A tale of two glutaminases: homologous enzymes with distinct roles in tumorigenesis

Future Medicinal Chemistry
William P KattRichard A Cerione

Abstract

Many cancer cells exhibit an altered metabolic phenotype, in which glutamine consumption is upregulated relative to healthy cells. This metabolic reprogramming often depends upon mitochondrial glutaminase activity, which converts glutamine to glutamate, a key precursor for biosynthetic and bioenergetic processes. Two isozymes of glutaminase exist, a kidney-type (GLS) and a liver-type enzyme (GLS2 or LGA). While a majority of studies have focused on GLS, here we summarize key findings on both glutaminases, describing their structure and function, their roles in cancer and pharmacological approaches to inhibiting their activities.

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Methods Mentioned

BETA
x-ray scattering
x-ray crystallography
GAM
electrophoresis
light scattering
immunoprecipitation
transfection
xenografts
deamidation

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