Serine is a non-essential amino acid and a natural ligand and allosteric activator of pyruvate kinase M2.
The non-essential amino acid serine supports several metabolic processes that are crucial for the growth and survival of proliferating cells, including protein, amino acid and glutathione synthesis. As an important one-carbon donor to the folate cycle, serine contributes to nucleotide synthesis, methylation reactions and the generation of NADPH for antioxidant defence[2]. Serine activates recombinant PKM2 with a half maximal activation concentration (AC50) of 1.3 mM. Isothermal titration calorimetry was used to determine the dissociation constant (Kd) of the PKM2-serine interaction as 0.20 mM. Serine can bind to and activate human PKM2 and that following serine deprivation, PKM2 activity in cells is reduced. This reduction in PKM2 activity shifts cells to a fuel-efficient mode where more pyruvate is diverted to the mitochondria and more glucose derived carbon is channelled into serine biosynthesis to support cell proliferation[1].
[1] Chaneton B, et al. Nature. 2012, 491(7424):458-462. [2] Yang M, et al. Nat Rev Cancer. 2016, 16(10):650-62.