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

Fabio K. Tamaki

doi:10.1042/BSR20211524C

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

Fabio K. Tamaki (Lead / Corresponding author)

Drug Discovery Unit

Research output: Contribution to journal › Comment/debate › peer-review

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Abstract

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-β-hydroxyasparagine (l-β-EHAsn), a non-proteogenic amino acid which is also a newly described substrate for DSD. The data presented support the endogenous production l-β-EHAsn, with its concentration significantly correlating with the concentration of creatinine in urine. Taken together, these results could raise speculations that l-β-EHAsn might have unexplored important biological roles. It has been demonstrated that l-β-EHAsn also inhibits serine racemase with Ki values (40 μM) similar to its concentration in urine (50 μM). Given that serine racemase is the enzyme involved in the synthesis of d-ser, and l-β-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.

Original language	English
Article number	BSR20211524
Pages (from-to)	1-3
Number of pages	3
Journal	Bioscience Reports
Volume	41
Issue number	12
Early online date	22 Nov 2021
DOIs	https://doi.org/10.1042/BSR20211524C
Publication status	Published - 7 Dec 2021

Keywords

d-serine
amino acids
serine racemase

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10.1042/BSR20211524CLicence: CC BY

Final Published VersionFinal published version, 221 KBLicence: CC BY

Cite this

@article{d7edfc76818e4e2cbb5b04e75c57f80f,

title = "Commentary on Urinary L-erythro-β-hydroxyasparagine: a novel serine racemase inhibitor and substrate of the Zn2+-dependent D-serine dehydratase",

abstract = "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-β-hydroxyasparagine (l-β-EHAsn), a non-proteogenic amino acid which is also a newly described substrate for DSD. The data presented support the endogenous production l-β-EHAsn, with its concentration significantly correlating with the concentration of creatinine in urine. Taken together, these results could raise speculations that l-β-EHAsn might have unexplored important biological roles. It has been demonstrated that l-β-EHAsn also inhibits serine racemase with Ki values (40 μM) similar to its concentration in urine (50 μM). Given that serine racemase is the enzyme involved in the synthesis of d-ser, and l-β-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.",

keywords = "d-serine, amino acids, serine racemase",

author = "Tamaki, \{Fabio K.\}",

note = "This work was supported by the {\textquoteleft}Bill \& Melinda Gates Foundation{\textquoteright} – {\textquoteleft}Lead Optimization Research Identifying Novel Agents for Diseases of the Developing World (LEOPARD){\textquoteright} [grant number OPP1191579]; and the {\textquoteleft}Wellcome Centre for Anti-Infectives Research{\textquoteright} (WCAIR – University of Dundee).",

year = "2021",

month = dec,

day = "7",

doi = "10.1042/BSR20211524C",

language = "English",

volume = "41",

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journal = "Bioscience Reports",

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publisher = "Portland Press",

number = "12",

}

TY - JOUR

T1 - Commentary on Urinary L-erythro-β-hydroxyasparagine

T2 - a novel serine racemase inhibitor and substrate of the Zn2+-dependent D-serine dehydratase

AU - Tamaki, Fabio K.

N1 - This work was supported by the ‘Bill & Melinda Gates Foundation’ – ‘Lead Optimization Research Identifying Novel Agents for Diseases of the Developing World (LEOPARD)’ [grant number OPP1191579]; and the ‘Wellcome Centre for Anti-Infectives Research’ (WCAIR – University of Dundee).

PY - 2021/12/7

Y1 - 2021/12/7

N2 - 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-β-hydroxyasparagine (l-β-EHAsn), a non-proteogenic amino acid which is also a newly described substrate for DSD. The data presented support the endogenous production l-β-EHAsn, with its concentration significantly correlating with the concentration of creatinine in urine. Taken together, these results could raise speculations that l-β-EHAsn might have unexplored important biological roles. It has been demonstrated that l-β-EHAsn also inhibits serine racemase with Ki values (40 μM) similar to its concentration in urine (50 μM). Given that serine racemase is the enzyme involved in the synthesis of d-ser, and l-β-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.

AB - 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-β-hydroxyasparagine (l-β-EHAsn), a non-proteogenic amino acid which is also a newly described substrate for DSD. The data presented support the endogenous production l-β-EHAsn, with its concentration significantly correlating with the concentration of creatinine in urine. Taken together, these results could raise speculations that l-β-EHAsn might have unexplored important biological roles. It has been demonstrated that l-β-EHAsn also inhibits serine racemase with Ki values (40 μM) similar to its concentration in urine (50 μM). Given that serine racemase is the enzyme involved in the synthesis of d-ser, and l-β-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.

KW - d-serine

KW - amino acids

KW - serine racemase

U2 - 10.1042/BSR20211524C

DO - 10.1042/BSR20211524C

M3 - Comment/debate

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SN - 0144-8463

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