Serine racemase: A glial enzyme synthesizing d -serine to regulate glutamate- N -methyl- d -aspartate neurotransmission
Open accessAbstract
Although d amino acids are prominent in bacteria, they generally are thought not to occur in mammals. Recently, high levels of d -serine have been found in mammalian brain where it activates glutamate/ N -methyl- d -aspartate receptors by interacting with the “glycine site” of the receptor. Because amino acid racemases are thought to be restricted to bacteria and insects, the origin of d -serine in mammals has been puzzling. We now report cloning and expression of serine racemase, an enzyme catalyzing the formation of d -serine from l -serine. Serine racemase is a protein representing an additional family of pyridoxal-5′ phosphate-dependent enzymes in eukaryotes. The enzyme is enriched in rat brain where it occurs in glial cells that possess high levels of d -serine in vivo . Occurrence 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.
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d-Serine crosses the blood-brain barrier by amino acid transporter solute carrier family 6 member 14.
“d-Serine serves as a neuromodulator and crosses the BBB by amino acid transporter solute carrier family 6 member 14 (refs. 31–35).”
From Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system (2025) · cites this paper as [32]
The Discussion describes D-serine as a modulator of NMDA neurotransmission, but does not address its passage across the blood-brain barrier. Searches for blood-brain barrier transport and SLC6A14 found no passage in our copy supporting the claimed transport mechanism. (LLM, conf=0.76)
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- Authors
- Wolosker, H., Blackshaw, S., & Snyder, S. H.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-11-09
- Volume
- 96
- Issue
- 23
- Pages
- 13409-13414
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC23961
- OpenAlex
- W2048181000
- Cited by
- 811
- References
- 1
- Citations by year
- 2026: 22 · 2025: 19 · 2024: 25 · 2023: 30 · 2022: 22 · 2021: 36 · 2020: 29 · 2019: 23 · 2018: 28 · 2017: 32 · 2016: 34 · 2015: 29 · 2014: 35 · 2013: 26 · 2012: 34
- FWCI
- 12.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH018501, R37MH018501, MH-18501)
- National Institute on Drug Abuse (DA 00074, K05DA000074)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- serine racemase, D-serine, L-serine, NMDA receptor, glycine site, glutamatergic neurotransmission, glial cells, pyridoxal phosphate-dependent enzymes, D-amino acid metabolism, rat brain, enzyme cloning, neuron-glia interactions
- MeSH terms
- Serine Racemase, Amino Acid Sequence, Animals, Astrocytes, Base Sequence, Cell Line, Humans, Immunohistochemistry, Molecular Sequence Data, Serine, N-Methylaspartate, Sequence Homology, Amino Acid, DNA Primers, Racemases and Epimerases, Rats
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