کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10767972 | 1050802 | 2005 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Human CYP1A1 variants lead to differential eicosapentaenoic acid metabolite patterns
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
CYP1A1epoxyeicosatetraenoic acid - اسید اپوکسییکواستاترونیکEicosapentaenoic acid - اسید ایکوزاپنتانوئیکhydroxyeicosapentaenoic acid - اسید هیدروکسی ایکوزاپنتانوئیکPolyunsaturated fatty acid - اسید چرب غیر اشباعcytochrome P450 1A1 - سیتوکروم P450 1A1Pharmacogenetics - فارماکوژنتیکGenetic polymorphism - پلیمورفیسم ژنتیکی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Human CYP1A1 variants lead to differential eicosapentaenoic acid metabolite patterns Human CYP1A1 variants lead to differential eicosapentaenoic acid metabolite patterns](/preview/png/10767972.png)
چکیده انگلیسی
To answer the question whether the most common allelic variants of human CYP1A1, namely CYP1A1.1 (wild type), CYP1A1.2 (Ile462Val), and CYP1A1.4 (Thr461Asn), differ in their catalytic activity towards eicosapentaenoic acid (EPA), in vitro enzymatic assays were performed in reconstituted CYP1A1 systems. All CYP1A1 variants catalyzed EPA epoxygenation and hydroxylation to 17(R),18(S)-epoxyeicosatetraenoic acid (17(R),18(S)-EETeTr) and 19-OH-EPA, yet with varying catalytic efficiency and distinct regiospecificity. CYP1A1.1 and CYP1A1.4 formed 17(R),18(S)-EETeTr as main product (Km = 53 and 50 μM; Vmax = 0.60 and 0.50 pmol/min/pmol; Vmax/Km = 0.11 and 0.10 μMâ1 minâ1, respectively), followed by 19-OH-EPA (Km = 76 and 93 μM; Vmax = 0.37 and 0.37 pmol/min/pmol; Vmax/Km = 0.005 and 0.004 μMâ1 minâ1, respectively). The variant CYP1A1.2 produced almost equal amounts of both metabolites, but its catalytic efficiency for hydroxylation was five times higher (Km = 66 μM; Vmax = 1.7 pmol/min/pmol; Vmax/Km = 0.026 μMâ1 minâ1) and that for epoxygenation was twice higher (Km = 66 μM; Vmax = 1.5 pmol/min/pmol; Vmax/Km = 0.023 μMâ1 minâ1) than those of the wild-type enzyme. Thus, the Ile462Val polymorphism in human CYP1A1 affects EPA metabolism and may contribute to interindividual variance in the local production of physiologically active fatty acid metabolites in the cardiovascular system and other extrahepatic tissues, where CYP1A1 is expressed or induced by polycyclic aromatic hydrocarbons and other xenobiotics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 336, Issue 3, 28 October 2005, Pages 779-783
Journal: Biochemical and Biophysical Research Communications - Volume 336, Issue 3, 28 October 2005, Pages 779-783
نویسندگان
Dieter Schwarz, Pyotr Kisselev, Alexey Chernogolov, Wolf-Hagen Schunck, Ivar Roots,