Untangling the glutamate dehydrogenase allosteric nightmare.
Glutamate dehydrogenase (GDH) is found in all living organisms, but only animal GDH is regulated by a large repertoire of metabolites. More than 50 years of research to better understand the mechanism and role of this allosteric network has been frustrated by its sheer complexity. However, recent studies have begun to tease out how and why this complex behavior evolved. Much of GDH regulation probably occurs by controlling a complex ballet of motion necessary for catalytic turnover and has evolved concomitantly with a long antenna-like feature of the structure of the enzyme. Ciliates, the 'missing link' in GDH evolution, might have created the antenna to accommodate changing organelle functions and was refined in humans to, at least in part, link amino acid catabolism with insulin secretion.
Smith
Thomas J
TJ
Donald Danforth Plant Science Center, Saint Louis, MO 63132, USA. tsmith@danforthcenter.org
Stanley
Charles A
CA
D000494:Allosteric Regulation / Q000235:genetics; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D016798:Ciliophora / Q000201:enzymology; D004789:Enzyme Activation; D019143:Evolution, Molecular; D005969:Glutamate Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008958:Models, Molecular
D007328:Insulin; D002392:Catechin; C045651:epigallocatechin gallate; D005969:Glutamate Dehydrogenase