Glycine Synthesis Research Articles

Photocatalytic Synthesis of Glycine from Methanol and Nitrate

AbstractPhotocatalytic utilization of methanol and nitrate as carbon and nitrogen sources for the direct synthesis of amino acids could provide a sustainable way for the valorization of green “liquid sunlight” and nitrate waste. In this study, we develop an efficient photochemical method to synthesize glycine directly from methanol and nitrate, which cascades the C−C coupling to form glycol, nitrate reduction to NH3, and finally C−N coupling to generate glycine. Interestingly, the involved photocatalytic tandem reactions show a synergistic effect, in which the presence of nitrate is the dominant factor to enable the overall reaction and reach high synthetic efficiency. Ba2+−TiO2 nanoparticles are confirmed as a feasible and efficient catalyst system for the photosynthesis of glycine with a remarkable glycine photosynthesis rate of 870 μmol gcat−1 h−1 under optimal conditions. This work establishes a novel catalytic system for amino acid synthesis from methanol and nitrate under mild conditions. These results also allow us to further suppose the formation pathways of amino acids on the primitive earth, as an extension to proposals based on the Miller‐Urey experiments.

Glycine synthesis from nitrate and glyoxylate mediated by ferroan brucite: An integrated pathway for prebiotic amine synthesis

Amino acids are present in all known life, so identifying the environmental conditions under which they can be synthesized constrains where life on Earth might have formed and where life might be found on other planetary bodies. All known abiotic amino acid syntheses require ammonia, which is only produced in reducing and neutral atmospheres. Here, we demonstrate that the Fe-bearing hydroxide mineral ferroan brucite [Fe0.33,Mg0.67(OH)2] can mediate the reaction of nitrate and glyoxylate to form glycine, the simplest amino acid used in life. Up to 97% of this glycine was detected only after acid digestion of the mineral, demonstrating that it had been strongly partitioned to the mineral. The dicarboxylic amino acid 3-hydroxy aspartate was also detected, which suggests that reactants underwent a mechanism that simultaneously produced mono- and dicarboxylic amino acids. Nitrate can be produced in both neutral and oxidizing atmospheres, so reductive amination of nitrate and glyoxylate on a ferroan brucite surface expands origins of life scenarios. First, it expands the environmental conditions in which life's precursors could form to include oxidizing atmospheres. Second, it demonstrates the ability of ferroan brucite, an abundant, secondary mineral in serpentinizing systems where olivine is partly hydrated, to mediate reductive amination. Finally, the results demonstrate the need to consider mineral-bound products when analyzing samples for abiotic amino acid synthesis.

Oriented Synthesis of Glycine from CO2, N2, and H2O via a Cascade Process

AbstractAir contains carbon, hydrogen, oxygen, and nitrogen elements that are essential for the constitution of amino acids. Converting the air into amino acids, powered with renewable electricity, provides a green and sustainable alternative to petrochemical‐based methods that produce waste and pollution. Here, taking glycine as an example, we demonstrated the complete production chain for electrorefining amino acids directly from CO2, N2, and H2O. Such a prospective Scheme was composed of three modules, linked by a spontaneous C−N bond formation process. The high‐purity bridging intermediates, separated from the stepwise synthesis, boosted both the carbon selectivity from CO2 to glycine of 91.7 % and nitrogen selectivity from N2 to glycine of 98.7 %. Under the optimum condition, we obtained glycine with a partial current density of 160.8 mA cm−2. The high‐purity solid glycine product was acquired with a separation efficiency of 98.4 %. This work unveils a green and sustainable method for the abiotic creation of amino acids from the air components.

MYC-dependent upregulation of the de novo serine and glycine synthesis pathway is a targetable metabolic vulnerability in group 3 medulloblastoma.

Group 3 medulloblastoma (MBGRP3) represents around 25% of medulloblastomas and is strongly associated with c-MYC (MYC) amplification, which confers significantly worse patient survival. Although elevated MYC expression is a significant molecular feature in MBGRP3, direct targeting of MYC remains elusive, and alternative strategies are needed. The metabolic landscape of MYC-driven MBGRP3 is largely unexplored and may offer novel opportunities for therapies. To study MYC-induced metabolic alterations in MBGRP3, we depleted MYC in isogenic cell-based model systems, followed by 1H high-resolution magic-angle spectroscopy (HRMAS) and stable isotope-resolved metabolomics, to assess changes in intracellular metabolites and pathway dynamics. Steady-state metabolic profiling revealed consistent MYC-dependent alterations in metabolites involved in one-carbon metabolism such as glycine. 13C-glucose tracing further revealed a reduction in glucose-derived serine and glycine (de novo synthesis) following MYC knockdown, which coincided with lower expression and activity of phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in this pathway. Furthermore, MYC-overexpressing MBGRP3 cells were more vulnerable to pharmacological inhibition of PHGDH compared to those with low expression. Using in vivo tumor-bearing genetically engineered and xenograft mouse models, pharmacological inhibition of PHGDH increased survival, implicating the de novo serine/glycine synthesis pathway as a pro-survival mechanism sustaining tumor progression. Critically, in primary human medulloblastomas, increased PHGDH expression correlated strongly with both MYC amplification and poorer clinical outcomes. Our findings support a MYC-induced dependency on the serine/glycine pathway in MBGRP3 that represents a novel therapeutic treatment strategy for this poor prognosis disease group.

Industrial-grade electrocatalytic synthesis of glycine from oxalic acid and nitrate using a porous PbSnBi catalyst

Electrochemical transformation of oxalic acid and nitrate into glycine is an appealing way for valuable chemical synthesis and waste nitrate treatment. Currently, strategies to electrosynthesis of amino acid through catalyst design have been successfully developed, but it is still of huge challenge to realize industrial grade electrocatalytic synthesis of amino acid. Here, we develope an innovative electrochemical method to synthesize glycine from harnessing nitrate (NO3-) and oxalic acid in an aqueous electrolyte with a porous PbSnBi alloy catalyst. By means of construction the multiple catalytic sites and regulation electrode surface microenvironment, this strategy produces glycine with high Faraday efficiencies of 57.2 %, high yield rates of 1.125 mmol h−1 cm−2cat, and average current density up to 1 A cm−2 at −1.5 V vs. SCE potential after 2 h electrolysis. The recycled electrolysis experiment confirms its good stability and practical potential.

Cu-Bi Bimetallic Catalysts Derived from Metal-Organic Framework Arrays on Copper Foam for Efficient Glycine Electrosynthesis.

Glycine as one of the most abundant amino acids in human proteins, with extensive applications in both life and industry, is conventionally synthesized through complex procedures or toxic feedstocks. In this study, we present a facile and benign electrochemical pathway for synthesis of glycine through reductive coupling of glyoxylic acid and nitrate over a copper-bismuth bimetal catalyst derived from a metal-organic framework (MOF) array on copper foam (Cu/Bi-C@CF). Remarkably, Cu/Bi-C@CF achieves a fantastic selectivity of 89%, corresponding a high Faraday efficiency of 65.9%. From control experiments, introduction of Bi caused the binding energy of Cu shift to lower state, which leads to a high selectivity towards the formation of key hydroxylamine intermediate rather than ammonia product, facilitating the formation of oxime and providing additional sites for subsequent hydrogenation reaction on the way to glycine. Moreover, the MOF array derivation ensures the effective dispersion of Bi and enhances the stability of Cu/Bi-C@CF. This innovative approach not only presents sustainable pathways for the production of value-added organonitrogen compounds utilizing readily available carbon and nitrogen sources, but also provides novel insights into the design of multistage structural catalysts for sequential reactions.

295 Synthesis of glycine from trans-4-hydroxy-L-proline in tissues of juvenile hybrid striped bass (Morone chrysops x M. Saxatilis)

Abstract Trans-4-Hydroxy-L-Proline (Hyp) is a major amino acid in the collagen of fish. The turnover of collagen in various tissues releases a large amount of Hyp, which has traditionally been considered as a metabolic waste. However, results of recent studies have identified the conversion of Hyp into glycine in piglets. The present study tests this hypothesis that hybrid striped bass (HSB, a carnivorous fish species) can form glycine from Hyp. Fish were fed a standard diet containing 60% fishmeal for 10 wk and grew from 5.5 to 45 g during a 9-wk period. Slices (~75 mg) of skeletal muscle, liver, proximal intestine, gills, and brain were obtained from 45-g HSB (n = 6) and incubated at 26 °C for 2 h in 1 mL of oxygenated (95% O2/5% CO2) Krebs-Henseleit bicarbonate buffer (pH 7.4, with 5 mM D-glucose) containing 0, 0.2, or 2 mM Hyp. After a period of 2 h incubation, 200 μL of 1.5 M HClO4 was added into the incubation medium to stop the reaction. The acidified medium plus tissue together was homogenized and the homogenizer was rinsed with 1 mL of water, followed by the addition of 100 μL of 2 M K2CO3. The neutralized extract was analyzed for amino acids using HPLC involving o-phthaldialdehyde derivatization. Tissues without incubation were also determined for amino acids. Data were statistically analyzed by a paired t-test. Glycine was produced from 0.2 and 2 mM Hyp by the liver and skeletal muscle, and 2 mM Hyp by the intestine (Table 1). Glycine was further converted into serine in the liver, but not skeletal muscle or intestine. The production of glycine or serine from Hyp was not due to net protein breakdown in tissues. Tyrosine was measured as an indicator of protein degradation. There was no detectable generation of glycine from 0.2 or 2 mM Hyp by the gills or brain of HSB. These results indicate the synthesis of glycine from Hyp by juvenile HSB in a tissue-specific manner. Because skeletal muscle accounts for ~45% of the body weight, this organ is the major site for this metabolic pathway in the fish. (Supported by USDA/NIFA grant No. 2022-67015-36200)

237 Increasing the threonine-to-lysine ratio improves the growth performance of slow-growing pigs when fed with precision feeding techniques

Abstract Individual precision feeding (IPF) is a suitable tool to account for the nutritional requirement variability among pigs. It was previously reported that, within IPF, pigs require greater Thr:Lys than conventional group-phase feeding (GPF) pigs. It remains unknown if these differences in Thr:Lys requirements occur due to different growth rates (Gr). This study evaluated whether the Thr:Lys requirements of pigs fed with IPF systems are affected by Gr. Sixty pigs (30 barrows and 30 gilts) with 38.1 ± 3.8 kg of body weight were distributed in a completely randomized 3 × 5 factorial arrangement. Pigs were classified into fast (FGr), medium (MGr) and slow (SGr) Gr based on their average daily gain (ADG) during 6 wk previous to the trial. After classification, pens with 2 barrows and 2 gilts from the same Gr group were randomly assigned to one of five treatments (12 repetitions per treatment). Treatments consisted of a conventional GPF (GPF100) receiving 100% of the optimal 0.65 Thr:Lys and 4 IPF treatments providing 140% (IPF140), 120% (IPF120), 100% (IPF100) and 80% (IPF80) of the optimal ratio. GPF100 pigs were fed a single diet with 0.97% standardized ileal digestible Lys. IPF diets of the pigs were adjusted every 2 d to meet the Lys requirements of the most demanding pig in the pen. Body weight was recorded twice a week, and individual feed intake (ADFI) daily over 21 d. At d 1 and 21, pigs were scanned with dual X-ray to estimate their body composition. Body weight, body protein and lipid masses were analyzed as repeated measures over time. The Dunnett test was used to compare the IPF treatments to GPF100 and the Tukey test to compare Gr groups. The pig was considered the experimental unit. FGr maintained greater (treatment × Gr, P < 0.05) ADFI and ADG and greater (P < 0.05) lipid deposition over the trial when compared with MGr and SGr. However, increasing Thr:Lys enhanced (P < 0.05) ADG and ADFI of SGr pigs within IPF, resulting in similar (P > 0.05) values between Gr groups in IPF120 and IPF140. Although FGr tended (P = 0.05) to have greater final body protein mass, SGr presented leaner gain (P < 0.05), independently of the Thr:Lys. Threonine supplementation supports metabolic processes like glycine and serine synthesis, impacting gut health, protein synthesis, energy production, and oxidative stress, potentially explaining lower lipid deposition in SGr pigs when the same level of energy in the diet. SGr pigs might need a different AA profile where a higher Thr:Lys ratio likely enhances the metabolic capacity to support fast growth in SGr pigs within IPF. Consequently, increasing the Thr:Lys ratio within IPF led to improved growth performance in SGr pigs.

384 Synthesis of glycine from trans-4-hydroxy-L-proline by placentae but not endometria of gestating gilts

Abstract Trans-4-hydroxy-L-proline (Hyp) is an abundant amino acid in the collagen of pigs. The turnover of this protein releases a large amount of Hyp, traditionally considered a metabolic waste. However, results of recent studies documented the conversion of Hyp into glycine in young pigs. Because pregnant gilts are typically fed a soybean meal-based diet that contains insufficient glycine and provides only 35% of the total glycine needed by pregnant gilts, it is possible that the conceptus can form glycine from Hyp. This hypothesis was tested in the present study. Gilts were fed a 1.8-kg corn- and soybean meal-based diet containing 14% crude protein. On d 90 of gestation, gilts (n = 5) were hysterectomized after euthanasia. Slices (~ 100 mg) of placentae or endometria were incubated at 37 °C for 2 h in oxygenated (95% O2/5% CO2) Krebs-Henseleit bicarbonate buffer (pH 7.4, with 5 mM D-glucose) containing 0 or 2 mM Hyp. After a period of 2 h incubation, 200 μL of 1.5 M HClO4 was added into the incubation medium to stop the reaction. The tissues were homogenized and rinsed with 1 mL water, followed by the addition of 100 μL of 2 M K2CO3. The neutralized extract was analyzed for amino acids using HPLC involving derivatization with o-phthaldialdehyde. Tissues that received no incubation time were determined as well. Data were analyzed by the paired t-test. Results indicated that glycine was produced from 2 mM Hyp by the placenta (Table 1). Glycine was subsequently converted into serine by the placenta. The formation of glycine and serine from Hyp was not due to protein breakdown because there were no differences (P > 0.05) in concentrations of tyrosine (an amino acid that is neither synthesized nor degraded by porcine placentae) in the incubation medium plus tissue at the end of a 2-h incubation period. In contrast to placentae, endometria did not form glycine or serine from Hyp. These findings indicate an important role for Hyp in the provision of both glycine and serine in the conceptus, which may be nutritionally and physiologically significant to compensate for a deficiency of glycine in maternal diets for gestating gilts. (Supported by a USDA/NIFA grant # 2022-67015-36376 and USDA multistate Hatch project #7752: S1081)

Oriented Synthesis of Glycine from CO2, N2, and H2O via a Cascade Process.

Air contains carbon, hydrogen, oxygen, and nitrogen elements that are essential for the constitution of amino acids. Converting the air into amino acids, powered with renewable electricity, provides a green and sustainable alternative to petrochemical-based methods that produce waste and pollution. Here, taking glycine as an example, we demonstrated the complete production chain for electrorefining amino acids directly from CO2, N2, and H2O. Such a prospective scheme was composed of three modules, linked by a spontaneous C-N bond formation process. The high-purity bridging intermediates, separated from the stepwise synthesis, boosted both the carbon selectivity from CO2 to glycine of 91.7% and nitrogen selectivity from N2 to glycine of 98.7%. Under the optimum condition, we obtained glycine with a partial current density of 160.8 mA cm-2. The high-purity solid glycine product was acquired with a separation efficiency of 98.4%. This work unveils a green and sustainable method for the abiotic creation of amino acids from the air components.

Computational Insights for Electrocatalytic Synthesis of Glycine

Computational Insights for Electrocatalytic Synthesis of Glycine

A New Route to the Prebiotic Synthesis of Glycine via Ab Initio-Based Machine Learning Calculations.

In this work, we study the synthesis of glycine, the simplest amino acid, using ab initio molecular dynamics and enhanced sampling techniques to explore and quantify novel potential pathways. Our protocol integrates state-of-the-art machine learning approaches, allowing us to sample relevant chemical spaces more efficiently. We discover a novel "oxyglycolate path", distinct from the "standard" Strecker mechanism, identify new intermediates, and provide a full thermodynamic characterization of all reaction steps. This alternative pathway aligns better with meteoritic and experimental observations, paving the way for further investigations. Integrating quantum accuracy and machine learning in prebiotic chemistry represents a methodological milestone advancing the exploration of life's prebiotic origins.

Photocatalytic Synthesis of Glycine from Methanol and Nitrate.

Photocatalytic utilization of methanol and nitrate as carbon and nitrogen sources for the direct synthesis of amino acids could provide a sustainable way for the valorization of green "liquid sunlight" and nitrate waste. In this study, we developed an efficient photochemical method to synthesize glycine directly from methanol and nitrate, which cascades the C-C coupling to form glycol, nitrate reduction to NH3, and finally C-N coupling to generate glycine. Interestingly, the involved photocatalytic tandem reactions show a synergistic effect, in which the presence of nitrate is the dominant factor to enable the overall reaction and reach high synthetic efficiency. Ba2+-TiO2 nanoparticles are confirmed as a feasible and efficient catalyst system for the photosynthesis of glycine with a remarkable glycine photosynthesis rate of 870 μmol gcat-1 h-1 under optimal conditions. This work establishes a novel catalytic system for amino acid synthesis from methanol and nitrate under mild conditions. These results also allow us to further suppose the formation pathways of amino acids on the primitive earth, as an extension to proposals based on the Miller-Urey experiments.

Preparation of copper glycinate and study of its effect on the germination of winter barley seeds

We analyzed the encrustation of winter barley seeds, which includes its preliminary treatment with cuprum glycinate, with the purpose of increasing yield and biochemical indicators of grain, and also improving the ecological condition of the soil. The objective of the research was to select methods for the synthesis of cuprum glycinate, study its chemical composition and the possibility of using this compound as a chelated micro-fertilizer for pre-sowing encrustation of winter barley seed as part of a tank mixture. Two well-known synthesis methods were used to obtain cuprum glycinate. The first method was the interaction between CuO with a solution of glycine during heating, during which pink metallic copper inclusions were noticed in the mixture of reaction products. It was found that it is expedient to synthesize the glycine complex of cuprum by the reaction of a suspension of Cu2CO3(OH)2 with glycine during heating (the yield is 97%), since a complex compound Cu(NH2CH2COO)2•H2O of sufficient purity is formed. The composition of the synthesized substance and the confirmation of the formula of the compound Cu(NH2CH2COO)2•H2O were obtained by determining the infrared and the atomic absorption spectrum of the aqueous solution. Based on the obtained differences in the atomic absorption spectra of the synthesized copper sulfate and copper glycinate the formation of the latter was confirmed. The IR spectrum confirms the formula of the complex compound and the formation of strong covalent bonds between the metal cation and the ligands. The study of the effect of cuprum glycinate on the germination of winter barley Tutankhamun seeds was carried out in comparison with the similar effect of a complex compound of cuprum with ethylenediaminetetraacetate. The study of the influence of cuprum glycinate on the germination of winter barley revealed positive results in which the germination exceeded the control by 9–27%. Winter barley seeds treated with distilled water served as a control. Treatment of winter barley seeds with an aqueous solution of cuprum glycinate in the amount of 20 g of cuprum per 1 ton of grain led to better germination than pre-treatment of seeds with a twice concentrated corresponding solution. Treatment with a complex compound of copper with ethylenediaminetetraacetate had no significant effect on the germination and characteristics of sprouts. The results of laboratory studies confirmed the feasibility of using complex compounds of biometal copper with organic chelating ligands as microfertilizers for pre-sowing seed encrustation, as they have high stability and sufficient solubility in water, are non-toxic, are better absorbed by plants and are considered cost-effective and environmentally safe.

ATF4 and mTOR regulate metabolic reprogramming in TGF-β-treated lung fibroblasts.

Idiopathic pulmonary fibrosis is a fatal disease characterized by the TGF-β-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive replacement of healthy lung with scar tissue. We and others have shown that fibroblast activation is supported by metabolic reprogramming, including the upregulation of the de novo synthesis of glycine, the most abundant amino acid found in collagen protein. How fibroblast metabolic reprogramming is regulated downstream of TGF-β is incompletely understood. We and others have shown that TGF-β-mediated activation of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and downstream upregulation of Activating Transcription Factor 4 (ATF4) promote increased expression of the enzymes required for de novo glycine synthesis; however, whether mTOR and ATF4 regulate other metabolic pathways in lung fibroblasts has not been explored. Here, we used RNA sequencing to determine how both ATF4 and mTOR regulate gene expression in human lung fibroblasts following TGF-β. We found that ATF4 primarily regulates enzymes and transporters involved in amino acid homeostasis as well as aminoacyl-tRNA synthetases. mTOR inhibition resulted not only in the loss of ATF4 target gene expression, but also in the reduced expression of glycolytic enzymes and mitochondrial electron transport chain subunits. Analysis of TGF-β-induced changes in cellular metabolite levels confirmed that ATF4 regulates amino acid homeostasis in lung fibroblasts while mTOR also regulates glycolytic and TCA cycle metabolites. We further analyzed publicly available single cell RNAseq data sets and found increased expression of ATF4 and mTOR metabolic targets in pathologic fibroblast populations from the lungs of IPF patients. Our results provide insight into the mechanisms of metabolic reprogramming in lung fibroblasts and highlight novel ATF4 and mTOR-dependent pathways that may be targeted to inhibit fibrotic processes.

Stabilized Carbon-Centered Radical-Mediated Carbosulfenylation of Styrenes: Modular Synthesis of Sulfur-Containing Glycine and Peptide Derivatives.

Sulfur-containing amino acids and peptides play critical roles in organisms. Thiol-ene reactions between the thiol residues of L-cysteine and the alkenyl fragments in the designed coupling partners serve as primary tools for constructing C─S bonds in the synthesis of unnatural sulfur-containing amino acid derivatives. These reactions are favored due to the preference for hydrogen transfer from thiol to β-sulfanyl carbon radical intermediates. In this paper, the study proposes utilizing carbon-centered radicals stabilized by the capto-dative effect, generated under photocatalytic conditions from N-aryl glycine derivatives. The aim is to compete with the thiol hydrogen, enabling radical C─C bond formation with β-sulfanyl carbon radicals. This protocol is robust in the presence of air and water, offers significant potential as a modular and efficient platform for synthesizing sulfur-containing amino acids and modifying peptides, particularly with abundant disulfides and styrenes.

Revealing the endogenous homoserine cycle for the effective methanol conversion in Pichia pastoris

Methanol, being electron rich and derivable from methane or CO2, is a very promising feedstock for biomanufacturing. Nevertheless, challenges still remain in methanol metabolism for value-added chemicals overproduction. Here, we performed gene mining and revealed the endogenous homoserine cycle for methanol conversion in Pichia pastoris for the first time. In addition, by manipulation of the concentration of methanol, adding the amino acids, and overexpressing the pathway genes, we identified the key substrates and rate-limiting enzymes (SDA and TS) affecting the homoserine cycle. Hence, the metabolic fluxes were rewired toward homoserine cycle and the methanol conversion was stepwise promoted through the introduction of cytoplasmic methanol oxidation pathway, overexpression of the key genes in the glycine and serine synthesis routes, and multicopy integration of the SDA and TS expression cassettes. Eventually, in combination with pathway revelation and metabolic engineering, the rebuilding methylotroph with strengthened homoserine cycle was able to produce 33.9 mg/L/OD β-carotene with a titer of 173.9 mg/L from methanol. The unit cell titer of β-carotene was 145.7 % higher than that of the initial strain (Kp16). This study will lay a good foundation for optimizing methylotrophic platform to promote industrial utilization.

Mechanisms of interstellar synthesis of glycine, alanine, and serine from aminonitriles, OH, and H2O

AbstractA new potential energy surface for forming glycine in the gas phase, starting from association of aminoacetonitrile (NH2CH2CN) with OH followed by subsequent hydrolysis, was determined using CBS‐QB3 calculation. The overall activation energy was 90 kJ mol−1 or 0 without or with catalytic H2O, respectively. Alanine or serine was formed from 2‐aminopropionitrile (CH3CH(NH2)CN) or 2‐amino‐3‐hydrxypropionitrile (HOCH2CH(NH2)CN) instead of aminoacetonitrile with the overall activation energies of 89 or 49 kJ mol−1, respectively. When an additional H2O was involved in each reaction as a catalyst, barrierless reaction pathways were obtained. These results suggest that it is possible for investigated reactions to occur in interstellar ices along the proposed pathways, taking kinetic aspects into account.

The anti-depression effect and potential mechanism of the petroleum ether fraction of CDB: Integrated network pharmacology and metabolomics

The combination of Chaidangbo (CDB) is an antidepressant traditional Chinese medicine (TCM) prescription simplified by Xiaoyaosan (a classic antidepressant TCM prescription) through dismantling research, which has the effect of dispersing stagnated liver qi and nourishing blood in TCM theory. Although the antidepressant effect of CBD has been confirmed in animal studies, the material basis and possible molecular mechanism for antidepressant activity in CBD have not been clearly elucidated. Herein, we investigated the effects and potential mechanisms of CDB antidepressant fraction (petroleum ether fraction of CDB, PEFC) on chronic unpredictable mild stress (CUMS)-induced depression-like behavior in mice using network pharmacology and metabolomics. First, a UPLC-QE/MS was employed to identify the components of PEFC. To extract active ingredients, SwissADME screening was used to the real PEFC components that were found. Potential PEFC antidepressant targets were predicted based on a network pharmacology approach, and a pathway enrichment analysis was performed for the predicted targets. Afterward, a CUMS mouse depression model was established and LC-MS-based untargeted hippocampal metabolomics was performed to identify differential metabolites, and related metabolic pathways. Finally, the protein expressions in mouse hippocampi were determined by Western blot to validate the network pharmacology and metabolomics deduction. A total of 16 active compounds were screened in SwissADME that acted on 73 core targets of depression, including STAT3, MAPKs, and NR3C1; KEGG enrichment analysis showed that PEFC modulated signaling pathways such as PI3K-Akt signaling pathway, endocrine resistance, and MAPK to exert antidepressant effects. PEFC significantly reversed abnormalities of hippocampus metabolites in CUMS mice, mainly affecting the synthesis and metabolism of glycine, serine, and threonine, impacting catecholamine transfer and cholinergic synapses and regulating the activity of the mTOR signaling pathway. Furthermore, Western blot analysis confirmed that PEFC significantly influenced the main protein levels of the PI3K/Akt/mTOR signaling pathways in the hippocampus of mice subjected to CUMS. This study integrated metabolomics, network pharmacology and biological verification to explore the potential mechanism of PEFC in treating depression, which is related to the regulation of amino acid metabolism dysfunction and the activation of PI3K/Akt/mTOR signaling pathways in the hippocampus. The comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in TCM with antidepressant effect.

Highly Efficient Electrosynthesis of Glycine over an Atomically Dispersed Iron Catalyst.

Glycine is a nonessential amino acid that plays a vital role in various biological activities. However, the conventional synthesis of glycine requires sophisticated procedures or toxic feedstocks. Herein, we report an electrochemical pathway for glycine synthesis via the reductive coupling of oxalic acid and nitrate or nitrogen oxides over atomically dispersed Fe-N-C catalysts. A glycine selectivity of 70.7% is achieved over Fe-N-C-700 at -1.0 V versus RHE. Synergy between the FeN3C structure and pyrrolic nitrogen in Fe-N-C-700 facilitates the reduction of oxalic acid to glyoxylic acid, which is crucial for producing glyoxylic acid oxime and glycine, and the FeN3C structure could reduce the energy barrier of *HOOCCH2NH2 intermediate formation thus accelerating the glyoxylic acid oxime conversion to glycine. This new synthesis approach for value-added chemicals using simple carbon and nitrogen sources could provide sustainable routes for organonitrogen compound production.