Glutaminase

Function

Glutaminase (GLN) catalyzes the conversion of glutamine (Gln) to glutamic acid (Glu). GLN is present at the axonal termini of neurons where GA functions as a neurotransmitter. ADP is an activator of GLN. GLN is a homodimer^[1]. In human GLN is found as 2 isozymes – GLN and GLN 2.

K-GLN is the kidney isoform
L-GLN is the liver isoform.
Glutaminase-asparaginase (GLN-ASN) can amidohydrolase both glutamine and asparagine to their corresponding Glu and Asp^[2]. For details on GLN-ASN see Glutaminase-Asparaginase (Pseudomonas 7A).

Relevance

Cancer cells show elevated GLN activity^[3]. Hepatic GLN increases during starvation, diabetes and feeding a high protein diet while kidney-type GLN increases in kidney during metabolic acidosis^[4].

Structural highlights

The glutamate binding site is in the helical domain of GLN and ^[5]. .

3D structures of glutaminase

Glutaminase 3D structures

ReferencesReferences

↑ Curthoys NP. Role of mitochondrial glutaminase in rat renal glutamine metabolism. J Nutr. 2001 Sep;131(9 Suppl):2491S-5S; discussion 2496S-7S. PMID:11533299
↑ Steckel J, Roberts J, Philips FS, Chou TC. Kinetic properties and inhibition of Acinetobacter glutaminase-asparaginase. Biochem Pharmacol. 1983 Mar 15;32(6):971-7. PMID:6838661
↑ Erickson JW, Cerione RA. Glutaminase: a hot spot for regulation of cancer cell metabolism? Oncotarget. 2010 Dec;1(8):734-40. PMID:21234284 doi:http://dx.doi.org/10.18632/oncotarget.208
↑ Curthoys NP, Watford M. Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr. 1995;15:133-59. PMID:8527215 doi:http://dx.doi.org/10.1146/annurev.nu.15.070195.001025
↑ Delabarre B, Gross S, Fang C, Gao Y, Jha A, Jiang F, Song J J, Wei W, Hurov JB. Full-Length Human Glutaminase in Complex with an Allosteric Inhibitor. Biochemistry. 2011 Nov 18. PMID:22049910 doi:10.1021/bi201613d

Created with the participation of Lindsey Butler.

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Alexander Berchansky, Michal Harel, Joel L. Sussman

[1] Curthoys NP. Role of mitochondrial glutaminase in rat renal glutamine metabolism. J Nutr. 2001 Sep;131(9 Suppl):2491S-5S; discussion 2496S-7S. PMID:11533299

[2] Steckel J, Roberts J, Philips FS, Chou TC. Kinetic properties and inhibition of Acinetobacter glutaminase-asparaginase. Biochem Pharmacol. 1983 Mar 15;32(6):971-7. PMID:6838661

[3] Erickson JW, Cerione RA. Glutaminase: a hot spot for regulation of cancer cell metabolism? Oncotarget. 2010 Dec;1(8):734-40. PMID:21234284 doi:http://dx.doi.org/10.18632/oncotarget.208

[4] Curthoys NP, Watford M. Regulation of glutaminase activity and glutamine metabolism. Annu Rev Nutr. 1995;15:133-59. PMID:8527215 doi:http://dx.doi.org/10.1146/annurev.nu.15.070195.001025

[5] Delabarre B, Gross S, Fang C, Gao Y, Jha A, Jiang F, Song J J, Wei W, Hurov JB. Full-Length Human Glutaminase in Complex with an Allosteric Inhibitor. Biochemistry. 2011 Nov 18. PMID:22049910 doi:10.1021/bi201613d

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Glutaminase

Contents

Function

Relevance

Structural highlights

3D structures of glutaminase

ReferencesReferences

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Glutaminase

Function

Relevance

Structural highlights

3D structures of glutaminase

ReferencesReferences

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