ArticleProceedings of the National Academy of Sciences of the United States of America2015
Glycolytic flux controls D-serine synthesis through glyceraldehyde-3-phosphate dehydrogenase in astrocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
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- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Glucose metabolism and endometrium decidualization.Frontiers in endocrinology · 2025Review
- Emerging roles of astrocytes in hippocampal circuitry and behavior.Frontiers in cellular neuroscience · 2025Review
- Role of Glycolytic and Glutamine Metabolism Reprogramming on the Proliferation, Invasion, and Apoptosis Resistance through Modulation of Signaling Pathways in Glioblastoma.International journal of molecular sciences · 2023Review
- Perturbation of serine enantiomers homeostasis in the striatum of MPTP-lesioned monkeys and mice reflects the extent of dopaminergic midbrain degeneration.Neurobiology of disease · 2023Article
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- Selective Ablation ofThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- TKTL1 Knockdown Impairs Hypoxia-Induced Glucose-6-phosphate Dehydrogenase and Glyceraldehyde-3-phosphate Dehydrogenase Overexpression.International journal of molecular sciences · 2022Article
- Glucose metabolic crosstalk and regulation in brain function and diseases.Progress in neurobiology · 2021Review
- NMDARs, Coincidence Detectors of Astrocytic and Neuronal Activities.International journal of molecular sciences · 2021Review
- The sepsis induced defective aggravation of immune cells: a translational science underling chemico-biological interactions from altered bioenergetics and/or cellular metabolism to organ dysfunction.Molecular and cellular biochemistry · 2021Review
- Glycolytic Metabolism, Brain Resilience, and Alzheimer's Disease.Frontiers in neuroscience · 2021Review
- L-serine synthesis via the phosphorylated pathway in humans.Cellular and molecular life sciences : CMLS · 2020Review
- d-amino Acids in Health and Disease: A Focus on Cancer.Nutrients · 2019Review
- High Pressure Stress Response: Involvement of NMDA Receptor Subtypes and Molecular Markers.Frontiers in physiology · 2019Article
- Metabolomics Analysis in Serum from Patients with Colorectal Polyp and Colorectal Cancer byDisease markers · 2019Article
- The Energy Landscape of Human Serine Racemase.Frontiers in molecular biosciences · 2018Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
D-Serine is an essential coagonist with glutamate for stimulation of N-methyl-D-aspartate (NMDA) glutamate receptors. Although astrocytic metabolic processes are known to regulate synaptic glutamate levels, mechanisms that control D-serine levels are not well defined. Here we show that d-serine production in astrocytes is modulated by the interaction between the D-serine synthetic enzyme serine racemase (SRR) and a glycolytic enzyme, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). In primary cultured astrocytes, glycolysis activity was negatively correlated with D-serine level. We show that SRR interacts directly with GAPDH, and that activation of glycolysis augments this interaction. Biochemical assays using mutant forms of GAPDH with either reduced activity or reduced affinity to SRR revealed that GAPDH suppresses SRR activity by direct binding to GAPDH and through NADH, a product of GAPDH. NADH allosterically inhibits the activity of SRR by promoting the disassociation of ATP from SRR. Thus, astrocytic production of D-serine is modulated by glycolytic activity via interactions between GAPDH and SRR. We found that SRR is expressed in astrocytes in the subiculum of the human hippocampus, where neurons are known to be particularly vulnerable to loss of energy. Collectively, our findings suggest that astrocytic energy metabolism controls D-serine production, thereby influencing glutamatergic neurotransmission in the hippocampus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.