Evolution of glutamate dehydrogenase regulation of insulin homeostasis is an example of molecular exaptation

Aron Allen, Jae Kwagh, Jie Fang, Charles A. Stanley, Thomas Smith

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 β cells with insulin homeostasis in mammals.

Original languageEnglish (US)
Pages (from-to)14431-14443
Number of pages13
JournalBiochemistry
Volume43
Issue number45
DOIs
StatePublished - Nov 16 2004
Externally publishedYes

Fingerprint

Glutamate Dehydrogenase
Allosteric Regulation
Homeostasis
Fatty Acids
Insulin
Antennas
Glutamic Acid
Mammals
Fungi
Deamination
Essential Fatty Acids
Peroxisomes
Glutamine
Mutagenesis
Organelles
Mitochondria
Bacteria
Amino Acids
Enzymes
Oxidation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Evolution of glutamate dehydrogenase regulation of insulin homeostasis is an example of molecular exaptation. / Allen, Aron; Kwagh, Jae; Fang, Jie; Stanley, Charles A.; Smith, Thomas.

In: Biochemistry, Vol. 43, No. 45, 16.11.2004, p. 14431-14443.

Research output: Contribution to journalArticle

Allen, Aron ; Kwagh, Jae ; Fang, Jie ; Stanley, Charles A. ; Smith, Thomas. / Evolution of glutamate dehydrogenase regulation of insulin homeostasis is an example of molecular exaptation. In: Biochemistry. 2004 ; Vol. 43, No. 45. pp. 14431-14443.
@article{6e82c1bcfc464ed9b0a334a30bb4c5e5,
title = "Evolution of glutamate dehydrogenase regulation of insulin homeostasis is an example of molecular exaptation",
abstract = "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 β cells with insulin homeostasis in mammals.",
author = "Aron Allen and Jae Kwagh and Jie Fang and Stanley, {Charles A.} and Thomas Smith",
year = "2004",
month = "11",
day = "16",
doi = "10.1021/bi048817i",
language = "English (US)",
volume = "43",
pages = "14431--14443",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "45",

}

TY - JOUR

T1 - Evolution of glutamate dehydrogenase regulation of insulin homeostasis is an example of molecular exaptation

AU - Allen, Aron

AU - Kwagh, Jae

AU - Fang, Jie

AU - Stanley, Charles A.

AU - Smith, Thomas

PY - 2004/11/16

Y1 - 2004/11/16

N2 - 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 β cells with insulin homeostasis in mammals.

AB - 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 β cells with insulin homeostasis in mammals.

UR - http://www.scopus.com/inward/record.url?scp=8544270914&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8544270914&partnerID=8YFLogxK

U2 - 10.1021/bi048817i

DO - 10.1021/bi048817i

M3 - Article

C2 - 15533048

AN - SCOPUS:8544270914

VL - 43

SP - 14431

EP - 14443

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 45

ER -