Commentary on Urinary L-erythro-beta-hydroxyasparagine: a novel serine racemase inhibitor and substrate of the Zn2+-dependent D-serine dehydratase

The analysis of the urine contents can be informative of physiological homoeostasis, and it has been speculated that the levels of urinary D-serine (D-ser) could inform about neurological and renal disorders. By analysing the levels of urinary D-ser using a D-ser dehydratase (DSD) enzyme, Ito et al. (Biosci. Rep.(2021) 41, BSR20210260) have described abundant levels of L-erythro-beta-hydroxyasparagine (L-beta-EHAsn), a non-proteogenic amino acid which is also a newly described substrate for DSD. The data presented support the endogenous production L-beta-EHAsn, with its concentration significantly correlating with the concentration of creatinine in urine. Taken together, these results could raise speculations that L-beta-EHAsn might have unexplored important biological roles. It has been demonstrated that L-beta-EHAsn also inhibits serine racemase with K-i values (40 mu M) similar to its concentration in urine (50 mu M). Given that serine racemase is the enzyme involved in the synthesis of D-ser, and L-beta-EHAsn is also a substrate for DSD, further investigations could verify if this amino acid would be involved in the metabolic regulation of pathways involving D-ser.