Dietary and pharmacological induction of serine synthesis genes

Abstract

There is an increasing interest in the pathway of L-serine synthesis and its. Although L-serine and downstream products can be obtained from the diet, serine deficiency has been documented in neurological disorders, macular degeneration and aging. This evidence calls for strategies to induce serine synthesis. Here I address this problem taking advantage of the wealth of data deposited in the gene expression omnibus database. I uncover that low protein and ketogenic diets increase the expression of serine synthesis genes in the liver and the brain relative to control diets. I discover oestrogen medications, the antifolate methotrexate and serine synthesis inhibitors as classes of compounds inducing the expression of serine synthesis genes in the liver. Future work is required to investigate the use of these interventions for the management of serine deficiency disorders.

Impact of Formate Supplementation on Body Weight and Plasma Amino Acids

“…The female mice in the cohorts investigated in this study were not pregnant, but they were in their reproductive age. It has been observed that molecules modulating oestrogen metabolism induce the expression of serine synthesis genes in the liver of male mice [ 22 ]. The underlying mechanism of this association is not clear yet.…”

“…Based on our data for female mice, formate supplementation lowers plasma amino acids. In turn, there is evidence that a low-protein diet induces the expression of genes from the serine synthesis and mitochondrial serine metabolism to glycine and formate in rat livers [ 22 ]. This increase at the gene expression level is reflected in an increase of plasma levels of serine and glycine [ 23 ], while formate was not quantified.…”

The Ketogenic Diet Revisited: Beyond Ketones

“…The KD has recently been shown to induce the expression of genes involved in the serine synthesis, such as PHGDH, in the liver and cerebral cortex of mice (57). The low content of proteins in the KD can result in amino acid stress and thereby induce serine (amino acid) synthesis as a feedback mechanism.…”

Ketogenic Diet Consumption Inhibited Mitochondrial One-Carbon Metabolism

“…On the other hand, ketogenesis may directly regulate SSP via the enzyme 3-phosphoglycerate dehydrogenase (PHGDH), the first step in the branching point from glycolysis to SSP. Ketogenic diets have been found to induce the expression of the SSP gene PHGDH in the liver and the cerebral cortex of mice [ 6 ], and such induction was proposed to assist the management of epilepsy by the ketogenic diet. The SSP contains an NAD+ dehydrogenase step catalyzed by PHGDH, and this pathway could contribute to NADH generation [ 7 ]; hence, we postulate that ketogenesis may modulate SSP ( Figure 1 ).…”