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

ABSTRACT: In the present 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 (DSD). 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-β-EHAsn on mammalian serine racemase, responsible for producing d-serine, a co-agonist of the N-methyl-d-aspartate (NMDA) receptor involved in glutamatergic neurotransmission.

SUBMITTER: Ito T

PROVIDER: S-EPMC8071972 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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

Ito Tomokazu T Tono Mayuka M Kitaura Yasuyuki Y Hemmi Hisashi H Yoshimura Tohru T

Bioscience reports 20210401 4

In the present 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 (DSD). 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 an ...[more]

PMID: 33821987

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