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, I
n glial cul tures of rat cerebral cortex, D-serine is enriched in type II a
strocytes and is released upon stimulation with agonists of non-N-methyl-D-
aspartate glutamate receptors, The high levels of D-serine in discrete area
s of rat brain imply the existence of a biosynthetic pathway, We have purif
ied 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 3
7 kDa and requires pyridoxal 5'-phosphate for its activity. The enzyme is h
ighly selective toward L-serine, failing to racemize any other amino acid t
ested. Properties such as pH optimum, K-m values, and the requirement for p
yridoxal phosphate resemble those of bacterial racemases, suggesting that t
he biosynthetic pathway for D-amino acids is conserved from bacteria to mam
malian brain.