Fig. 1: The serine synthesis pathway (SSP) and downstream anabolic pathways.
From: Can small molecular inhibitors that stop de novo serine synthesis be used in cancer treatment?
A Serine synthesis pathway. Serine is shown to be both imported from the extracellular space by amino acid exchangers and also synthesised de novo from glucose. The first rate-limiting enzyme, PHGDH, oxidises 3-phosphoglycerate (3-PG) using NAD + cofactor to produce phosphohydroxy pyruvate (P-Pyr); secondly, phosphoserine aminotransferase (PSAT1) transaminates P-Pyr to phosphoserine (P-Ser) using glutamate (Glu) as the nitrogen donor; lastly, phosphoserine phosphatase (PSPH) hydrolyses P-Ser to serine. Serine is directly incorporated into lipid head groups and proteins. Serine-derived glycine and folate one-carbon units contribute to nucleotide synthesis [adapted from 12]. B The role of serine in downstream anabolic pathways. Serine is a crucial contributor of one carbon units feeding into one carbon metabolism, the folate cycle and the methionine cycle. One-carbon units donated as a result of serine metabolism are used in the anabolic synthesis of cellular building blocks, co-factors and reducing factors. This figure shows the downstream anabolic pathways which use serine derivatives, and the cellular functions (red) which they support, such as biomolecule synthesis, maintenance of cellular homoeostasis, redox reactions and post-translational modifications.
