Biochemical characterization of serine racemases from major mammalian lineages.
TL;DR
Findings show conservation of SR function across the mammalian lineages examined, with species-dependent differences in catalytic properties and expression.
Abstract
Serine racemase (SR) catalyzes the interconversion of l-serine and d-serine and can also catalyze β-elimination of serine to pyruvate and ammonia. In mammals, however, the presence and enzymatic function of SR have been reported mainly in mouse, rat, and human. It is therefore unclear whether functional SR is broadly conserved across mammals or whether its enzymatic properties differ among lineages. To address this question, we produced and purified eleven SRs from representative eutherians, marsupials, and a monotreme and compared their catalytic properties. All enzymes examined showed both racemization and β-elimination activities. Together with the phylogenetic relationships, these activities suggest that functional SR was present before the monotreme-therian divergence and retained in the lineages examined. Specific activities and kinetic parameters nevertheless differed among species. Residues involved in cofactor and substrate binding were broadly conserved, whereas variation at the substrate-recognition region around positions 150-152 may contribute to the observed kinetic differences. Analysis of public transcriptome data further suggested species differences in tissue expression patterns. Together, these findings show conservation of SR function across the mammalian lineages examined, with species-dependent differences in catalytic properties and expression.