Abbreviations: PSAT, phosphoserine aminotransferase; PSP, phosphoserine phosphatase; SR, serine racemase
D-serine is produced from L-serine by the enzyme serine racemase
which can be a cause of the decreased serum levels of L-serine as was observed in our study.
D-serine is synthetized by isomerization of L-serine, in a reaction catalyzed by the enzyme serine racemase [24, 25], which, in addition to synthesize D-serine, also catalyzes the [alpha],[beta]-elimination of water from L-serine or D-serine to produce pyruvate and ammonia  (Figure 1).
However, this hypothesis does not consider alternative sources of D-serine like microglia, in which both serine racemase and D-serine are also found.
In the hippocampus, D-serine and serine racemase are predominantly observed in the neuron-rich pyramidal cell- and in the granule cell-layers .
Large genome wide association study of schizophrenia implicated numerous genes involved in glutamatergic transmission, such as genes encoding the GluN2A subunits and serine racemase
Moreover, based on the fact that L-Cys inhibits the activity of serine racemase (Cook et al., 2002), which converts L-Ser to D-Ser and was purified from the mammalian brain (Wolosker et al., 1999; Konno, 2003), it is likely that the sedative and hypnotic effects of L-Cys are partly due to inhibition of the synthesis of D-Ser, which might trigger excitatory responses mediated by NMDA receptor.
Direct calcium binding results in activation of brain serine racemase. J.
Purified serine racemase
has a molecular weight of 37 kDa and requires pyridoxal 5-phosphate for its activity.
EphrinB3 enhances D-serine release by regulating serine racemase
(SR), an enzyme responsible for the conversion of L-serine to D-serine, and an SR-interacting protein, protein linase C (PKC[alpha]).
The activity of serine racemase was inversely regulated by D-serine and NO (25).
This finding also supports the involvement of D-serine in NMDA receptor activation, because D-serine is synthesized from L-serine by serine racemase and glycine has been known to be the precursor of L-serine (2, 3).