کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1358320 981335 2013 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effect of sulfonamides as carbonic anhydrase VA and VB inhibitors on mitochondrial metabolic energy conversion
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Effect of sulfonamides as carbonic anhydrase VA and VB inhibitors on mitochondrial metabolic energy conversion
چکیده انگلیسی

Obesity is quickly becoming an increasing problem in the developed world. One of the major fundamental causes of obesity and diabetes is mitochondria dysfunction due to faulty metabolic pathways which alter the metabolic substrate flux resulting in the development of these diseases. This paper examines the role of mitochondrial carbonic anhydrase (CA) isozymes in the metabolism of pyruvate, acetate, and succinate when specific isozyme inhibitors are present. Using a sensitive electrochemical approach of wired mitochondria to analytically measure metabolic energy conversion, we determine the resulting metabolic difference after addition of an inhibitory compound. We found that certain sulfonamide analogues displayed broad spectrum inhibition of metabolism, where others only had significant effect on some metabolic pathways. Pyruvate metabolism always displayed the most dramatically affected metabolism by the sulfonamides followed by fatty acid metabolism, and then finally succinate metabolism. This allows for the possibility of using designed sulfonamide analogues to target specific mitochondrial CA isozymes in order to subtly shift metabolism and glucogenesis flux to treat obesity and diabetes.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 6, 15 March 2013, Pages 1544–1548
نویسندگان
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