3-Phosphoglycerate Dehydrogenase, a Key Enzyme forl-Serine Biosynthesis, Is Preferentially Expressed in the Radial Glia/Astrocyte Lineage and Olfactory Ensheathing Glia in the Mouse Brain

  title={3-Phosphoglycerate Dehydrogenase, a Key Enzyme forl-Serine Biosynthesis, Is Preferentially Expressed in the Radial Glia/Astrocyte Lineage and Olfactory Ensheathing Glia in the Mouse Brain},
  author={Miwako Yamasaki and Keiko Yamada and Shigeki Furuya and Junya Mitoma and Yoshio Hirabayashi and Masahiko Watanabe},
  journal={The Journal of Neuroscience},
  pages={7691 - 7704}
l-Serine is synthesized from glycolytic intermediate 3-phosphoglycerate and is an indispensable precursor for the synthesis of proteins, membrane lipids, nucleotides, and neuroactive amino acids d-serine and glycine. We have recently shown that l-serine and its interconvertible glycine act as Bergmann glia-derived trophic factors for cerebellar Purkinje cells. To investigate whether such a metabolic neuron-glial relationship is fundamental to the developing and adult brain, we examined by in… 
Expression of l-Serine Biosynthetic Enzyme 3-Phosphoglycerate Dehydrogenase (Phgdh) and Neutral Amino Acid Transporter ASCT1 Following an Excitotoxic Lesion in the Mouse Hippocampus
It is hypothesized that the secretion of l-serine is regulated by astrocytes in response to toxic molecules such as glutamate and free radicals that promote neurodegeneration, and may correspond to the level of l -serine needed for neuronal survival and glial activation during brain insults.
Segmental and complementary expression of L-serine biosynthetic enzyme 3-phosphoglycerate dehydrogenase and neutral amino acid transporter ASCT1 in the mouse kidney.
The kidney was examined, and it was found that Phgdh was distributed highly in the renal papilla and inner layer of the outer zone and moderately in the cortex, suggesting that metabolic interplay mediated by L-serine biosynthesis and supply may exist in the kidney too.
Localization of 3-phosphoglycerate dehydrogenase, an enzyme involved in de novo L-serine biosynthesis, in the peripheral nervous system and non-neuronal tissues of mice
The cellular localization of 3-phosphoglycerate dehydrogenase (3PGDH), a key enzyme in L-serine production, in tissue outside the central nervous system of the mouse was examined by immunohistochemistry and in situ hybridization.
Neutral Amino Acid Transporter ASCT1 Is Preferentially Expressed in l-Ser-Synthetic/Storing Glial Cells in the Mouse Brain with Transient Expression in Developing Capillaries
Results strongly suggest that a large amount of l-Ser is synthesized and stored in these glial cells and is released through ASCT1 in exchange for other extracellular substrates, which appears to be regulated to meet metabolic demands by differentiating and mature neurons through the transport of glia- and blood-borne small neutral amino acids.
Novel neuroglial and glioglial relationships mediated by L-serine metabolism.
It is proposed that L-serine synthesis in these glial cells and its supply to nearby neurons and other glia constitute a novel metabolic unit in the brain.
An essential role for de novo biosynthesis of L-serine in CNS development.
  • S. Furuya
  • Biology
    Asia Pacific journal of clinical nutrition
  • 2008
The embryonic lethal phenotype of Phgdh knockouts indicates that L-serine must be synthesized endogenously in mouse (and probably humans) during embryonic development, highlighting the vital role of de novo L-Serine synthesis in the formation and function of the mammalian central nervous system.
Selective expression of L-serine synthetic enzyme 3PGDH in schwann cells, perineuronal glia, and endoneurial fibroblasts along rat sciatic nerves and its upregulation after crush injury.
The results suggest that in the peripheral nervous system, these non-neuronal cells synthesize and may supply L-serine to satisfy metabolic demands for maintenance and regeneration of peripheral nerves and for proliferation and activation of macrophages upon nerve injury.
L-serine synthesis via the phosphorylated pathway in humans
It is believed that an in-depth investigation of these enzymes is crucial to identify the molecular mechanisms involved in modulating concentrations of the serine enantiomers and for studying the interplay between glial and neuronal cells and also to determine the most suitable therapeutic approach for various diseases.
Cystathionine β‐synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS
Results suggest that CBS plays a crucial role in the development and maintenance of the CNS and that radial glia/astrocyte dysfunction might be involved in the complex neuropathological features associated with abnormal homocysteine metabolism.


Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission.
Cloning and expression of serine racemase in the brain demonstrates the conservation of D-amino acid metabolism in mammals with implications for the regulation of N-methyl-D-aspartate neurotransmission through glia-neuronal interactions.
Purification of serine racemase: biosynthesis of the neuromodulator D-serine.
Properties such as pH optimum, Km values, and the requirement for pyridoxal phosphate resemble those of bacterial racemases, suggesting that the biosynthetic pathway for D-amino acids is conserved from bacteria to mammalian brain.
Synthesis and release of L‐serine by rat astroglia‐rich primary cultures
The enzymes of the “phosphorylated pathway” of serine biosynthesis, i.e., 3‐phosphoglycerate dehydrogenase, phosphoserine aminotransferase andosphoserine phosphatase are present in rat brain as well as in rat astroglia‐rich primary cultures and their specific activities have been determined.
L-serine and glycine serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons.
It is demonstrated that l-serine (l-Ser) and glycine (Gly) also are glia-derived trophic factors that mediate the troPHic actions of glial cells on Purkinje neurons.
Occurrence of an Unusual Phospholipid, Phosphatidyl-l-threonine, in Cultured Hippocampal Neurons
Observations show that hippocampal neurons require exogenous l-serine for the synthesis of PS and sphingolipids in the absence of astroglial cells and suggested that astrogLial cells contribute to neuronal lipid synthesis through the supply ofl-Serine.
Enzymes of serine metabolism in normal, developing and neoplastic rat tissues.
  • K. Snell
  • Biology, Chemistry
    Advances in enzyme regulation
  • 1984
Acetoacetate and Glucose as Lipid Precursors and Energy Substrates in Primary Cultures of Astrocytes and Neurons from Mouse Cerebral Cortex
It is concluded that ketone bodies can be metabolized both by the glial cells and by the neuronal cells of developing mouse brain.
Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency--a neurometabolic disorder associated with reduced L-serine biosynthesis.
The data presented in this paper suggest an important role for PHGDH activity and L-serine biosynthesis in the metabolism, development, and function of the central nervous system.
Distinct Roles for Ceramide and Glucosylceramide at Different Stages of Neuronal Growth
It is shown that ceramide plays distinct roles at different stages of neuronal development, consistent with the possibility that minor process formation and apoptosis can be regulated by ceramide-dependent signaling pathways and that the decision whether to enter these diametrically opposed pathways depends on intracellular ceramide concentrations.
d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors
Compared the immunohistochemical localizations of d-serine, glycine, and NMDA receptors in rat brain, d-Serine seems to be the endogenous ligand of glycine sites in the telencephalon and developing cerebellum, whereas glycine predominates in the adult cere Bellum, olfactory bulb, and hindbrain.