Benzothiophene Carboxylate Derivatives as Novel Allosteric Inhibitors of Branched-chain α-Ketoacid Dehydrogenase Kinase
نویسندگان
چکیده
منابع مشابه
Structure-based design and mechanisms of allosteric inhibitors for mitochondrial branched-chain α-ketoacid dehydrogenase kinase.
The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are elevated in maple syrup urine disease, heart failure, obesity, and type 2 diabetes. BCAA homeostasis is controlled by the mitochondrial branched-chain α-ketoacid dehydrogenase complex (BCKDC), which is negatively regulated by the specific BCKD kinase (BDK). Here, we used structure-based design to develop a BDK inhibitor,...
متن کاملHuman Mutations Affecting Branched Chain Α -ketoacid Dehydrogenase
Maple syrup urine disease results from defective function of the branched chain α-ketoacid dehydrogenase complex [BCKD] within the matrix of the mitochondria. This disorder in humans is inherited as an autosomal recessive trait with an incidence of 1 in 150,000 live-births in the general population and 1/176 for the Mennonite population. Over 50 different causal mutations are known to exist sca...
متن کاملAmino acid deprivation induces translation of branched-chain alpha-ketoacid dehydrogenase kinase.
Leucine, isoleucine, and valine are used by cells for protein synthesis or are catabolized into sources for glucose and lipid production. These branched-chain amino acids influence proteolysis, hormone release, and cell cycle progression along with their other metabolic roles. The branched-chain amino acids play a central role in regulating cellular protein turnover by reducing autophagy. These...
متن کاملInsulin increases branched-chain -ketoacid dehydrogenase kinase expression in Clone 9 rat cells
Nellis, Mary M., Christopher B. Doering, Andrea Kasinski, and Dean J. Danner. Insulin increases branchedchain -ketoacid dehydrogenase kinase expression in Clone 9 rat cells. Am J Physiol Endocrinol Metab 283: E853–E860, 2002. First published June 3, 2002; 10.1152/ajpendo.00133.2002.— The branched-chain amino acids (BCAA) are committed to catabolism by the activity of the branched-chain -ketoaci...
متن کاملDifferential regulation of branched-chain -ketoacid dehydrogenase kinase expression by glucocorticoids and acidification in LLC-PK1-GR101 cells
Wang, Xiaonan, and S. Russ Price. Differential regulation of branched-chain -ketoacid dehydrogenase kinase expression by glucocorticoids and acidification in LLC-PK1-GR101 cells. Am J Physiol Renal Physiol 286: F504–F508, 2004. First published November 11, 2003; 10.1152/ajprenal.00296.2003.—Acidosis and glucocorticoids (GC) are two catabolic signals associated with chronic renal disease. Previo...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2014
ISSN: 0021-9258
DOI: 10.1074/jbc.m114.569251