Purification of serine racemase: Biosynthesis of the neuromodulator D-serine

Herman Wolosker, Kevin N. Sheth, Masaaki Takahashi, Jean Pierre Mothet, Roscoe O. Brady, Christopher D. Ferris, Solomon H. Snyder

Research output: Contribution to journalArticle

Abstract

High levels of D-serine occur in mammalian brain, where it appears to be an endogenous ligand of the glycine site of N-methyl-D-aspartate receptors. In glial cultures of rat cerebral cortex, D-serine is enriched in type-II astrocytes and is released upon stimulation with agonists of non-N-methyl-D-aspartate glutamate receptors. The high levels of D-serine in discrete areas of rat brain imply the existence of a biosynthetic pathway. We have purified from rat brain a soluble enzyme that catalyzes the direct racemization of L-serine to D-serine. Purified serine racemase has a molecular mass of 37 kDa and requires pyridoxal 5′-phosphate for its activity. The enzyme is highly selective toward L-serine, failing to racemize any other amino acid tested. 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.

Original languageEnglish (US)
Pages (from-to)721-725
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number2
DOIs
StatePublished - Jan 19 1999

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