text: Discovery of acetyl-coenzyme A carboxylase 2 inhibitors: comparison of a fluorescence intensity-based phosphate assay and a fluorescence polarization-based ADP Assay for high-throughput screening.
  Acetyl-coenzyme A carboxylase (ACC) enzymes exist as two isoforms, ACC1 and ACC2, which play critical roles in fatty acid biosynthesis and oxidation. Though each isoform differs in tissue and subcellular localization, both catalyze the biotin- and ATP-dependent carboxylation of acetyl-coenzyme A to generate malonyl-coenzyme A, a key metabolite in the control of fatty acid synthesis and oxidation. The cytosolic ACC1 is expressed primarily in liver and adipose tissue, and uses malonyl-coenzyme A as a key building block in fatty acid biosynthesis. The mitochondrial ACC2 is primarily expressed in heart and skeletal muscle, where it is involved in the regulation of fatty acid oxidation. Inhibitors of ACC enzymes may therefore be useful therapeutics for diabetes, obesity, and metabolic syndrome. Two assay formats for these ATP-utilizing enzymes amenable to high-throughput screening are compared: a fluorescence intensity-based assay to detect inorganic phosphate and a fluorescence polarization-based assay to detect ADP. Acetyl-coenzyme A carboxylase inhibitors were identified by these high-throughput screening methods and were confirmed in a radiometric high performance liquid chromatography assay of malonyl-coenzyme A production.
entities.id: T10 T11 T12 T13 T14 T15 T16 T17 T18 T19 T1 T20 T21 T22 T23 T24 T25 T26 T27 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N CHEMICAL GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: fatty acid malonyl-coenzyme A fatty acid fatty acid ATP inorganic phosphate phosphate acetyl-coenzyme A ADP Acetyl-coenzyme A carboxylase Acetyl-coenzyme A Acetyl-coenzyme A carboxylase ACC ACC1 ACC2 ACC1 ACC ACC2 acetyl-coenzyme A carboxylase 2 ADP Acetyl-coenzyme A fatty acid malonyl-coenzyme A biotin ATP acetyl-coenzyme A malonyl-coenzyme A