Glutaminolysis is the metabolic process through which glutamine, a non-essential amino acid, is catabolized to support cellular energy and biosynthesis. In many cancer cells, glutaminolysis is upregulated to meet the high demands for energy (ATP), biosynthetic precursors, and maintenance of redox balance.
Key Steps and Abbreviations in Glutaminolysis.
Glutamine (Gln): uptake of glutamine from the extracellular environment.
Glutaminase (GLS):Converts glutamine into glutamate by deamination. GLS overexpressed in cancers.
Glutamate (Glu): further converted into α-ketoglutarate (α-KG).
Glutamate Dehydrogenase (GDH): Catalyzes the conversion of glutamate to α-KG, feeding the tricarboxylic acid cycle (TCA, also known as Krebs cycle).
α-Ketoglutarate (α-KG):α-KG is a key intermediate in the TCA cycle.
Additional Players:
c-Myc: A transcription factor frequently overexpressed in cancer that upregulates genes involved in glutamine uptake and metabolism, including GLS.
SLC1A5 (ASCT2): A glutamine transporter that is often upregulated in cancer to facilitate increased glutamine uptake.
In many cancers there is an upregulation of key glutaminolysis components:GLS, SLC1A5, c-Myc.
Many studies have found that overexpression of glutaminolysis-related enzymes (especially GLS) correlates with aggressive tumor behavior and poor patient outcomes.
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