Novel tetrahydrofolate-dependent d-serine dehydratase activity of serine hydroxymethyltransferases.

d-Serine plays vital physiological roles in the functional regulation of the mammalian brain, where it is produced from l-serine by serine racemase and degraded by d-amino acid oxidase. In the present study, we identified a new d-serine metabolizing activity of serine hydroxymethyltransferase (SHMT) in bacteria as well as mammals. SHMT is known to catalyze the conversion of l-serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate, respectively.

YgeA is involved in L- and D-homoserine metabolism in Escherichia coli.

Noncanonical D-amino acids are involved in peptidoglycan and biofilm metabolism in bacteria. Previously, we identified amino acid racemases with broad substrate specificity, including YgeA from Escherichia coli, which strongly prefers homoserine as a substrate. In this study, we investigated the functions of this enzyme in vivo.

Characterization of human cystathionine γ-lyase enzyme activities toward d-amino acids.

Various d-amino acids play important physiological roles in mammals, but the pathways of their production remain unknown except for d-serine, which is generated by serine racemase. Previously, we found that Escherichia coli cystathionine β-lyase possesses amino acid racemase activity in addition to β-lyase activity. In the present work, we evaluated the enzymatic activities of human cystathionine γ-lyase, which shares a relatively high amino acid sequence identity with cystathionine β-lyase.

Acetylornithine aminotransferase TM1785 performs multiple functions in the hyperthermophile Thermotoga maritima.

The hyperthermophilic bacterium Thermotoga maritima peptidoglycan contains unusual d-lysine alongside typical d-alanine and d-glutamate. We previously identified lysine racemase and threonine dehydratase, but knowledge of d-amino acid metabolism remains limited. Herein, we identified and characterized T.

Glyoxylate reductase/hydroxypyruvate reductase regulates the free d-aspartate level in mammalian cells.

Multiple d-amino acids are present in mammalian cells, and these compounds have distinctive physiological functions. Among the free d-amino acids identified in mammals, d-aspartate plays critical roles in the neuroendocrine and endocrine systems, as well as in the central nervous system. Mammalian cells have the molecular apparatus necessary to take up, degrade, synthesize, and release d-aspartate.

Identification and biochemical characterization of threonine dehydratase from the hyperthermophile Thermotoga maritima.

The peptidoglycan of the hyperthermophile Thermotoga maritima contains an unusual component, D-lysine (D-Lys), in addition to the typical D-alanine (D-Ala) and D-glutamate (D-Glu). In a previous study, we identified a Lys racemase that is presumably associated with D-Lys biosynthesis. However, our understanding of D-amino acid metabolism in T.

Identification of an l-serine/l-threonine dehydratase with glutamate racemase activity in mammals.

Recent investigations have shown that multiple d-amino acids are present in mammals and these compounds have distinctive physiological functions. Free d-glutamate is present in various mammalian tissues and cells and in particular, it is presumably correlated with cardiac function, and much interest is growing in its unique metabolic pathways. Recently, we first identified d-glutamate cyclase as its degradative enzyme in mammals, whereas its biosynthetic pathway in mammals is unclear.

d-Serine and d-Alanine Regulate Adaptive Foraging Behavior in via the NMDA Receptor.

d-Serine (d-Ser) is a coagonist for NMDA-type glutamate receptors and is thus important for higher brain function. d-Ser is synthesized by serine racemase and degraded by d-amino acid oxidase. However, the significance of these enzymes and the relevant functions of d-amino acids remain unclear.

Dysfunctional d-aspartate metabolism in BTBR mouse model of idiopathic autism.

Background: Autism spectrum disorders (ASD) comprise a heterogeneous group of neurodevelopmental conditions characterized by impairment in social interaction, deviance in communication, and repetitive behaviors. Dysfunctional ionotropic NMDA and AMPA receptors, and metabotropic glutamate receptor 5 activity at excitatory synapses has been recently linked to multiple forms of ASD. Despite emerging evidence showing that d-aspartate and d-serine are important neuromodulators of glutamatergic transmission, no systematic investigation on the occurrence of these D-amino acids in preclinical ASD models has been carried out.

A colorimetric assay method for measuring d-glutamate cyclase activity.

In mammals, metabolism of free d-glutamate is regulated by d-glutamate cyclase (DGLUCY), which reversibly converts d-glutamate to 5-oxo-d-proline and HO. Metabolism of these d-amino acids by DGLUCY is thought to regulate cardiac function. In this study, we established a simple, accurate, and sensitive colorimetric assay method for measuring DGLUCY activity.

Biochemical characterization of d-aspartate oxidase from Caenorhabditis elegans: its potential use in the determination of free d-glutamate in biological samples.

d-Aspartate oxidase (DDO) is a flavin adenine dinucleotide (FAD)-containing flavoprotein that stereospecifically acts on acidic d-amino acids (i.e., free d-aspartate and d-glutamate).

Involvement of penicillin-binding proteins in the metabolism of a bacterial peptidoglycan containing a non-canonical D-amino acid.

Bacteria produce various D-amino acids, including non-canonical D-amino acids, to adapt to environmental changes and overcome a variety of threats. These D-amino acids are largely utilized as components of peptidoglycan, and they promote peptidoglycan remodeling and biofilm disassembly. The biosynthesis, maturation, and recycling of peptidoglycan are catalyzed by penicillin-binding proteins (PBPs).

Elucidation of the d-lysine biosynthetic pathway in the hyperthermophile Thermotoga maritima.

Various d-amino acids are involved in peptidoglycan and biofilm metabolism in bacteria, suggesting that these compounds are necessary for successful adaptation to environmental changes. In addition to the conventional d-alanine (d-Ala) and d-glutamate, the peptidoglycan of the hyperthermophilic bacterium Thermotoga maritima contains both l-lysine (l-Lys) and d-Lys, but not meso-diaminopimelate (meso-Dpm). d-Lys is an uncommon component of peptidoglycan, and its biosynthetic pathway remains unclear.

Secreted d-aspartate oxidase functions in C. elegans reproduction and development.

d-Aspartate oxidase (DDO) is a degradative enzyme that acts stereospecifically on free acidic D-amino acids such as d-aspartate and d-glutamate. d-Aspartate plays an important role in regulating neurotransmission, developmental processes, hormone secretion, and reproductive functions in mammals. In contrast, the physiological role of d-glutamate in mammals remains unclear.

Structural and enzymatic properties of mammalian d-glutamate cyclase.

d-Glutamate cyclase (DGLUCY) is a unique enzyme that reversibly converts free d-glutamate to 5-oxo-d-proline and HO. Mammalian DGLUCY is highly expressed in the mitochondrial matrix in the heart, and its downregulation disrupts d-glutamate and/or 5-oxo-d-proline levels, contributing to the onset and/or exacerbation of heart failure. However, detailed characterisation of DGLUCY has not yet been performed.

Cystathionine β-lyase is involved in d-amino acid metabolism.

Non-canonical d-amino acids play important roles in bacteria including control of peptidoglycan metabolism and biofilm disassembly. Bacteria appear to produce non-canonical d-amino acids to adapt to various environmental changes, and understanding the biosynthetic pathways is important. We identified novel amino acid racemases possessing the ability to produce non-canonical d-amino acids in and in our previous study, whereas the biosynthetic pathways of these d-amino acids still remain unclear.

Rat d-aspartate oxidase is more similar to the human enzyme than the mouse enzyme.

d-Aspartate oxidase (DDO) is a degradative enzyme that is stereospecific for the acidic amino acid d-aspartate, an endogenous agonist of the N-methyl-d-aspartate (NMDA) receptor. Dysregulation of NMDA receptor-mediated neurotransmission has been implicated in the onset of various neuropsychiatric disorders including schizophrenia, as well as chronic pain. Thus, appropriate regulation of d-aspartate is believed to be important for maintaining proper neural activity in the nervous system.

Identification and characterization of novel broad-spectrum amino acid racemases from Escherichia coli and Bacillus subtilis.

The peptidoglycan layer of the bacterial cell wall typically contains D-alanine (D-Ala) and D-glutamic acid (D-Glu), and also various non-canonical D-amino acids that have been linked to peptidoglycan remodeling, inhibition of biofilm formation, and triggering of biofilm disassembly. Bacteria produce D-amino acids when adapting to environmental changes as a common survival strategy. In our previous study, we detected non-canonical D-amino acids in Escherichia coli grown in minimal medium.

Structure-function relationships in human d-aspartate oxidase: characterisation of variants corresponding to known single nucleotide polymorphisms.

d-Aspartate oxidase (DDO) is a degradative enzyme that is stereospecific for the acidic amino acid d-aspartate, an endogenous agonist of the N-methyl-d-aspartate (NMDA) receptor. Dysregulation of NMDA receptor-mediated neurotransmission has been implicated in the onset of various neuropsychiatric disorders including schizophrenia and in chronic pain. Thus, appropriate regulation of the amount of d-aspartate is believed to be important for maintaining proper neural activity in the nervous system.

Detection of diastereomer peptides as the intermediates generating D-amino acids during acid hydrolysis of peptides.

In this study, we investigated whether the amino acid residues within peptides were isomerized (and the peptides converted to diastereomers) during the early stages of acid hydrolysis. We demonstrate that the model dipeptides L-Ala-L-Phe and L-Phe-L-Ala are epimerized to produce the corresponding diastereomers at a very early stage, prior to their acid hydrolytic cleavage to amino acids. Furthermore, the sequence-inverted dipeptides were generated via formation of a diketopiperazine during hydrolytic incubation, and these dipeptides were also epimerized.

Quantitative In Silico Analysis of Retention of Nitrobenzofurazan-Amino Acids in Reversed-Phase Ion-Pair Liquid Chromatography.

The retention mechanisms of nitrobenzofurazan (NBD)-amino acids in reversed-phase ion-pair liquid chromatography were quantitatively analyzed in silico The most contributed interaction for the retention is the Lewis acid-base interaction between an aromatic ring of NBD-amino acids and hydroxyl-group hydrogen of tetra-butyl-ammonium hydroxide coated on the hydrophobic phase. Solvent effects significantly improved the relation between the calculated molecular interaction (MI) energy values using a molecular mechanics program and log k values measured in chromatography. The correlation coefficient between the calculated MI energy values and the log k values was >0.

Multi-regression analysis revealed a relationship between l-serine and methionine, a component of one-carbon metabolism, in the normal control but not in the schizophrenia.

Background: Alterations in one-carbon metabolism (OCM) have been observed in patients with schizophrenia (SZ), but a comprehensive study of OCM has not yet been conducted. A carbon atom is transferred from l-serine to methionine during OCM, but the relationship between l-serine and methionine in SZ is not yet known. We investigated the relationship between l-serine and methionine to obtain a comprehensive understanding of OCM in SZ.

Characterization of a homologue of mammalian serine racemase from Caenorhabditis elegans: the enzyme is not critical for the metabolism of serine in vivo.

Free d-serine (d-Ser) plays a crucial role in regulating brain function in mammals. In various organisms, including mammals, d-Ser is biosynthesized by Ser racemase, a synthetic enzyme that produces d-Ser from l-Ser. Ser racemase also exhibits dehydratase activity toward several hydroxyamino acids.

Structural and functional characterization of aspartate racemase from the acidothermophilic archaeon Picrophilus torridus.

Functional and structural characterizations of pyridoxal 5'-phosphate-independent aspartate racemase of the acidothermophilic archaeon Picrophilus torridus were performed. Picrophilus aspartate racemase exhibited high substrate specificity to aspartic acid. The optimal reaction temperature was 60 °C, which is almost the same as the optimal growth temperature.