Phosphoglycerate Dehydrogenase: Potential Therapeutic Target and Putative Metabolic Oncogene

Figure 2

Schematic of the major pathways of serine metabolism in a mammalian liver. Shown in red, phosphoglycerate dehydrogenase, the first enzyme branching from glycolysis in a three-step serine biosynthetic pathway uses NAD⁺ as a cofactor to oxidize 3-phosphoglycerate into phosphohydroxypyruvate. The product is then subsequently converted into phosphoserine via transamination by phosphoserine aminotransferase and, ultimately, to serine via phosphate ester hydrolysis and the enzyme phosphoserine phosphatase. Classic work by Snell [16] suggests preferential upregulation of the serine hydroxymethyltransferase branch, leading to nucleic acid synthesis coupled with downregulation of the serine dehydratase and serine aminotransferase branches in some subsets of cancer cells, adapted from Snell [16].