کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10832562 | 1065770 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Correction of a genetic deficiency in pantothenate kinase 1 using phosphopantothenate replacement therapy
ترجمه فارسی عنوان
اصلاح یک کمبود ژنتیکی در پانوتنات کیناز 1 با استفاده از جایگزینی فسفوپنتنات
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Coenzyme A (CoA) is a ubiquitous cofactor involved in numerous essential biochemical transformations, and along with its thioesters is a key regulator of intermediary metabolism. Pantothenate (vitamin B5) phosphorylation by pantothenate kinase (PanK) is thought to control the rate of CoA production. Pantothenate kinase associated neurodegeneration is a hereditary disease that arises from mutations that inactivate the human PANK2 gene. Aryl phosphoramidate phosphopantothenate derivatives were prepared to test the feasibility of using phosphopantothenate replacement therapy to bypass the genetic deficiency in the Pank1â/â mouse model. The efficacies of candidate compounds were first compared by measuring the ability to increase CoA levels in Pank1â/â mouse embryo fibroblasts. Administration of selected candidate compounds to Pank1â/â mice corrected their deficiency in hepatic CoA. The PanK bypass was confirmed by the incorporation of intact phosphopantothenate into CoA using triple-isotopically labeled compound. These results provide strong support for PanK as a master regulator of intracellular CoA and illustrate the feasibility of employing PanK bypass therapy to restore CoA levels in genetically deficient mice.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 116, Issue 4, December 2015, Pages 281-288
Journal: Molecular Genetics and Metabolism - Volume 116, Issue 4, December 2015, Pages 281-288
نویسندگان
Stephen P. Zano, Caroline Pate, Matthew Frank, Charles O. Rock, Suzanne Jackowski,