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

2021 ◽  
Vol 41 (12) ◽  
Author(s):  
Fabio K. Tamaki
Keyword(s):  
Amino Acid ◽  
Metabolic Regulation ◽  
Serine Racemase ◽  
Renal Disorders ◽  
Endogenous Production ◽  
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.

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

2021 ◽  
Author(s):  
Fabio Kendi Tamaki
Keyword(s):  
Amino Acid ◽  
Metabolic Regulation ◽  
Serine Racemase ◽  
Renal Disorders ◽  
Endogenous Production ◽  
Serine Dehydratase ◽  
Physiological Homeostasis

The analysis of the urine contents can be informative of physiological homeostasis, 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. have described abundant levels of L-β-EHAsn, a non-proteogenic amino acid which is also a newly described substrate for DSD. The data presented supports 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.

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

2021 ◽  
Vol 41 (4) ◽  
Author(s):  
Tomokazu Ito ◽  
Mayuka Tono ◽  
Yasuyuki Kitaura ◽  
Hisashi Hemmi ◽  
Tohru Yoshimura
Keyword(s):  
Amino Acid ◽  
Nmda Receptor ◽  
Human Urine ◽  
Inhibitory Effect ◽  
Serine Racemase ◽  
Synthetic Method ◽  
Glutamatergic Neurotransmission ◽  
Serine Dehydratase ◽  
Strong Inhibitory Effect ◽  
Quantitative Analyses

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.

Dietary protein paradox: decrease of amino acid availability induced by high-protein diets

1993 ◽  
Vol 264 (6) ◽  
pp. G1057-G1065 ◽  
Author(s):  
C. Moundras ◽  
C. Remesy ◽  
C. Demigne
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Dietary Protein ◽  
High Protein ◽  
Glutamine Metabolism ◽  
Metabolic Adaptation ◽  
Casein Diet ◽  
Serine Dehydratase ◽  
High Protein Diets ◽  
Protein Diets

The aim of the present study was to evaluate the effect of changes in dietary protein level on overall availability of amino acids for tissues. For this purpose, rats were adapted to diets containing various concentrations of casein (7.5, 15, 30, and 60%) and were sampled either during the postprandial or postabsorptive period. In rats fed the protein-deficient diet, glucogenic amino acids (except threonine) tended to accumulate in plasma, liver, and muscles. In rats fed high-protein diets, the hepatic balance of glucogenic amino acids was markedly enhanced and their liver concentrations were consistently depressed. This response was the result of a marked induction of amino acid catabolism (a 45-fold increase of liver threonine-serine dehydratase activity was observed with the 60% casein diet). The muscle concentrations of threonine, serine, and glycine underwent changes parallel to plasma and liver concentrations, and a significant reduction of glutamine was observed. During the postabsorptive period, adaptation to high-protein diets resulted in a sustained catabolism of most glucogenic amino acids, which accentuated the drop in their concentrations (especially threonine) in all the compartments studied. The time course of metabolic adaptation from a 60 to a 15% casein diet has also been investigated. Adaptation of alanine and glutamine metabolism was rapid, whereas that of threonine, serine, and glycine was delayed and required 7-11 days. This was paralleled by a relatively slow decay of liver threonine-serine dehydratase (T-SDH) activity in contrast to the rapid adaptation of pyruvate kinase activity after refeeding a high-carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Factors regulating serine racemase and d-amino acid oxidase expression in the mouse striatum

2021 ◽  
Vol 1751 ◽  
pp. 147202
Author(s):  
Shunsuke Takagi ◽  
Darrick T. Balu ◽  
Joseph T. Coyle
Keyword(s):  
Amino Acid ◽  
Serine Racemase ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Mouse Striatum

scholarly journals Carbohydrate formation from various precursors in neonatal rat liver

1968 ◽  
Vol 110 (4) ◽  
pp. 725-731 ◽  
Author(s):  
R. G. Vernon ◽  
Susan W. Eaton ◽  
D G Walker
Keyword(s):  
Amino Acid ◽  
Rat Liver ◽  
Neonatal Period ◽  
Casein Hydrolysate ◽  
Amino Acid Mixture ◽  
Neonatal Rat ◽  
Acid Mixture ◽  
Hepatic Gluconeogenesis ◽  
Threonine Dehydratase ◽  
Serine Dehydratase

1. Measurements of the net synthesis of glucose plus glycogen from various precursors in slices of glycogen-depleted livers from rats at various stages of development indicated an increase in the gluconeogenic capacity after birth with l-lactate, oxaloacetate, a casein hydrolysate, l-serine, l-threonine, l-alanine and glycerol as substrates. 2. The highest rates of incorporation of 14C-labelled precursors into glucose plus glycogen in slices of normal livers of rats of various ages were observed in such tissue preparations from neonatal animals for an amino acid mixture, l-alanine, l-serine and l-threonine. 3. The activities of rat hepatic l-serine dehydratase and l-threonine dehydratase increase rapidly after birth and show maxima about 20 days later. 4. The results provide further evidence of the increased capacity for hepatic gluconeogenesis in the neonatal period and suggest various sites of regulation of the process.

scholarly journals d-Amino acid oxidase and serine racemase in human brain: normal distribution and altered expression in schizophrenia

2007 ◽  
Vol 26 (6) ◽  
pp. 1657-1669 ◽  
Author(s):  
Louise Verrall ◽  
Mary Walker ◽  
Nancy Rawlings ◽  
Isabel Benzel ◽  
James N. C. Kew ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Brain ◽  
Normal Distribution ◽  
Serine Racemase ◽  
Acid Oxidase ◽  
Amino Acid Oxidase ◽  
Altered Expression

scholarly journals Biochemical and Genetic Characterization of the vanC-2 Vancomycin Resistance Gene Cluster of Enterococcus casseliflavus ATCC 25788

2002 ◽  
Vol 46 (10) ◽  
pp. 3125-3132 ◽  
Author(s):  
Ireena Dutta ◽  
Peter E. Reynolds
Keyword(s):  
Amino Acid ◽  
Gene Cluster ◽  
Response Regulator ◽  
Extended Period ◽  
Amino Acid Identity ◽  
Serine Racemase ◽  
Gene Encoding ◽  
Acid Identity ◽  
Induction Process ◽  
Enterococcus Casseliflavus

ABSTRACT The vanC-2 cluster of Enterococcus casseliflavus ATCC 25788 consisted of five genes (vanC-2, vanXYC-2 , vanTC-2 , vanRC-2 , and vanSC-2 ) and shared the same organization as the vanC cluster of E. gallinarum BM4174. The proteins encoded by these genes displayed a high degree of amino acid identity to the proteins encoded within the vanC gene cluster. The putative d,d-dipeptidase-d,d-carboxypeptidase, VanXYC-2, exhibited 81% amino acid identity to VanXYC, and VanTC-2 displayed 65% amino acid identity to the serine racemase, VanT. VanRC-2 and VanSC-2 displayed high degrees of identity to VanRC and VanSC, respectively, and contained the conserved residues identified as important to their function as a response regulator and histidine kinase, respectively. Resistance to vancomycin was expressed inducibly in E. casseliflavus ATCC 25788 and required an extended period of induction. Analysis of peptidoglycan precursors revealed that UDP-N-acetylmuramyl-l-Ala-δ-d-Glu-l-Lys-d-Ala-d-Ser could not be detected until several hours after the addition of vancomycin, and its appearance coincided with the resumption of growth. The introduction of additional copies of the vanTC-2 gene, encoding a putative serine racemase, and the presence of supplementary d-serine in the growth medium both significantly reduced the period before growth resumed after addition of vancomycin. This suggested that the availability of d-serine plays an important role in the induction process.

Ketamine enhances the expression of serine racemase and d-amino acid oxidase mRNAs in rat brain

2006 ◽  
Vol 540 (1-3) ◽  
pp. 82-86 ◽  
Author(s):  
Kazuhide Takeyama ◽  
Masanobu Yoshikawa ◽  
Tetsuo Oka ◽  
Mitsuru Kawaguchi ◽  
Toshiyasu Suzuki ◽  
...  
Keyword(s):  
Amino Acid ◽  
Rat Brain ◽  
Serine Racemase ◽  
Acid Oxidase ◽  
Amino Acid Oxidase

scholarly journals Sequence analysis and structure prediction of ABHD16A and the roles of the ABHD family members in human disease

Open Biology ◽  
2018 ◽  
Vol 8 (5) ◽  
pp. 180017 ◽  
Author(s):  
Jun Xu ◽  
Weizhen Gu ◽  
Kai Ji ◽  
Zhao Xu ◽  
Haihua Zhu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Structure Prediction ◽  
Active Sites ◽  
Metabolic Regulation ◽  
Acid Sites ◽  
Amino Acid Sequences ◽  
The Body ◽  
Gene Location ◽  
Future Research ◽  
Animal Cells

Abhydrolase domain containing 16A (ABHD16A) is a member of the α/β hydrolase domain-containing (ABHD) protein family and is expressed in a variety of animal cells. Studies have shown that ABHD16A has acylglycerol lipase and phosphatidylserine lipase activities. Its gene location in the main histocompatibility complex (MHC) III gene cluster suggests that this protein may participate in the immunomodulation of the body. The results of studies investigating nearly 20 species of ABHDs reveal that the ABHD proteins are key factors in metabolic regulation and disease occurrence and development. In this paper, we summarize the related progress regarding the function of ABHD16A and other ABHD proteins. A prediction of the active sites and structural domains of ABHD16A and an analysis of the amino acid sites are included. Moreover, we analysed the amino acid sequences of the ABHD16A molecules in different species and provide an overview of the related functions and diseases associated with these proteins. The functions and diseases related to ABHD are systematically summarized and highlighted. Future research directions for studies investigating the functions and mechanisms of these proteins are also suggested. Further studies investigating the function of ABHD proteins may further confirm their positions as important determinants of lipid metabolism and related diseases.

Purification and partial amino acid sequence of a glutamyl-tRNA synthetase from Rhizobium meliloti

1989 ◽  
Vol 67 (10) ◽  
pp. 674-679 ◽  
Author(s):  
Serge Laberge ◽  
Manon Belair ◽  
Alain Verreault ◽  
Alexander W. Bell ◽  
Lucien M. Bordeleau ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Metabolic Regulation ◽  
Rhizobium Meliloti ◽  
Reversed Phase ◽  
Trna Synthetase ◽  
Partial Amino Acid Sequence ◽  
Amino Terminal ◽  
Internal Peptide ◽  
Single Polypeptide

A glutamyl-tRNA synthetase has been purified to homogeneity from Rhizobium meliloti, using reversed-phase chromatography as the last step. Amino acid sequencing of the amino-terminal region of the enzyme indicates that it contains a single polypeptide, whose molecular weight is about 54 000, as judged by SDS–gel electrophoresis. The primary structures of the amino-terminus region and of an internal peptide obtained by cleavage of the enzyme with CNBr have similarities of 58 and 48% with regions of the glutamyl-tRNA sythetase of Escherichia coli; these are thought to be involved in the binding of ATP and tRNA, respectively. The small amount of glutamyl-tRNA synthetase present in R. meliloti is consistent with the metabolic regulation of the biosynthesis of many aminoacyl-tRNA synthetases.Key words: glutamyl-tRNA synthetase, Rhizobium meliloti, purification, reverse-phase chromatography, amino acid sequence.

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