Serine racemase (SRR) is a pyridoxal phosphate-dependent enzyme that catalyzes the conversion of L-serine to D-serine 1. D-serine functions as a critical coagonist with glutamate at NMDA receptors in the forebrain, where it binds to the NR1 channel subunit to enable receptor activation 1. The enzyme operates through a reversible racemization mechanism and also possesses dehydratase activity toward both L-serine and D-serine substrates. SRR is predominantly localized to neuronal cell bodies and the cytosol, where it forms homodimers and interacts with PDZ domain-containing proteins. Genetically, SRR represents one of approximately two dozen schizophrenia risk genes affecting NMDA receptor function 1. In animal models, srr gene inactivation results in ~90% loss of endogenous D-serine and ~70% reduction in NMDA receptor function, producing schizophrenia-like phenotypes including cortical atrophy, synaptic spine loss, and cognitive impairments 1. Additionally, intronic SRR variants modulate expression of the neighboring SMG6 gene; the protective GG genotype at rs4523957 decreases SMG6 promoter activity and reduces temporal lobe epilepsy susceptibility and seizure severity 2. These findings implicate SRR-dependent D-serine synthesis in glutamatergic neurotransmission and reveal its relevance to neuropsychiatric and neurological diseases involving NMDA receptor hypofunction.
No related genes found for this gene.
No tissue expression data available for this gene.