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L-Glutamine (Gln) - a conditionally essential amino acid - is the
most abundant free amino acid in human blood. As a source of carbon and
nitrogen, Gln supplies many intermediates required for multiple metabolic functions including, among others,
purine, pyrimidine, and glutathione synthesis pathways. In addition,
one of the important functions of Gln - once deaminated into Glutamate
by Glutaminase (Gls1 & Gls2) - is to
fuel the citric
acid cycle (TCA),
which represents a major energy-producing process, especially for
highly proliferating cells e.g. T lymphocytes and cancer cells. Hence,
because of the cohabitation of both cell types within tumors and the high
rate of tumoral glutaminolysis, immune cells are likely to be often deprived of Gln, a
condition which can severely limit their functions.
Given its pleiotropic role, targeting Gln metabolism thus represents an
attractive druggable therapeutic avenue in immuno-oncology. For instance, Gls1 can be directly targeted
through Glutaminase inhibitors such as CB-839 (under clinical
development in various type of cancers). Overall, assessing novel
therapeutic molecules aiming at restoring Gln level should rely, mainly,
on Gln quantification, which can now be addressed
by ELISA!
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