cyp2c19

cyp2c19

CYP2C19是CYP450酶第二亞家族中的重要成員，是人體重要的藥物代謝酶，在肝臟中有很多表達。CYP2C19基因座位於染色體區10q24.2上，都由9個外顯子構成。CYP2C19與CYP2C9有92%的序列同源性。

目錄

1重要性 2多態性

重要性

在2002年最多常用的200種處方藥物中，大部分由P450酶負責代謝。而P450酶負責代謝的藥物中，12%由CYP2C19代謝。由CYP2C19代謝的藥物如下。

Drugs and other agents whose metabolic pathway cosegregates with the activity ofcytochrome P450 2C19invitroand/orin vivo

Proton pump inhibitors

Omeprazole 5-hydroxylation;Lansoprazole 5-hydroxylation;

Pantoprazole O-demethylation;Rabeprazole N-demethylation

Anticonvulsants, hypnosedatives, muscle relaxants

Phenytoin 3’- and 4’-hydroxylation;( S)-Mephenytoin and nirvanol 4′-hydroxylation;Methylphenytoin 4′-hydroxylation;Diazepam N-demethylation (activation);Desmethyldiazepam hydroxylation;Flunitrazepam N-demethylation;

Phenobarbital p-hydroxylation;( R)-Hexobarbital 3′-hydroxylation;

( R)-Mephobarbital 4-hydroxylation;Carisoprodol N-demethylation

Anti-infectives

Proguanil cyclisation (activation); Chlorproguanil cyclisation (activation);

Nelfinavir hydroxylation (activation)

Antidepressants

Citalopram N-demethylation; Fluoxetine N-demethylation; Sertraline N-demethylation; Venlafaxine O-demethylation (activation); Imipramine N-demethylation; Clomipramine N-demethylation; Trimipramine; Amitriptyline N-demethylation; Nortriptyline demethylation; Moclobemide C-hydroxylation

Others (mainlyin vitroevidence)

Thioridazine

Propranolol side-chain oxidation

Tolbutamide 4-hydroxylation

( R)-Warfarin 8-hydroxylation

Progesterone 21-hydroxylation

Testosterone oxidation at 17-position

Desogestrel 3α-hydroxylation (activation)

Cyclophosphamide 4-hydroxylation (active)

Ifosfamide 4-hydroxylation (active)

Methoxychlor O-demethylation (activation)

多態性

CYP2C19具有很多SNP位點，在人類細胞色素P450等位基因命名法委員會（HumanCYPAllele NomenclatureCommittee）有詳盡的總結。最常見的是 CYP2C19*2和 CYP2C19*3。 CYP2C19*2會導致轉錄蛋白的剪切突變失活，而 CYP2C19*3能構成一個終止子，破壞轉錄蛋白的活性。據統計， CYP2C19*2和 CYP2C19*3兩個突變位點能解釋幾乎100%的東亞人和85%的高加索人種的相關弱代謝遺傳缺陷，而其他兩種等位基因C YP2C19* 4和 CYP2C19* 5主要在高加索人種中分佈。大量證據證實，不同人種在 CYP2C19的底物的代謝能力有很大差異；2–5%高加索人是弱代謝者，而13–23%的亞洲人是弱代謝者。這是一由於在亞洲人口中 CYP2C19* 2和 CYP2C19* 3等位基因的高頻率造成的。

目錄