Glutamine dependence is a prominent feature of
cancer metabolism, and here we show that
melanoma cells, irrespective of their oncogenic background, depend on
glutamine for growth. A quantitative audit of how
carbon from
glutamine is used showed that TCA-cycle-derived
glutamate is, in most
melanoma cells, the major
glutamine-derived cataplerotic output and product of glutaminolysis. In the absence of
glutamine, TCA cycle metabolites were liable to depletion through
aminotransferase-mediated α-ketoglutarate-to-
glutamate conversion and
glutamate secretion.
Aspartate was an essential cataplerotic output, as
melanoma cells demonstrated a limited capacity to salvage external
aspartate. Also, the absence of
asparagine increased the
glutamine requirement, pointing to vulnerability in the
aspartate-
asparagine biosynthetic pathway within
melanoma metabolism. In contrast to
melanoma cells, melanocytes could grow in the absence of
glutamine. Melanocytes use more
glutamine for
protein synthesis rather than secreting it as
glutamate and are less prone to loss of
glutamate and TCA cycle metabolites when starved of
glutamine.