFLQ WIGRGLLVLE GPKWLQHRKL LTPGFHYDVL KPYVAVFTES TRIMLDKWEE KAREGKSFDI FCDVGHMALN TLMKCTFGRG 
DTGLGHRDSS YYLAVSDLTL LMQQRLVSFQ YHNDFIYWLT PHGRRFLRAC QVAHDHTDQV IRERKAALQD EKVRKKIQNR RHLDFLDILL GARDEDDIKL 
SDADLRAEVD TFMFEGHDTT TSGISWFLYC MALYPEHQHR CREEVREILG DQDFFQWDDL GKMTYLTMCI KESFRLYPPV PQVYRQLSKP VTFVDGRSLP 
AGSLISMHIY ALHRNSAVWP DPEVFDSLRF STENASKRHP FAFMPFSAGP RNCIGQQFAM SEMKVVTAMC LLRFEFSLDP SRLPIKMPQL VLRSKNGFHL 
HLKPLGPGSG K

 

③ AlphaFold2로 예측한 시토크롬 p450 구조

 

Figure. 1. 시토크롬 P450의 2D 구조

 

 

 

Figure. 2. 시토크롬 p450의 3D 구조

 

④ 450 nm에서 흡광을 가지기 때문에 P450이라는 이름이 붙음

⑤ CYP는 mono-oxygenase system에서 산화효소로 기능함

⑥ P450 reductase(NADPH-dependent cytochrome P450 reductase)에 의해 CYP가 환원돼 활성화됨

⑵ 중요성

① 역할 1. clearance에서 상당한 역할을 함

○ 즉, cytochrome p450-mediated clearance : 55%

○ (참고) unchanged drug (i.e., non-metabolic clearance) : 25%

○ (참고) others : 20%

② 역할 2. metabolism에서 상당한 역할을 함

○ oxidation, reduction 등의 산화환원 반응의 경우 CYP가 90%를 담당함

⑶ CYP inhibition study 

⑷ CYP induction study 

 

 

2. 시토크롬 P450의 서브 그룹 [목차]

⑴ CYP1A2

① subtrates : caffeine, imipramine, tacrine, theophylline, R-warfarin

② inhibitors : ciprofloxacin, furafylline, mibefradil, ticlopidine

③ inducers : insulin, omerprazole (cruciferous vegetables, char-grilled meat, tobacco)

⑵ CYP2B6

① subtrates : bupropion, midazolam, tamoxifen, verapamil, testosterone

② inhibitors : ketoconazole, tranylcypromine, troglitazone, orphenadrine

③ inducers : dexamethasone, phenobarbital, rifampin, sodium, valproate

⑶ CYP2C9 

① subtrates : diclofenac, losarten, phenytoin, tolbutamide, S-warfarin

② inhibitors : fluconazole, isoniazid, sulfaphenazole, paroxetine

③ inducers : rifampin, secobarbital

⑷ CYP2C19

① subtrates : obeprazole, phenytoin, indomethacin, R-warfarin 

② inhibitors : cimetidine, ketoconazole, paroxetine, ticlopidine

③ inducers : prednisone, rifampin

⑸ CYP2D6

① subtrates : bufuralol, codeine, desipramine, lidocaine

② inhibitors : quinidine, methadone, cimetidine, fluoxetine

③ inducers : none identified

⑹ CYP2E1

① subtrates : acetaminophen, ethanol, chlozoxazone, sevoflurane

② inhibitors : disulfiram

③ inducers : ethanol, isoniazid (starvation)

⑺ CYP3A4 

① subtrates : nifedipine, erythromycin, midazolam, testosterone

② inhibitors : ketoconazole, erthyromycin, grapefruid juice, ritonavir

③ inducers : carbamazepine, phenobarbital, phenytoin, rifampin

 

입력: 2020.08.12 11:26