High Concentrations Of Glycine Research Articles

Glycine restores the sensitivity to antibiotics in multidrug-resistant bacteria.

The management of infections caused by multiresistant bacteria has become of fundamental importance for any medical practice. Glycine is the most common and the simplest non-essential amino acid in humans. Glycine is very effective in improving health and supporting growth and wellbeing of humans and animals. Instead, for many bacteria, high concentrations of glycine induce lysis or deep morphological alterations. The effect of glycine on multidrug resistant (MDR) microorganisms has not yet been extensively researched. The present study was conducted 1) to establish the effect of glycine on different nosocomial pathogens isolated during routine diagnostic investigations; 2) to determine the minimum inhibitory concentration of glycine and the type of activity performed (bacteriostatic or bactericidal) on representative isolates; 3) to test the interaction between glycine and meropenem, cefiderocol, or colistin. The data reported here show a dose-dependent activity of glycine on bacteria and its bactericidal activity on MDR bacteria. Furthermore, we found that the action of glycine restores in vitro the susceptibility of multiresistant nosocomial pathogens to the tested antibiotics.IMPORTANCEAntimicrobial resistance is a constantly growing concern throughout the world, and Italy is among the Western countries where antimicrobial resistance is most widespread. In Tuscany, carbapenemase-producing Enterobacterales are now even endemic. In this study, we challenged some resistant bacteria with a well-known molecule, glycine, the antibacterial properties of which have been known since the past century. This study could bring new insights into combining antibiotics with the simplest of all amino acids. The restoration of sensitivity to the aforementioned antibiotics by a natural compound, already used for clinical purposes, is of extreme importance in an era of proliferation of multiresistant bacteria. The in vivo use of this amino acid in evaluating its effectiveness against infections should be investigated. The low cost of this molecule can also make it easy to use even in low-income countries.

Longitudinal characterization of serum metabolome and lipidome reveals that the ceramide profile is associated with metabolic health in early postpartum cows experiencing different lipolysis

Reduced feed intake in early lactation prompts increased fat mobilization to meet dairy cows' energy needs for milk production. The increased lipolysis in cows presents significant health risks with unclear mechanisms. The objectives of our study were to compare the longitudinal profiles of metabolites and lipids of serum from high and low-lipolysis cows. Forty multiparous Holstein dairy cows were enrolled in the retrospective study. Serum samples were collected on d 7 before expected calving, as well as on d 5, d 7, d 14, and d 21 postpartum. Dairy cows were grouped according to mean serum nonesterified fatty acids on d 5 and 7 after parturition as low (<0.600 mmol/L; n = 8; LFM) and high (>0.750 mmol/L; n = 8; HFM), indicating fat mobilization during early lactation. Lactational performance and serum metabolic parameters related to glucose and lipid metabolism, liver functions, oxidative status, and inflammatory responses were determined. Serum samples were subjected to LC-MS-based metabolomics and lipidomics. Despite differences in postpartum BW change, there were no observed variations in milk yield and composition between 2 groups. Serum BHBA, glucose, leptin, aspartate aminotransferase, IL-6, and TNF-α were greater in cows with HFM than in LFM. Serum adiponectin, revised quantitative insulin sensitivity check index and albumin were lower in cows with HFM than LFM. Intensified fat mobilization in the HFM cows came along with reduced estimated insulin sensitivity, impaired liver functions, and increased oxidative stress and inflammatory responses. Differences in metabolic patterns were observed across the transition period when comparing serum blood matrices (e.g., in different amino acids, acylcarnitines, and sphingolipids). The serum metabolome of the HFM cows was characterized by higher concentrations of glycine, acylcarnitines, carnosine, Cer(d20:0/18:0), Cer(d18:1/16:0), and Cer(t18:0/24:0) compared with LFM. The differential serum metabolites and lipids at different sampling times during the peripartum period were enriched in the sphingolipid metabolism. Differences in serum metabolic status parameters suggest that cows adopt varied metabolic adaptation strategies to cope with energy deficits postpartum. Our investigation found a comprehensive remodeling of the serum metabolic profiles in transition dairy cattle, highlighting the significance of alterations in sphingolipid species, as they play a crucial role in insulin resistance and metabolic disorders.

Enzymatic Hydrolysis of Protein Hydrolysate from Pangasius sp. by-Product using Bromelain

Fish protein hydrolysate (FPH) is a product resulting from the degradation of fish protein into simple peptides and amino acids through hydrolysis. This study aims to optimise the enzymatic hydrolysis conditions of Pangasius sp. by-products to produce high-quality fish protein hydrolysate. Bromelain enzyme was used as the catalyst for hydrolysis. The degree of hydrolysis (DH), pH and antioxidant activity of FPH were used as response parameters. The optimisation was done using response surface methodology (RSM) by applying two factors (enzyme concentration and incubation time) with a 3-level Central Composite Design (CCD) model. The result showed that the bromelain concentration and incubation time of catfish protein hydrolysate gave significantly different effects (p&lt;0.05) on the response parameters of Pangasius protein hydrolysate. Hydrolysis of Pangasius protein with 0.04% bromelain enzyme and incubation time of 2.8 hours resulted in DH, pH and DPPH antioxidant activity of 35.88%, 7.07 and 29.86%, respectively. The response value of Pangasius protein hydrolysate was within the range of the predicted value of hydrolysate. Therefore, the optimum conditions suggested by RSM can be used in the future production of Pangasius FPH. In addition, amino acid profiles of Pangasius protein hydrolysate showed high concentrations of Glycine, L-glutamic acid and L-aspartic Acid.

PSI-14 Weaning Stress Increases Bile Cysteine and Cysteinylglycine Concentrations in Pigs

Abstract Weaning is a critical time for pigs that is associated with nutritional, social, and environmental stressors that lead to reduced feed intake and poor nutrient utilization. Cysteine is a sulfur amino acid and a key constituent of glutathione (GSH), a major intracellular antioxidant and potential regulator of intestinal redox status. Glutathione is present in biliary secretions and may be an important source of cysteine to intestine in newly weaned pigs. The objective of this study was to determine amino thiol and amino acid concentrations in bile. Piglets (initial BW = 7,233 ± 683 g) were either weaned on day 21 of age (W; n = 9) and euthanized after 2 d or remained on the sow until day 23 of age (NW; n = 9) and were euthanized. Weaned pigs were fasted and allowed free access to water. After euthanasia, bile (directly from the gallbladder), jejunum, and ileum samples were collected. Bile amino acids and bile amino thiols were analyzed by reversed phase HPLC following precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate and 4-fluoro-7-aminosulfonylbenzofurazan, respectively. Reverse transcription quantitative real-time PCR was performed to measure cysteine transporter expression in jejunum and ileum. Cysteine concentration was greater in W than NW pigs (1,203 versus 324 ± 99 µmol/L; P &amp;lt; 0.0001). Both γ-glutamylcysteine (7.1 versus 2.2 ± 2.1 µmol/L), the direct precursor for GSH synthesis, and cysteinylglycine (203 versus 110 ± 30 µmol/L, the direct product of GSH degradation, were greater in W pigs than in NW pigs (P &amp;lt; 0.05). Bile GSH concentration tended to be greater in W than NW pigs (9.1 versus 5.3 ± 2.8 µmol/L; P = 0.07). Taurine, derived from cysteine oxidation, was greater in W than NW pigs (180 versus 91 ± 23 µmol/L; P &amp;lt; 0.05), whereas glutamate (11.4 versus 8.8 ± 1.9 µmol/L) and glycine (463 versus 403 ± 62 µmol/L), additional amino acid constituents of GSH, were not different between groups (P &amp;gt; 0.10). Expression of cysteine transporters SLC1A4, SLC1A5, SLC6A14, SLC6A19, SLC7A9, and SLC7A11 in jejunum and ileum were not different between groups (P &amp;gt; 0.10). Despite no feed intake after weaning, cysteine concentrations increase in bile. While this is likely due to bile accumulation in the gallbladder after weaning, high bile cysteine, cysteinylglycine, and glycine concentrations could potentially be a source of these amino acids for enterocytes during weaning stress.

Effects of Glycine Supplementation in Drinking Water on the Growth Performance, Intestinal Development, and Genes Expression in the Jejunum of Chicks.

Glycine, the most basic amino acid found in nature, is considered an essential amino acid for chicks. However, the precise understanding of high concentrations of glycine's significance in promoting the growth performance of chicks, as well as its impact on intestinal development, re-mains limited. Consequently, the objective of this study was to investigate the effects of glycine supplementation in drinking water on growth performance, intestine morphology, and development in newly hatched chicks. In this study, 200 newly born chicks were selected and pro-vided with a supplementation of 0.5%, 1%, and 2% glycine in their drinking water during their first week of life. The results revealed that glycine supplementation in drinking water could significantly increase the average daily gain of chicks from days 7 to 14. Furthermore, a significant difference was observed between the group supplemented with 1% glycine and the control group. Concurrently, this glycine supplementation increased the villus height and the ratio of the villus height to crypt depth in jejunum on both day 7 and day 14. Glycine supplementation in drinking water significantly affected the mRNA expression level of the ZO-1, GCLM, and rBAT genes in jejunum, which may have certain effects on the mucosal immune defense, cellular antioxidant stress capacity, and amino acid absorption. Overall, the findings of this study indicate that glycine supplementation in drinking water can enhance the growth performance of chicks and promote their intestine development.

The effect of enzyme hydrolysis on collagen raw materials of animal origin

During the processing of meat, a significant part of the offal is thrown away as waste or used for low-value products. Meat by-products (for example, legs with a putty joint) are good sources for obtaining protein hydrolysate, since they are produced in large quantities and are rich in proteins. In order for these by-products to be advantageously processed into valuable products by enzymatic hydrolysis, protein hydrolysate was obtained from wool by-products. Protein hydrolysate is a promising food ingredient for the development of functional food products. To obtain protein hydrolysate, an enzyme preparation was selected and the parameters of hydrolysis (concentration, duration) were determined. The physicochemical, microbiological properties of protein hydrolysate were investigated for use in the production of meat products of the herodietic direction. The data obtained showed that hydrolysates from beef legs contain a high concentration of glycine – 27.160 ± 9.235%, valine and proline showed almost the same high level – 17.284 ± 6.914 16.667 ± 4.333%, alanine – 10.494 ± 2.728%, arginine – 6.173 ± 2.469%. Studies of the mineral composition of the finished protein hydrolysate showed the concentration of macro and microelements: calcium - 0.93±0.005 mg/100 g, magnesium - 0.27±0.005 mg/100 g and zinc - 0.07±0.001 mg/100 g. A technological scheme for obtaining protein hydrolysate from wool by-products has been developed and proposed. The effectiveness of the use of 1% BLT 7 as an enzyme preparation providing hydrolysis of beef leg proteins with a put joint is substantiated.

Obtaining protein hydrolysate from secondary meat raw materials for food enrichment

Diseases of the musculoskeletal system are the most common in the elderly. Collagen hydrolysates obtained from animal raw materials are widely used to prevent and reduce the risk of such diseases. The effectiveness of collagen hydrolysates as an independent product and as part of food products has been confirmed. A study of the technological process of obtaining hydrolysates from inexpensive raw materials, such as wool by-products, using enzymatic hydrolysis. The main purpose of the study was to identify factors affecting the accumulation of hydrolysis products. To achieve this goal, the main parameters of hydrolysis were optimized, including the duration of the process, the temperature regime and the amount of enzyme added in the process. The resulting protein hydrolysate contains a high concentration of glycine – 27,160 %, 13,317 %, 13,216 %, valine and proline showed almost the same high level – 16 %, 10 %, 8,8 %, alanin – 10,494 %, 7,022 %, 6,681 %, arginine – 6,173%, 3,874%, 6,021% depending on raw materials. The results of the studies showed that the optimal parameters for obtaining hydrolysate were achieved using an enzyme preparation in an amount of 5% of the total mass, temperature 45 ° C, duration of hydrolysis 24 hours. The hydrolysate obtained as a result of this process can serve as the basis for the production of functional products that are intended for the elderly.

Chemical-Structural Identification of Crude Gelatin from Jellyfish (Stomolophus meleagris) and Evaluation of Its Potential Biological Activity

The demand for jellyfish is growing worldwide, especially due to their high nutraceutical value. In this study, the extraction and characterization of crude gelatin from the brown cannonball jellyfish (Stomolophus meleagris), which is periodically found in large volumes on the American Pacific coasts, were carried out. The crude gelatin obtained by alkaline treatment, with subsequent heat and dialysis treatment, showed an ability to quench free radicals (via ABTS and ORAC methods), and protect human cells against oxidative damage (through inhibition of hemolysis by AAPH), and they protected against mutations caused by aflatoxin B1 in the Salmonella enterica Typhimurium TA100 strain. Furthermore, it was established that these extracts were innocuous for eukaryotic cells (genotoxicity assay). The amino acid profiles indicate a high concentration of glycine and proline, as well as charged amino acids. Electrophoretic, FT-IR, and 1H-NMR studies indicated that one of the main proteins present in this crude gelatin is collagen. The presence of collagen and other proteins was identified by proteomic studies. Alkaline crude gelatin from brown jellyfish could be considered as potential candidates to be evaluated as antioxidant agents in foods in future research.

Withdrawn: Glycine transporter 1 (GlyT1) is a novel therapeutic target for Alzheimer’s disease

Withdrawal: Miran Yoo, Seong Muk Kim, Juho Lee, Hye‐Ju Kim, Seong Jeong Park “Glycine transporter 1 (GlyT1) is a novel therapeutic target for Alzheimer's disease” Alzheimer's &amp; Dementia, Volume 18, Supplemental Issue 10.The above abstract, published online on 20th December 2022, on Wiley Online Library (https://alz‐journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.064468) has been withdrawn by agreement between the authors, the Senior Director of Scientific Programs and Outreach, Claire Sexton, the Director of Scientific Programs at the Alzheimer's Association, Ozama Ismail, and John Wiley &amp; Sons Inc. The abstract has been withdrawn at the authors’ request because the authors did not have Amyloid Solution's authorization to publish the information contained in it.

CycA-Dependent Glycine Assimilation Is Connected to Novobiocin Susceptibility in Escherichia coli.

Escherichia coli serine hydroxymethyltransferase (GlyA) converts serine to glycine, and glyA mutants are auxotrophic for glycine. CycA is a transporter that mediates glycine uptake. Deleting glyA in E. coli strain W3110 led to activation of CysB, which was related to novobiocin (NOV) susceptibility. Moreover, deleting glyA resulted in increased sensitivity to NOV, and this could be reversed by high concentrations of glycine. Reverse mutants of ΔglyA were selected and one of them had a mutation in yrdC, the gene encoding threonylcarbamoyl-AMP synthase. Subsequent proteome analysis showed that deleting glyA led to increased expression of TcyP and TdcB, making this bacterium dependent on CycA for glycine assimilation. Furthermore, deleting cycA in a ΔglyA background caused a severe growth defect on Luria-Bertani medium, which could be complemented by high concentrations of exogenous glycine. Mutation of yrdC led to decreased expression of TdcB but increased expression of ThrA/B/C and LtaE, which favored the conversion of threonine to glycine and thus avoided the dependence on CycA. Correspondingly, deleting of tcyP, tdcB, or gshA could reverse the NOV-sensitive phenotype of ΔglyA mutants. Overexpression of cycA resulted in increased sensitivity to NOV, whereas deleting this gene caused NOV resistance. Moreover, overexpression of cycA led to increased accumulation of NOV upon drug treatment. Therefore, inactivation of glyA in E. coli led to CycA-dependent glycine assimilation, which enhanced the accumulation of NOV and then made the bacterium more sensitive to this drug. These findings broaden our understanding of glycine metabolism and mechanisms of NOV susceptibility. IMPORTANCE Novobiocin (NOV) has been used in clinical practice as an ATPase inhibitor for decades. However, because it has been withdrawn from the market, pharmaceutical companies are searching for other ATPase inhibitors. Thus, probing the mechanisms of susceptibility to NOV will be beneficial to those efforts. In this study, we showed that inactivation of glyA in E. coli led to CycA-dependent glycine assimilation, which accompanied the accumulation of NOV and thereby increased the sensitivity to this drug. To date, this is the first report demonstrating the linkage between glycine assimilation and NOV susceptibility, and it is also the first report showing that YrdC is able to modulate the metabolic flux of threonine.

Metabolomic Profiles Associated with Obesity and Periodontitis during Pregnancy: Cross-Sectional Study with Proton Nuclear Magnetic Resonance (1H-NMR)-Based Analysis.

This study aimed to elucidate the metabolomic signature associated with obesity and periodontitis during pregnancy in plasma and saliva biofluids. Ninety-eight pregnant women were divided into: with obesity and periodontitis (OP = 20), with obesity but without periodontitis (OWP = 27), with normal BMI but with periodontitis (NP = 21), with normal BMI and without periodontitis (NWP = 30). Saliva and plasma were analyzed by 1H-NMR for metabolites identification. Partial Least Squares-Discriminant Analysis (PLS-DA), Sparse PLS-DA (sPLS-DA), and Variable Importance of Projection (VIP) were performed. ANOVA and Pearson's correlation were applied (p &lt; 0.05). Plasmatic analysis indicated the levels of glucose (p = 0.041) and phenylalanine (p = 0.015) were positively correlated with periodontal parameters and BMI, respectively. In saliva, periodontitis was mainly associated with high levels of acetic acid (p = 0.024), isovaleric acid, butyric acid, leucine, valine, isoleucine, and propionic acid (p &lt; 0.001). High salivary concentrations of glycine (p = 0.015), succinic acid (p = 0.015), and lactate (p = 0.026) were associated with obesity. Saliva demonstrated a more elucidative difference than plasma, indicating the glucose-alanine cycle, alanine metabolism, valine, leucine and isoleucine degradation, glutamate metabolism, and Warburg effect as the main metabolic pathways.

Modulation of NMDA receptor activity by CR4056, an imidazoline-2 receptor ligand with analgesic properties.

CR4056 is an imidazoline-2 receptor ligand having potent analgesic activity and synergistic effect with opioids. Very recently it has been found that CR4056 can revert the cognitive impairment in animal models of Alzheimer's disease (AD). Since several lines of evidence highlight the importance of NMDAR modulators in nociceptive signaling and in AD progression, we considered as important to investigate the effects of CR4056 on NMDAR activity. In primary culture of cortical neurons, application of NMDA and glycine elicits a current that is decreased in a dose-dependent fashion by CR4056 (IC50 5.3 ± 0.1 µM). CR4056 antagonism is reversible, not competitive and voltage-independent and it is not blocked by pertussis toxin. CR4056 interacts with the co-agonist glycine site in a competitive way, indeed high glycine concentrations diminish its effect. Fibroblasts expressing different recombinant NMDA receptors are differently modulated by CR4056: the potency and the efficacy of the compound are higher in GluN1- GluN2B than in GluN1-GluN2A containing receptors. In lamina II neurons of spinal cord slices, single stimulation of afferent fibers evokes an NMDA-mediated current that is inhibited by 10 µM CR4056. Repetitive stimulation of the dorsal root at high frequency and high intensity produces a firing activity that is significatively depressed by CR4056. Taken together, our results broad the understanding of the molecular mechanisms of CR4056 analgesic activity, involving the modulation of NMDAR activity. Therefore, we propose that the analgesic action of CR4056 and the neuroprotective effects in AD models may be mediated also by NMDAR inhibition.

The value of undenatured collagen for the normalization of the function of the cartilaginous tissue of the joints

Among the proteins of the human body, collagen accounts for at least 25–45% collagen; it is an essential structural component of skeletal tissues, connective tissue of internal organs (heart, intestines, lungs, liver, kidneys), as well as blood vessels. The variety of types of collagen is due to their role and function. The article presents information about the structure and synthesis of collagen, a high concentration of glycine, proline and hydroxyproline in the alpha chains of the collagen helix. Attention is drawn to the fact that cross-links and orientation of collagen fibers in the direction of the vector of external forces and loads provide protection to tissues and organs. The clinical significance of type II collagen is considered on the example of the cartilaginous tissue of the joints and tendons. It is emphasized that an imbalance in the structure of nutrition, genetic mutations, dysfunction of the endocrine and immune systems, especially in old age, are associated with the occurrence of one of the most common joint diseases – osteoarthritis (ОА). It has been established that the degradation or reduction of type II collagen in the cartilage matrix is accompanied by the progression of this disease. Due to the increasing prevalence of OA, signs of metabolic disorders and post-traumatic joint injuries, there is a growing interest in non-pharmacological and pharmacological interventions for the prevention and treatment of osteoarthritis. In recent years, convincing evidence has emerged of the successful use of drugs (biologically active food supplements) of collagen in osteoarthritis. The article presents the results of experimental and clinical studies, meta-analysis and systematic review, confirming the possibility of using these drugs (products) as part of the complex treatment of OA. The possibility of using compositions based on undenatured (native) collagen type II, with the inclusion of ascorbic acid, vitamin D, methylsulfonylmethane and boswellic acids promotes the synergy of these substances, slows down the rate of cartilage destruction, reduces the manifestation of pain and inflammation in the joints, improves functional joint and spinal conditions, promotes the synthesis of endogenous collagen.

Effect of glycine as a complex agent on the surface and corrosion properties of Ni-P and Ni-P/Al2O3 electroless coating

Purpose The ability to produce a uniform composition, high corrosion resistance with a hard coating layer during the electroless coating techniques are mainly based on the plating bath composition. The complexing agent is one of the most important components that control the coating layer properties. This paper aims to investigate the effect of the glycine as a complex agent on the surface and corrosion properties of Ni-P and Ni-P/Al2O3 electroless coating. Design/methodology/approach In this study, the effect of glycine as a complexing agent on the final surface and corrosion properties of the Ni-P and Ni-P/Al2O3 coatings has been investigated. The surface morphology and composition of the coated samples were investigated by scanning electron microscope (SEM) imaging and energy dispersive x-ray spectroscopy (EDS) analysis. Linear polarization scan and electrochemical impedance spectroscopy techniques were used to investigate the corrosion properties of the coating layer. Findings The results clarify that, glycine has a remarkable effect on the porosity content of Ni-P and Ni-P/Al2O3. It was found that increasing of glycine concentration results in higher porosity content in the coating layers. Also, the porosity in the coating layers minimizes the protectability of the coating against corrosion. The results also show that adding nano-alumina (Al2O3) to the coating path has improved the corrosion properties by decreasing the porosity in the coating layer. The scanning electron microscope (SEM) images showed that the concentration of glycine affects the content and distribution of alumina nanoparticles embedded in the coating layer. Also, it was observed that using a high concentration of glycine (0.4 M glycine), the alumina tends to agglomerate and the final alumina content in the coating was decreased. Originality/value The present study reveals that the quality of the final coating plays a major role in the corrosion performance of the steel substrate. The coating quality can by improve remarkably by optimization of the complexing agent used in the plating bath, to minimize the porosity involve in the coating layer.

Nucleation kinetics of glycine promoted concentrated potassium carbonate solvents for carbon dioxide absorption

Glycine promoted concentrated potassium carbonate (K2CO3) solvents are considered to have potential for use in carbon dioxide (CO2) capture processes. Understanding their precipitation behaviour, particularly nucleation kinetics, becomes important if the solvents are used as absorbents at concentrations of 40 wt% or greater. In this work, liquid-solid equilibrium of the quaternary solvent system glycine-potassium carbonate-potassium bicarbonate-water was investigated in an Optimax workstation 1001 at different temperatures. The results were interpreted using a regressed Electrolyte Non Random Two Liquids (ENRTL) thermodynamic model in Aspen PlusTM within an average deviation of 9.2%. Through X-ray diffraction (XRD), scanning electron microscopy (SEM), high performance liquid chromatography (HPLC) and total nitrogen elemental analysis, the precipitates confirmed that only kalicinite (KHCO3), and no glycine related products such as glycine solids and carbamates precipitated under the temperatures investigated. The metastable zone width (MSZW) of the solvent systems with different concentrations of glycine at different constant cooling rates was measured using focused beam reflectance measurement (FBRM), and four methods including Nývlt relation, Self-Nývlt relation, the CNT theory and the pseudo induction time method were used to evaluate nucleation kinetics. It was found that the introduction of glycine significantly increases the MSZW, resulting in fast nucleation kinetics. However, at a high concentration of glycine (1.36 mol/kg water) promoted 40 wt% K2CO3 with 0.4 CO2 loading, the maximum MSZW was achieved at an intermediate cooling rate (35 °C/h) rather than the highest cooling rate (60 °C/h), this may result from dual competing effects between strong ionic strength within the solvent system and superstation generated by cooling rates. Correspondingly, these traditional nucleation analysis methods cannot explain the nucleation kinetic behaviour for this specific case, and other theories are required to explain the obscured behaviour of the quaternary solvent system.

Why does hyperglycinemia exhibit so grave brain anomalies and so severe neurological symptoms?

Nonketotic-hyperglycinemia (NKH) is an autosomal recessive disorder associated with grave brain malformations and severe neurological symptoms, and also characterized by accumulation of a large amount of glycine in body fluids. NKH is caused by an inherited deficiency of the glycine cleavage system (GCS), which is the main system to degrade glycine in mammalians. These severe symptoms and grave bran malformations are not normally observed in the other amino acid metabolic disorders, suggesting that GCS should have unknown pivotal roles in brain development and function. Interestingly, GCS is indispensable in supplying proliferating cells with 5,10-methylenetetrahydrofolate as a one-carbon donor, which is essential for the synthesis of DNA in cell proliferation. Since GCS is expressed intensely and ubiquitously in the neuroepithelium, the lack of GCS might greatly impair the proliferation of neural stem cells. On the other hand, this system is also very important to regulate extracellular glycine concentrations. Since glycine is an important neurotransmitter, which binds to both glycine receptors and NMDA receptors, high glycine concentrations caused by the deficiency of GCS might cause the aberrant neurotransmission in the patient brains. Considering these unique two faces of GCS functions, proliferation disturbance and aberrant neurotransmission are intricately mixed in the developing brain, leading to the grave brain malformations and sever neurological symptoms.

High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis

Collagen synthesis is severely diminished in osteoarthritis; thus, enhancing it may help the regeneration of cartilage. This requires large amounts of glycine, proline and lysine. Previous works of our group have shown that glycine is an essential amino acid, which must be present in the diet in large amounts to satisfy the demands for collagen synthesis. Other authors have shown that proline is conditionally essential. In this work we studied the effect of these amino acids on type II collagen synthesis. Bovine articular chondrocytes were cultured under a wide range of different concentrations of glycine, proline and lysine. Chondrocytes were characterized by type II collagen immunocytochemistry of confluence monolayer cultures. Cell growth and viability were assayed by trypan blue dye exclusion method. Type II collagen was measured in the monolayer, every 48 h for 15 days by ELISA. Increase in concentrations of proline and lysine in the culture medium enhances the synthesis of type II collagen at low concentrations, but these effects decay before 1.0 mM. Increase of glycine as of 1.0 mM exceeds these effects and this increase continues more persistently by 60–75%. Since the large effects produced by proline and lysine are within the physiological range, while the effect of glycine corresponds to a much higher range, these results demonstrated a severe glycine deficiency for collagen synthesis. Thus, increasing glycine in the diet may well be a strategy for helping cartilage regeneration by enhancing collagen synthesis, which could contribute to the treatment and prevention of osteoarthritis.

Modulation of GABA and glycine receptors in rat pyramidal hippocampal neurones by 3α5β-pregnanolone derivatives

The ability of pregnanolone glutamate (PA-Glu), pregnanolone hemisuccinate (PA-hSuc) and pregnanolone hemipimelate (PA-hPim), neuroactive steroids with a negative modulatory effect on excitatory N-methyl-d-aspartate receptors, to influence the functional activity of inhibitory γ-aminobutyric acid and glycine receptors was estimated. The GABA- and glycine-induced chloride currents (IGABA and IGly) were measured in isolated pyramidal neurons of the rat hippocampus using the patch-clamp technique. Compound PA-Glu was found to potentiate IGABA and to inhibit IGly, while PA-hSuc and PA-hPim inhibited both IGABA and IGly. Moreover, PA-Glu, PA-hSuc, and PA-hPim had a greater effect on desensitization than on the peak amplitude of IGly. At a high concentration of glycine (500 μM), the effect of neurosteroids on the peak amplitude of IGly disappeared, and the acceleration of desensitization remained. The conversion of PA-Glu into androstane glutamate (AND-Glu), an analogue that lacks the C-17 acetyl moiety, completely eliminated the effects on these receptors. Our results indicate that the C-17 acetyl moiety is crucial for the action on IGABA and IGly. Our results indicate that the pregnanolone derivatives, in contrast to the androstane analogues, modulate IGABA and IGly at low micromolar concentrations and this family of neurosteroids can be useful for future structure-activity relationship studies of the steroid modulation of other receptor types.

A Glycine Riboswitch in Streptococcus pyogenes Controls Expression of a Sodium:Alanine Symporter Family Protein Gene.

Regulatory RNAs play important roles in the control of bacterial gene expression. In this study, we investigated gene expression regulation by a putative glycine riboswitch located in the 5′-untranslated region of a sodium:alanine symporter family (SAF) protein gene in the group A Streptococcus pyogenes serotype M49 strain 591. Glycine-dependent gene expression mediated by riboswitch activity was studied using a luciferase reporter gene system. Maximal reporter gene expression was observed in the absence of glycine and in the presence of low glycine concentrations. Differences in glycine-dependent gene expression were not based on differential promoter activity. Expression of the SAF protein gene and the downstream putative cation efflux protein gene was investigated in wild-type bacteria by RT-qPCR transcript analyses. During growth in the presence of glycine (≥1 mM), expression of the genes were downregulated. Northern blot analyses revealed premature transcription termination in the presence of high glycine concentrations. Growth in the presence of 0.1 mM glycine led to the production of a full-length transcript. Furthermore, stability of the SAF protein gene transcript was drastically reduced in the presence of glycine. We conclude that the putative glycine riboswitch in S. pyogenes serotype M49 strain 591 represses expression of the SAF protein gene and the downstream putative cation efflux protein gene in the presence of high glycine concentrations. Sequence and secondary structure comparisons indicated that the streptococcal riboswitch belongs to the class of tandem aptamer glycine riboswitches.

Effects of Dietary Supplementation with Fish Scales-Derived Collagen Peptides on Skin Parameters and Condition: A Randomized, Placebo-Controlled, Double-Blind Study

Fish scales-derived collagen peptides (CPs) are characterized by their specific amino acid composition with a high concentration of glycine, proline and hydroxyproline. These amino acids have been known to exert beneficial effects on human skin. The aim of the present study was to examine the effects of collagen peptides obtained from fish scales on changes in periorbital wrinkles, facial skin hydration, and skin elasticity in healthy women aged 30–60 years. In the present randomized, placebo-controlled, double-blind trial, 71 subjects consumed a 20 mL beverage containing 3000 mg of CPs or placebo once per day over 12 weeks. Significant decreases in periorbital wrinkles (p < 0.05) were observed in the treatment group after 12 weeks of CPs ingestion compared to the control group. This study also demonstrated a consistent trend of enhanced facial skin moisture (p < 0.001) and skin elasticity (p < 0.001) by dietary intake of CPs without any side effects or adverse events. These findings indicate that fish-derived CPs hold great promise as a natural supplement with cutaneous anti-aging properties.