D-serine dehydratase (DSD)

D-serine dehydratase (DSD) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the deamination of D-serine to produce pyruvate and ammonia [1, 16]. While humans primarily catabolize D-serine using D-amino acid oxidase (DAAO), DSD is found in various bacteria and lower eukaryotes like yeast, where it serves as a crucial detoxification mechanism against high D-serine concentrations [16]. In pathogenic bacteria such as uropathogenic Escherichia coli (UPEC), DSD is essential for fitness and survival within the host's urinary tract [7, 16]. From a therapeutic perspective, DSD is being explored as a protein-based drug (biologic) to treat neurological disorders characterized by N-methyl-D-aspartate (NMDA) receptor overactivation [12]. For example, PEGylated yeast D-serine dehydratase (PEG-Dsd1p) has been investigated for its ability to lower brain D-serine levels and reduce excitotoxic damage [12]. Because D-serine acts as a critical co-agonist at the NMDA receptor, DSD activity or its use as a therapeutic agent is relevant to psychiatric conditions like schizophrenia and neurodegenerative diseases like Alzheimer's, where D-serine levels are frequently dysregulated [18, 19].

Other names

D-serine ammonia-lyaseD-serine deaminaseD-serine lyaseD-serine hydrolaseD-hydroxyaminoacid dehydrataseDsdADsd1p

Dehydrative deamination of D-serine via a Schiff base intermediate with pyridoxal 5'-phosphate, producing an alpha-aminoacrylate that hydrolyzes to pyruvate and ammonia [1, 14, 16, 22]