作者: Ming Li , Changhong Li , Aron Allen , Charles A. Stanley , Thomas J. Smith
DOI: 10.1007/S11064-013-1173-2
关键词: Enzyme 、 Allosteric regulation 、 Leucine 、 Biochemistry 、 Glutamate dehydrogenase 、 GTP' 、 Amino acid 、 Oxidative deamination 、 Mutagenesis 、 Biology
摘要: Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate. Only in animal kingdom this heavily allosterically regulated by wide array metabolites. The major activators are ADP and leucine inhibitors include GTP, palmitoyl CoA, ATP. Spontaneous mutations GTP inhibitory site lead hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as why mammalian GDH so tightly regulated. Patients with HHS exhibit hypersecretion insulin upon consumption protein concomitantly extremely high levels ammonium serum. atomic structures four new complexed complexes identified three different allosteric binding sites. Using transgenic mouse model expressing human form GDH, at least these compounds blocked dysregulated pancreatic tissue. EGCG from green tea prevented hyper-response amino acids whole animals improved basal serum glucose levels. structure ECG–GDH complex mutagenesis studies directing structure-based drug design using polyphenols base scaffold. In addition, all elucidating mechanisms allostery enzyme.