کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10537296 | 962709 | 2013 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inherent properties of adenylosuccinate lyase could explain S-Ado/SAICAr ratio due to homozygous R426H and R303C mutations
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
dl-dithiothreitolHPLC–ECSuccinyladenosineAdenylosuccinate lyase deficiencyADSLisopropyl-β-d-thiogalactosideadenylosuccinate lyaseSAICARPMRAICARDTTIPTGAMPadenosine monophosphate - آدنوزین مونوفسفرهAmpicillin - آمپی سیلینEDTA - اتیلن دی آمین تترا استیک اسید sodium dodecyl sulfate-polyacrylamide gel electrophoresis - الکتروفورز ژل دوده سولفات سدیم پلی آکریل آمیدSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدResource Sharing - به اشتراک گذاری منابعElectrochemical detection - تشخیص الکتروشیمیاییsAMP - سمپدوریاEnzyme kinetics - سینتیک آنزیمPsychomotor retardation - عقب ماندگی روانشناختیLuria-Bertani - لواریا بارتانیwild type - نوع وحشی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Adenylosuccinate lyase (ADSL) is a homotetrameric enzyme involved in the de novo purine biosynthesis pathway and purine nucleotide cycle. Missense mutations in the protein lead to ADSL deficiency, an inborn error of purine metabolism characterized by neurological and physiological symptoms. ADSL deficiency is biochemically diagnosed by elevated levels of succinylaminoimidazolecarboxamide riboside (SAICAr) and succinyladenosine (S-Ado), the dephosphorylated derivatives of the substrates. S-Ado/SAICAr ratios have been associated with three phenotypic groups. Different hypotheses to explain these ratios have been proposed. Recent studies have focused on measuring activity on the substrates independently. However, it is important to examine mixtures of the substrates to determine if mutations affect enzyme activity on both substrates similarly in these conditions. The two substrates may experience an indirect communication due to being acted upon by the same enzyme, altering their activities from the non-competitive case. In this study, we investigate this hidden coupling between the two substrates. We chose two mutations that represent extremes of the phenotype, R426H and R303C. We describe a novel electrochemical-detection method of measuring the kinetic activity of ADSL in solution with its two substrates at varying concentration ratios. Furthermore, we develop an enzyme kinetic model to predict substrate activity from a given ratio of substrate concentrations. Our findings indicate a non-linear dependence of the activities on the substrate ratios due to competitive binding, distinct differences in the behaviors of the different mutations, and S-Ado/SAICAr ratios in patients could be explained by inherent properties of the mutant enzyme.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1834, Issue 8, August 2013, Pages 1545-1553
Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1834, Issue 8, August 2013, Pages 1545-1553
نویسندگان
Stephen P. Ray, Nathan Duval, Terry G. II, Sean E. Shaheen, Kingshuk Ghosh, David Patterson,