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Multiple enzymes involved in glutamine metabolism

Molecular classification
Enzyme, Transporter (in the context of transporters critical to glutamine metabolism, e.g., ASCT2)
01

Overview

Multiple enzymes involved in glutamine metabolism constitute a metabolic network responsible for the uptake, catabolism, and utilization of glutamine, a central amino acid in cellular metabolism. Key enzymes in this pathway include amino acid transporter ASCT2 (SLC1A5), which mediates cellular import of glutamine; glutaminase (GLS, with isoforms GLS1 and GLS2), which catalyzes the conversion of glutamine to glutamate; and glutamate dehydrogenase (GDH/GLUD1), which converts glutamate to α-ketoglutarate for entry into the tricarboxylic acid (TCA) cycle[1][3][7]. Additional enzymes, such as glutamine-fructose-6-phosphate transaminase (GFAT), CAD, and glutamine synthetase (GS), are also involved in branching reactions of nitrogen transport and nucleotide/amino acid biosynthesis[7]. Many cancers and highly proliferative cells show increased dependence on glutamine metabolism for energy, growth, and redox homeostasis, making several of these enzymes therapeutic targets[2][4][6]. Inhibitors have been developed against several major nodes (notably GLS and GDH), but targeting these enzymes must be done with care due to potential toxicity and the essential role of glutamine in normal tissues[2][6]. **Important Caveat:** The entry "Multiple enzymes involved in glutamine metabolism" is an umbrella term and not a single molecular target; rather, it refers to a group of distinct enzymes and transporters with related but separate structures, functions, and drug targeting properties. For structured or database use, individual protein names such as "Glutaminase (GLS)", "Glutamate dehydrogenase (GDH)", "Amino acid transporter ASCT2 (SLC1A5)", etc., should be entered separately for maximal specificity[2][3][1][7].

Other names
Glutamine metabolism-related enzymesglutaminolysis enzymesenzymes of glutamine catabolism
02

Mechanism of action

Enzyme inhibition (e.g., glutaminase inhibitors block conversion of glutamine to glutamate); Glutamine antimetabolite (irreversible competitive inhibition of multiple glutamine-utilizing enzymes); Systemic glutamine depletion (e.g., via L-asparaginase, phenylbutyrate)

03

Biological functions

Cellular metabolismEnergy production (TCA cycle anaplerosis)Nitrogen transportAmino acid synthesis and degradationRedox balanceCell proliferation
04

Disease associations

CancerNeurodegenerative diseaseCardiovascular diseaseMetabolic disordersImmune dysregulation
05

Safety considerations

Neurotoxicity (noted with glutamine antimetabolites like DON)Gastrointestinal toxicityMyelosuppression (bone marrow toxicity)Potential for broad metabolic disruption, as glutamine is essential for many physiological processesResistance via upregulation of de novo glutamine synthesis
06

Interacting drugs

CB-839 (telaglenastat)

8 more in the full profile.

07

Biomarkers

Expression of key glutamine metabolism enzymes (e.g., GLS1, GDH)Glutamine uptake or dependence signaturesMetabolomic profiling (e.g., glutamine or glutamate levels)RiskScore or molecular subtype based on glutamine metabolic gene expression (e.g., in LGG)

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