Urinary l-erythro-β-hydroxyasparagine—a novel serine racemase inhibitor and substrate of the Zn2+-dependent d-serine dehydratase

Abstract

In this study, we identified L-erythro-β-hydroxyasparagine (L-β-EHAsn) found abundantly in human urine, as a novel substrate of Zn2+-dependent D-serine dehydratase. L-β-EHAsn is an atypical amino acid present in large amounts in urine but rarely detected in serum or most organs/tissues examined. Quantitative analyses of urinary L-β-EHAsn in young healthy volunteers revealed significant correlation between urinary L-β-EHAsn concentration and creatinine level. Further, for in-depth analyses of L-β-EHAsn, we developed a simple three-step synthetic method using trans-epoxysuccinic acid as the starting substance. In addition, our research revealed a strong inhibitory effect of l-b-EHAsn on mammalian serine racemase, responsible for producing D-serine, a co-agonist of the N-methyl-D-aspartate receptor involved in glutamatergic neurotransmission.

Commentary on Urinary l-erythro-β-hydroxyasparagine: a novel serine racemase inhibitor and substrate of the Zn2+-dependent d-serine dehydratase

“…These works also resulted in the finding of a new unknown substrate for Dsd1p in urine. In this paper [5], Ito et al initially found that the new Dsd1p substrate is the amino acid β-hydroxyl asparagine. For this, they have analysed the amino acid contents in urine using a cascade of coupled reactions employing enzymes that recognise d-amino acids (Dsd1p and DAAT).…”

“…These works also resulted in the finding of a new unknown substrate for Dsd1p in urine. In this paper [ 5 ], Ito et al . initially found that the new Dsd1p substrate is the amino acid β-hydroxyl asparagine.…”