| The structure and allosteric regulation of glutamate dehydrogenase. | |
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MedLine Citation:
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PMID: 21070828 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Glutamate dehydrogenase (GDH) has been extensively studied for more than 50 years. Of particular interest is the fact that, while considered by most to be a 'housekeeping' enzyme, the animal form of GDH is heavily regulated by a wide array of allosteric effectors and exhibits extensive inter-subunit communication. While the chemical mechanism for GDH has remained unchanged through epochs of evolution, it was not clear how or why animals needed to evolve such a finely tuned form of this enzyme. As reviewed here, recent studies have begun to elucidate these issues. Allosteric regulation first appears in the Ciliates and may have arisen to accommodate evolutionary changes in organelle function. The occurrence of allosteric regulation appears to be coincident with the formation of an 'antenna' like feature rising off the tops of the subunits that may be necessary to facilitate regulation. In animals, this regulation further evolved as GDH became integrated into a number of other regulatory pathways. In particular, mutations in GDH that abrogate GTP inhibition result in dangerously high serum levels of insulin and ammonium. Therefore, allosteric regulation of GDH plays an important role in insulin homeostasis. Finally, several compounds have been identified that block GDH-mediated insulin secretion that may be to not only find use in treating these insulin disorders but to kill tumors that require glutamine metabolism for cellular energy. |
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Authors:
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Ming Li; Changhong Li; Aron Allen; Charles A Stanley; Thomas J Smith |
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Publication Detail:
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Type: Journal Article Date: 2010-11-09 |
Journal Detail:
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Title: Neurochemistry international Volume: 59 ISSN: 1872-9754 ISO Abbreviation: Neurochem. Int. Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-08-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8006959 Medline TA: Neurochem Int Country: England |
Other Details:
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Languages: eng Pagination: 445-55 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Donald Danforth Plant Science Center, 975 North Warson Road, Saint Louis, MO 63132, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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