| Evolution of glutamate dehydrogenase regulation of insulin homeostasis is an example of molecular exaptation. | |
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MedLine Citation:
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PMID: 15533048 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glutamate dehydrogenase (GDH) is found in all organisms and catalyzes the oxidative deamination of glutamate to 2-oxoglutarate. While this enzyme does not exhibit allosteric regulation in plants, bacteria, or fungi, its activity is tightly controlled by a number of compounds in mammals. We have previously shown that this regulation plays an important role in insulin homeostasis in humans and evolved concomitantly with a 48-residue "antenna" structure. As shown here, the antenna and some of the allosteric regulation first appears in the Ciliates. This primitive regulation is mediated by fatty acids and likely reflects the gradual movement of fatty acid oxidation from the peroxisomes to the mitochondria as the Ciliates evolved away from plants, fungi, and other protists. Mutagenesis studies where the antenna is deleted support this contention by demonstrating that the antenna is essential for fatty acid regulation. When the antenna from the Ciliates is spliced onto human GDH, it was found to fully communicate all aspects of mammalian regulation. Therefore, we propose that glutamate dehydrogenase regulation of insulin secretion is a example of exaptation at the molecular level where the antenna and associated fatty acid regulation was created to accommodate the changes in organelle function in the Ciliates and then later used to link amino acid catabolism and/or regulation of intracellular glutamate/glutamine levels in the pancreatic beta cells with insulin homeostasis in mammals. |
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Authors:
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Aron Allen; Jae Kwagh; Jie Fang; Charles A Stanley; Thomas J Smith |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Biochemistry Volume: 43 ISSN: 0006-2960 ISO Abbreviation: Biochemistry Publication Date: 2004 Nov |
Date Detail:
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Created Date: 2004-11-09 Completed Date: 2005-01-11 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: United States |
Other Details:
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Languages: eng Pagination: 14431-43 Citation Subset: IM |
Affiliation:
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The Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, Missouri 63132, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Diphosphate
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analogs & derivatives*,
chemistry,
metabolism Alanine / genetics Allosteric Regulation / genetics Animals Arginine / genetics Cattle Deamination Evolution, Molecular* Glutamate Dehydrogenase / antagonists & inhibitors, chemistry*, genetics, metabolism Homeostasis* / genetics Humans Insulin / secretion* Kinetics Lipid Peroxidation Palmitoyl Coenzyme A / chemistry Protein Binding Sequence Alignment Sequence Homology, Amino Acid Substrate Specificity Tetrahymena thermophila / enzymology, genetics |
| Grant Support | |
ID/Acronym/Agency:
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DK53012/DK/NIDDK NIH HHS; GM10704/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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11061-68-0/Insulin; 1763-10-6/Palmitoyl Coenzyme A; 56-41-7/Alanine; 58-64-0/Adenosine Diphosphate; 74-79-3/Arginine; 84430-17-1/2',3'-(O-(2,4,6-trinitrocyclohexadienylidine))adenosine 5'-diphosphate; EC 1.4.1.2/Glutamate Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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