Search

This study investigates the effects of kinetic energy and projectile size on particle emission from a phenylalanine overlayer adsorbed on a graphene bilayer during argon projectile bombardment. Projectiles of various sizes (1–1000 atoms) and kinetic energies (0.5–40 keV) are used to study their impact on the ejection efficiency, mass distribution, and kinetic and angular spectra of the emitted substances. Particle ejection mechanisms are discussed in scenarios with and without sample perforation. Additionally, this study investigated the potential use of graphene in secondary ion mass spectrometry or neutral secondary mass spectrometry analyses. [ABSTRACT FROM AUTHOR]

A new series of phenylalanine‐derived carboxamides with sulfonamide functionality is designed, synthesized, and assessed for their in silico studies, in vitro antimalarial, and antioxidant activities. The interaction of 4‐nitrobenzene sulfonyl chloride with phenylalanine in a basic aqueous solution yielded an intermediate ((4‐nitrophenyl)sulfonyl)phenylalanine. The reaction of various cyclic amines with the intermediate, utilizing phenylboronic acid as the coupling agent, yielded the carboxamides derivatives. The derived‐carboxamides passed in silico test and fulfilled all the allowed ranges for molecular descriptors. Optimization was achieved before compounds were deployed as ligands in molecular docking studies using density functional theory utilizing the functional B3LYP and the basis set 6–31G**. The docking experiments were done on the active site of FKBP35 binding domain of Plasmodium falciparum for antimalarial impact whereas that of antioxidants was performed on the active site of PDB ID:IXAN. The computational antimalarial and antioxidant study demonstrated that the compounds displayed a high binding affinity with the target protein residues via hydrogen bonding, π‐π, π‐alkyl, π‐sigma, and π‐cation bonding interactions. Additionally, the new compounds were evaluated for in vitro antimalarial and antioxidant properties. The screening findings suggest that the new compounds exhibit effective antimalarial and antioxidant action compared to traditional medicines. [ABSTRACT FROM AUTHOR]

The kidney is considered the main site for the net release of Tyrosine (Tyr) to the circulation through hydroxylation of Phenylalanine (Phe) using phenylalanine hydroxylase enzyme. In chronic kidney disease (CKD) patients the enzyme activity is impaired, therefore the serum concentration ratio of Tyr/Phe is reduced compared to healthy individuals. This motivates us to develop a cost effective, green, simple, sensitive, and selective HPTLC method to measure the levels of Tyr and Phe in serum samples. The analysis was carried out using acetonitrile: ethanol: 25% ammonia solution: ethyl acetate (6.5: 1.5: 1: 0.5) as a mobile phase. Rf values were 0.55 ± 0.05 for Phe and 0.39 ± 0.05 for Tyr. Densitometry scanning was performed using UV detector and dual wavelengths of 210 and 225 nm were obtained. A linear correlation was observed between the levels of Phe and Tyr, ranging from 50 to 700 ng band− 1 and 50 to 600 ng band− 1, respectively, under the optimum conditions. The method selectivity, linearity, precision, accuracy, and robustness were all confirmed in accordance with ICH recommendations. Calculations of the separation and resolution factors, number of theoretical plates, and height equivalent to theoretical plates prove to the chromatographic system accuracy and high separation efficiency. The developed method exhibits an acceptable eco-scale when measuring the method greenness using AGREE and GAPI softwares. It was applied for the determination of Phe and Tyr concentrations in human serum samples. [ABSTRACT FROM AUTHOR]

Polyamides (PAs) with aspartame‐derived diketopiperazine (DKP) form specific particles and exhibit high heat resistance. In this study, we investigated the stereostructures of aspartic acid and phenylalanine, which constitute aspartame DKP. Diketopiperazines with different stereostructures were synthesized from D‐ and L‐aspartic acid and D‐ and L‐phenylalanine, and LL‐, DD‐, and LD‐type aminodiketopiperazines (LL, DD, and LD‐ADKPs) were obtained. These ADKPs differed in their crystal forms depending on their stereoisomeric structures. Furthermore, PAs were formed from these ADKPs via polycondensation using triphenyl phosphite/pyridine, and their heat resistance was approximately 300 °C. The secondary structure of each PA was evaluated by circular dichroism, which suggested that LD‐type PAs had a mixed secondary structure of coils and helical structures, unlike the LL and DD types. Precipitated LL, DD, and LLcoDD PAs formed similar particles, whereas the particles of the large LD‐type PA had different particle shapes owing to their different conformations. [ABSTRACT FROM AUTHOR]

We employed an untargeted proteo‐metabolomic approach to profile circulating biomarkers in plasma samples from the I‐Lan Longitudinal Aging Study, aiming to identify biomarkers and pathways associated with physio‐cognitive decline syndrome (PCDS). In 115 propensity score‐matched PCDS case–control pairs, pathway analyses implicated dysregulation of fatty acid metabolism and inflammation in PCDS pathogenesis. Sex‐specific associations were observed, with disruptions in central carbon metabolism (elevated PKM, MDH1, and GAPDH; decreased MINPP1) and tyrosine metabolism (decreased MIF, DBH; increased thyroxine) characterizing in men. In contrast, perturbations in glutathione and phenylalanine metabolism, including increased ANPEP, GSTP1, and decreased pyroglutamic acid, were identified in women. Results suggest that dysregulated energy and redox homeostasis likely contribute to PCDS development. Notably, ANPEP, PKM, and MIF emerged as potential biomarkers, elucidating the muscle–brain crosstalk framework. Our findings provide insights into potential molecular mechanisms underlying PCDS and the muscle–brain crosstalk, marking progress toward elucidating biomarkers in the journey of healthy aging. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion The long‐term prognosis of treated phenylketonuria (PKU) is a controversial issue. A controlled long‐term study was performed to assess the neuropsychological outcome in adult patients with early treated PKU.We investigated 27 patients aged 34–55 years (median age: 47 years) and 19 healthy controls, matched for age and socio‐economic status. Patients and controls were assessed for their full‐scale IQ (FSIQ), attention and information‐processing abilities. Magnetic resonance imaging (MRI) of the brain was performed in all patients. Neuropsychological assessments and MRI were repeated at a 15‐year follow‐up.In the entire interval of 15 years, cognitive performance of patients and controls remained unchanged. Older adult patients showed poorer cognitive performance at all assessment times compared to young adult patients and controls. Cognitive performance showed no correlation to MRI results. FSIQ, however, was significantly correlated with blood phenylalanine levels in the adolescent years of adult patients older than 47 years.Cognitive performance in adult patients with early treated PKU does not seem to deteriorate in a 15 years interval. Neuropsychological assessment revealed constant modest neurocognitive impairment in patients older than 47 years. This seems to refer to an early relaxation of diet that was recommended when the older patients were adolescents. [ABSTRACT FROM AUTHOR]

Chiral phenylalanine derivatives are important raw materials and building blocks for the synthesis of peptides and drug molecules. Enantiomerically pure D/L‐3‐pyridyl‐ and phenylalanine has shown wide application potential in the synthesis of various drug intermediates. This article focuses on two synthetic routes from different feedstocks. The first approach is an Erlenmeyer–Plöchl route study using N‐acetylglycine as starting material, whereas the second is an alkylation route study using diethyl acetamidomalonate as starting material. The key step is the resolution of N‐acetamido‐alanine esters using different quantities of fairly inexpensive Protamex proteinase to obtain pure enantiomeric D/L‐3‐pyridyl‐ and substituted phenylalanine or its derivative, with the ee value and purity of all products exceeding 99%. The different chiral arylalanine derivatives that can be prepared using the above two methods have good versatility. [ABSTRACT FROM AUTHOR]

Context: The human body contains many different types of transition metal ions, such as Zn2+, Cu2+, which are involved in many physiological processes. An excess or deficiency of these ions can cause diseases, such as Alzheimer's disease, which is closely related to the levels of these ions in the body. In-depth understanding of various physiological and pathological mechanisms related to metal ions requires understanding the interaction between metal ions and nearby amino acids at the atomic level. This article selected four transition metal ions: Zn2+, Cu2+, Fe2+, and Mn2+ and the aromatic amino acid Phe, known for its strong coordination capability, as study subjects, comprehensively examining their binding situations. The results show that there are multiple binding modes between them and Phe, and most of the binding modes involve benzene ring coordination. The coordination strength order of the four metal ions with benzene ring, carbonyl O, hydroxyl O and amino N is different. For the lowest energy structure formed by each ion with Phe, all four ions are bound to N, carbonyl O, and benzene ring. Zn2+ is combined with two C's of the benzene ring, Cu2+ with four C's of the benzene ring, and Fe2+ and Mn2+ with the benzene ring as a whole. Part of the reason for this phenomenon may be derived from the tendency of transition metal ions to reach 18e stable structures when bound to ligands. There is a strong binding force between the four ions and Phe, and the binding trend is Cu2+(-294.9 kcal/mol) > Zn2+(-261.3 kcal/mol) > Fe2+(-247.5 kcal/mol) > Mn2+(-220.2 kcal/mol). Mayer bond order analysis and molecular orbital localization analysis found that there are very strong chemical interactions between transition metal ions and surrounding atoms, especially with N and carbonyl O. Methods: Several initial structures with different coordination modes to Phe were created according to chemical intuition for each divalent cation. Then semiempirical MD simulations at GFN2 level were run on these structures. The numerous generated structures were classified according to some criteria, then representative geometries were preliminarily optimized by TPSSh/6-31G*/LanL2DZ. To get more accurate electronic energies, high-precision quantum chemistry calculations at the level of TPSSh/def2TZVPP//TPSSh/def2QZVPP were carried out on the selected low-lying structures. All the optimized structures were confirmed to be minima without imaginary frequency by performing frequency analyses. Further electronic structure analyses such as IRI, Mayer bond order, IBSI etc. were performed to get more insights into the binding between the transition metal ions and Phe. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the effects of dietary supplementation of arginine (ARG) or guanidinoacetic acid (GAA), with or without phenylalanine (PHE), on the ascites susceptibility in the cold‐stressed broilers fed canola meal (CM)‐based diet. Method: A total of 450 one‐day‐old male broiler chicks were randomly allocated to 30 floor pens with 6 replications for each of the 5 treatments. The dietary treatments were as follows: CM‐based diet (control), CM‐based diet + 2.57 g/kg ARG, CM‐based diet + 1.8 g/kg GAA, CM‐based diet + 2.57 g/kg ARG + 1.5 g/kg PHE and CM‐based diet + 1.8 g/kg GAA + 1.5 g/kg PHE. The groups experienced cold stress induction starting at 32°C on day one, with gradual reductions to 15°C on days 21. The temperature was then held at 15°C for the remainder of the experiment. Results: The supplements ARG + PHE and GAA + PHE resulted in improved feed conversion ratios (FCR) when compared to the control group. In comparison with the control group, supplementation of ARG and ARG + PHE decreased the ascites mortality by increasing the plasma nitric oxide level (NO), blood O2 partial pressure, blood O2 saturation (SO2), and decreasing the blood CO2 partial pressure (PCO2) and right ventricle to total ventricle (RV:TV) ratio. Supplementation of GAA and GAA + PHE also declined ascites mortality by reducing blood PCO2 while increasing blood SO2 and plasma NO levels. Although plasma corticosterone level and RV:TV ratio were similar between the GAA and control groups, adding GAA + PHE significantly reduced both compared to the control group. Conclusion: In summary, supplementing cold‐stressed broiler chicken diets with 2.57 g/kg ARG may alleviate hypertension. Additionally, 1.8 g/kg GAA proves to be an effective substitute for dietary ARG in low‐ARG diets, alleviating adverse effects from cold stress. Proper PHE formulation, at 1.5 g/kg in this study, is crucial when using ARG and GAA supplements. [ABSTRACT FROM AUTHOR]

Phenylketonuria is a rare metabolic disease resulting from a deficiency of the enzyme phenylalanine hydroxylase. Recent cross-sectional evidence suggests that early-treated adults with phenylketonuria exhibit alterations in cortical grey matter compared to healthy peers. However, the effects of high phenylalanine exposure on brain structure in adulthood need to be further elucidated. In this double-blind, randomized, placebo-controlled crossover trial, we investigated the impact of a 4-week high phenylalanine exposure on the brain structure and its relationship to cognitive performance and metabolic parameters in early-treated adults with phenylketonuria. Twenty-eight adult patients with early-treated classical phenylketonuria (19–48 years) underwent magnetic resonance imaging before and after the 4-week phenylalanine and placebo interventions (four time points). Structural T1-weighted images were preprocessed and evaluated using Direct Cortical Thickness Estimation using Deep Learning-based Anatomy Segmentation and Cortex Parcellation (DL+DiReCT), a deep-learning-based tool for brain morphometric analysis. Cortical thickness, white matter volume and ventricular volume were compared between the phenylalanine and placebo periods. Brain phenylalanine levels were measured using 1H spectroscopy. Blood levels of phenylalanine, tyrosine, and tryptophan were assessed at each of the four time points, along with performance in executive functions and attention. Blood phenylalanine levels were significantly higher after the phenylalanine period (1441 µmol/l) than after the placebo period (873 µmol/l, P < 0.001). Morphometric analyses revealed a statistically significant decrease in cortical thickness in 17 of 60 brain regions after the phenylalanine period compared to placebo. The largest decreases were observed in the right pars orbitalis (point estimate = −0.095 mm, P < 0.001) and the left lingual gyrus (point estimate = −0.070 mm, P < 0.001). Bilateral white matter and ventricular volumes were significantly increased after the phenylalanine period. However, the structural alterations in the phenylalanine-placebo group returned to baseline measures following the washout and placebo period. Additionally, elevated blood and brain phenylalanine levels were related to increased bilateral white matter volume (rs = 0.43 to 0.51, P ≤ 0.036) and decreased cortical thickness [ rs = −0.62 to −0.39, not surviving false discovery rate (FDR) correction] after the phenylalanine and placebo periods. Moreover, decreased cortical thickness was correlated with worse cognitive performance after both periods (rs = −0.54 to −0.40, not surviving FDR correction). These findings provide evidence that a 4-week high phenylalanine exposure in adults with phenylketonuria results in transient reductions of the cortical grey matter and increases in white matter volume. Further research is needed to determine the potential long-term impact of high phenylalanine levels on brain structure and function in adults with phenylketonuria. [ABSTRACT FROM AUTHOR]

Background: The unfolded protein response (UPR) is a proteostatic process that is activated in response to endoplasmic reticulum stress. It is currently unclear how aging influences the chronic and adaptive UPR in human skeletal muscle. Here we determined the effect of aging on UPR activation at rest, in response to exercise, and the associations with muscle function. Methods: Thirty young (20-35 yr) and 50 older (65-85 yr) individuals were enrolled. Vastus lateralis biopsies were performed at rest and 3 and 48 h after a single bout of resistance exercise. The abundance of UPR-related transcripts and proteins was measured by RNA sequencing and Western blotting, respectively. Fractional synthetic rates of muscle protein were determined by mass spectrometry after intravenous infusion of 13C6 phenylalanine. Results: Older adults demonstrated elevated transcriptional and proteomic markers of UPR activation in resting muscle. Resting UPR gene expression was negatively associated with muscle strength and power in older adults. The UPR is similarly activated by acute resistance exercise in young and older adults and positively associated with muscle function but not the anabolic response to exercise. Conclusions: Skeletal muscle from older adults exhibits chronically activated UPR, which accompanies functional decline. The adaptive UPR is a proteostatic mechanism that is upregulated in response to exercise in young and older adults and positively associated with muscle function. [ABSTRACT FROM AUTHOR]

Cordyceps chanhua , an important cordycipitoid medical mushroom with wide use in Asia, has gained attention for its bioactive component beauvericin (BEA), which is of medicinal value as a drug lead, but also of food safety risk. Recent observations by our group revealed a significant decrease of BEA content in C. chanhua when exposed to light, but the underlying regulatory mechanisms remain elusive. In this study, a comprehensive approach combining metabolomics and transcriptomics was employed to investigate the effects of white light on the secondary metabolism of C. chanhua for elucidation of the influence of light on BEA biosynthesis in this fungus. The result showed that the genes and metabolites involved in the synthesis of D-hydroxyisovaleric acid, a precursor of BEA synthesis, were down-regulated under light exposure, while those associated with the synthesis of phenylalanine, another precursor of BEA synthesis, were up-regulated leading to elevated phenylalanine levels. It suggested that the suppressive effect of light on BEA synthesis in C. chanhua occurred primarily through the inhibition of D-hydroxyisovaleric acid synthesis, while the enhanced phenylalanine biosynthesis likely directed towards other metabolic pathway such as pigment synthesis. These results contributed to a better understanding on how light modulates the secondary metabolism of C. chanhua and provided valuable guidance for optimizing BEA production in cultivation practices. [Display omitted] • Light inhibits the production of beauvericin (BEA) in Cordyceps chanhua. • Light reduces BEA by suppressing D-hydroxyisovaleric acid, a precursor. • Light boosts phenylalanine, another precursor, but changes its metabolic path. • Light exposure induces oxidative stress and stimulates the consumption of BEA. [ABSTRACT FROM AUTHOR]

The identification of new genes involved in regulating cold tolerance in rice is urgent because low temperatures repress plant growth and reduce yields. Cold tolerance is controlled by multiple loci and involves a complex regulatory network. Here, we show that rice jacalin‐related lectin (OsJRL) modulates cold tolerance in rice. The loss of OsJRL gene functions increased phenylalanine metabolism and flavonoid biosynthesis under cold stress. The OsJRL knock‐out (KO) lines had higher phenylalanine ammonia‐lyase (PAL) activity and greater flavonoid accumulation than the wild‐type rice, Nipponbare (NIP), under cold stress. The leaves had lower levels of reactive oxygen species (ROS) and showed significantly enhanced cold tolerance compared to NIP. In contrast, the OsJRL overexpression (OE) lines had higher levels of ROS accumulation and showed lower cold tolerance than NIP. Additionally, the OsJRL KO lines accumulated more abscisic acid (ABA) and jasmonic acid (JA) under cold stress than NIP. The OsJRL OE lines showed increased sensitivity to ABA compared to NIP. We conclude that OsJRL negatively regulates the cold tolerance of rice via modulation of phenylalanine metabolism and flavonoid biosynthesis. Summary statement: OsJRL negatively regulates the cold tolerance of rice via modulation of phenylalanine metabolism and flavonoid biosynthesis. [ABSTRACT FROM AUTHOR]

Salt stress severely inhibits crop growth and production. The native turfgrass species Carex rigescens in northern China, exhibits extraordinary tolerance to multiple abiotic stresses. However, little is known about its specific metabolites and pathways under salt stress. To explore the molecular metabolic mechanisms under salt stress, we conducted metabolome analysis combined with transcriptome analysis of two varieties of Carex rigescens with differing salt tolerances: salt-sensitive Lvping NO.1 and salt-tolerant Lvping NO.2. After 5 days of salt treatment, 114 and 131 differentially abundant metabolites (DAMs) were found in Lvping NO.1 and Lvping NO.2, respectively. Among them, six amino acids involved in the amino acid biosynthesis pathway, namely, valine, phenylalanine, isoleucine, tryptophan, threonine, and serine, were accumulated after treatment. Furthermore, most DAMs related to phenylalanine biosynthesis, metabolism, and phenylpropanoid biosynthesis increased under salt stress in both varieties. The expression profiles of metabolism-associated genes were consistent with the metabolic profiles. However, genes including HCT, β-glucosidases, and F5H, and metabolite 4-hydroxycinnamic acid, of the two varieties may account for the differences in salt tolerance. Our study provides new insights into the mechanisms underlying salt tolerance in Carex rigescens and reveals potential metabolites and genes to improve crop resilience to saline environments. [ABSTRACT FROM AUTHOR]

Aroma plays a pivotal role in defining tea quality and distinctiveness, and tea producers have often observed that specific drought conditions are closely associated with the formation and accumulation of characteristic aroma compounds in tea leaves. However, there is still limited understanding of the differential strategies employed by various tea cultivars in response to drought stress for the accumulation of key volatile aroma compounds in fresh tea leaves, as well as the associated metabolic pathways involved in aroma formation. In this study, two widely cultivated tea cultivars in China, Fuding Dabai (FD) and Wuniuzao (WNZ), were examined to assess the impact of mild field drought stress on the composition and accumulation of key volatile aroma compounds in fresh leaves using headspace gas chromatography–ion mobility spectrometry (HS-GC-IMS) and headspace solid phase micro-extraction gas chromatography–mass spectrometry (HS-SPME-GC-MS) technologies. Results revealed that drought stress led to a substantial increase in the diversity of volatile compounds (VOCs) in FD, while WNZ exhibited a notable rise in low-threshold VOC concentrations, amplifying sweet, floral, fruity, and earthy aroma profiles in post-drought fresh leaves. Through partial least squares discriminant analysis (PLS-DA) of HS-GC-IMS and HS-SPME-GC-MS data, integrating variable importance projection (VIP) scores and odor activity values (OAVs) above 1, 9, and 13, key odor-active compounds were identified as potential markers distinguishing the drought responses in the two cultivars. These compounds serve as crucial indicators of the aromatic profile shifts induced by drought, providing insights into the differential metabolic strategies of the cultivars. Additionally, KEGG enrichment analysis revealed 12 metabolic pathways, such as terpenoid biosynthesis, fatty acid synthesis, cutin, suberine, and wax biosynthesis, and phenylalanine metabolism, which may play crucial roles in the formation and accumulation of VOCs in tea leaves under drought stress. These findings provide a comprehensive framework for understanding the cultivar-specific mechanisms of aroma formation and accumulation in tea leaves under mild drought conditions. [ABSTRACT FROM AUTHOR]

Polylactide (PLA), a biocompatible and biodegradable polymer, is widely used in diverse biomedical applications. However, the industry standard for converting lactide into PLA involves toxic tin (Sn)‐based catalysts. To mitigate the use of these harmful catalysts, other environmentally benign metal‐containing agents for efficient lactide polymerization have been studied, but these alternatives are hindered by complex synthesis processes, reactivity issues, and selectivity limitations. To overcome these shortcomings, we explored the catalytic activity of Cu‐(Phe)2 and Zn‐(Phe)2 metal‐amino acid co‐assemblies as potential catalysts of the ring‐opening polymerization (ROP) of lactide into PLA. Catalytic activity of the assemblies was monitored at different temperatures and solvents using 1H‐NMR spectroscopy to determine the catalytic parameters. Notably, Zn‐(Phe)2 achieved >99% conversion of lactide to PLA within 12 h in toluene under reflux conditions and was found to have first‐order kinetics, whereas Cu‐(Phe)2 exhibited significantly lower catalytic activity. Following Zn‐(Phe)2‐mediated catalysis, the resulting PLA had an average molecular weight of 128 kDa and a dispersity index of 1.25 as determined by gel permeation chromatography. Taken together, our minimalistic approach expands the realm of metal‐amino acid‐based supramolecular catalytic nanomaterials useful in the ROP of lactide. This advancement shows promise for the future design of simplified biocatalysts in both industrial and biomedical applications. [ABSTRACT FROM AUTHOR]

SUMMARY Plants direct substantial amounts of carbon toward the biosynthesis of aromatic amino acids (AAAs), particularly phenylalanine to produce lignin and other phenylpropanoids. Yet, we have a limited understanding of how plants regulate AAA metabolism, partially because of a scarcity of robust analytical methods. Here, we established a simplified workflow for simultaneous quantification of AAAs and their pathway intermediates from plant tissues, based on extraction at two alternative pH and analysis by Zwitterionic hydrophilic interaction liquid chromatography coupled to mass spectrometry. This workflow was then used to analyze metabolic responses to elevated or reduced carbon flow through the shikimate pathway in plants. Increased flow upon expression of a feedback‐insensitive isoform of the first shikimate pathway enzyme elevated all AAAs and pathway intermediates, especially arogenate, the last common precursor within the post‐chorismate pathway of tyrosine and phenylalanine biosynthesis. Additional overexpression of an arogenate dehydrogenase enzyme increased tyrosine levels and depleted phenylalanine and arogenate pools; however, the upstream shikimate pathway intermediates remained accumulated at high levels. Glyphosate treatment, which restricts carbon flow through the shikimate pathway by inhibiting its penultimate step, led to a predictable accumulation of shikimate and other precursors upstream of its target enzyme but also caused an unexpected accumulation of downstream metabolites, including arogenate. These findings highlight that the shikimate pathway and the downstream post‐chorismate AAA pathways function as independently regulated modules in plants. The method developed here paves the way for a deeper understanding of the shikimate and AAA biosynthetic pathways in plants. [ABSTRACT FROM AUTHOR]

Background: Obesity is one of the public health issues that seriously threatens human health. This study aimed to investigate the effects of wheat bran oil (WBO) on body weight and fat/lipid accumulation in high-fat diet (HFD)-induced obese rats and further explore the possible mechanisms by microbiome and metabolome analyses. Methods: Fifty Sprague-Dawley (SD) rats were fed either a normal chow diet (B group, n = 10) or HFD (n = 40) for 14 weeks to establish an obesity model. The HFD-induced obese rats were further divided into four groups and given WBO at 0 mL/kg (M group), 1.25 mL/kg (WBO-L group), 2.5 mL/kg (WBO-M group), and 5 mL/kg (WBO-H group) by oral gavage for 9 weeks. The body weight of rats was weighed weekly. The gut microbiota structure was analyzed using 16 S rDNA high-throughput sequencing. The liver metabolite profile was determined using UHPLC-QE-MS non-target metabolomics technology. Results: In this study, WBO treatment reduced body weight gain, fat and lipid accumulation, and ameliorated hepatic steatosis and inflammation. WBO treatment increased the relative abundance of Romboutsia and Allobaculum and decreased that of Candidatus_Saccharimonas, Alloprevotella, Rikenellaceae_RC9_gut_group, Alistipes, Parabacteroides, UCG-005, Helicobacter, Colidextribacter, and Parasutterella compared with the M group. A total of 22 liver metabolites were significantly altered by WBO treatment, which were mainly involved in taurine and hypotaurine metabolism, nicotinate and nicotunamide metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and ether lipid metabolism. Conclusions: WBO alleviated body weight gain and fat/lipid accumulation in HFD-induced obese rats, which may be related to altered gut microbiota and liver metabolites. [ABSTRACT FROM AUTHOR]

Summary In plants, L‐serine (Ser) biosynthesis occurs through various pathways and is highly dependent on the atmospheric CO2 concentration, especially in C3 species, due to the association of the Glycolate Pathway of Ser Biosynthesis (GPSB) with photorespiration. Characterization of a second plant Ser pathway, the Phosphorylated Pathway of Ser Biosynthesis (PPSB), revealed that it is at the crossroads of carbon, nitrogen, and sulphur metabolism. The PPSB comprises three sequential reactions catalysed by 3‐phosphoglycerate dehydrogenase (PGDH), 3‐phosphoSer aminotransferase (PSAT) and 3‐phosphoSer phosphatase (PSP). PPSB was overexpressed in plants exhibiting two different modes of photosynthesis: Arabidopsis (C3 metabolism), and maize (C4 metabolism), under ambient (aCO2) and elevated (eCO2) CO2 growth conditions. Overexpression in Arabidopsis of the PGDH1 gene alone or PGDH1, PSAT1 and PSP1 in combination increased the Ser levels but also the essential amino acids threonine (aCO2), isoleucine, leucine, lysine, phenylalanine, threonine and methionine (eCO2) compared to the wild‐type. These increases translated into higher protein levels. Likewise, starch levels were also increased in the PPSB‐overexpressing lines. In maize, PPSB‐deficient lines were obtained by targeting PSP1 using Cas9 endonuclease. We concluded that the expression of PPSB in maize male gametophyte is required for viable pollen development. Maize lines overexpressing the AtPGDH1 gene only displayed higher protein levels but not starch at both aCO2 and eCO2 conditions, this translated into a significant rise in the nitrogen/carbon ratio. These results suggest that metabolic engineering of PPSB in crops could enhance nitrogen content, particularly under upcoming eCO2 conditions where the activity of GPSB is limited. [ABSTRACT FROM AUTHOR]

Background: Encephalitis associated with antibodies against the N-methyl-Daspartate receptor (NMDAR) results in a distinctive neuro-psychiatric syndrome. It has been reported that the serum phenylalanine-tyrosine (Phe/Tyr) ratio increases during infection. However, the connection between phenylalaninetyrosine metabolism and psychiatric symptoms remains unclear. Methods: We enrolled 24 individuals with anti-NMDAR encephalitis and 18 individuals with non-inflammatory neurological diseases (OND). Chromatography was used to measure serum levels of phenylalanine and tyrosine. Serum and cerebrospinal fluid (CSF) TNF-a levels were obtained from the clinical database. The modified Rankin Scale (mRS) score and Glasgow Coma Scale (GCS) score were recorded during the acute phase. The area under the curve (AUC) of the receiver operating characteristic curve was used to assess prediction efficacy. Results: In NMDAR patients, levels of serum Phe and the ratio of serum Phe/Tyr were higher compared to OND patients. The serum Phe/Tyr ratio was also elevated in NMDAR patients with psychiatric syndrome. Furthermore, serum Phe and Tyr levels were correlated with inflammatory indexes. Conclusion: The serum Phe/Tyr ratio is elevated in NMDAR patients with psychiatric syndrome and is associated with severity. Therefore, the serum Phe/Tyr ratio may serve as a potential prognostic biomarker. [ABSTRACT FROM AUTHOR]

To investigate the differences in serum tryptophan, lysine, and phenylalanine levels in breast cancer patients, the correlation between the three amino acids with the chemotherapy regimen, and their significance in the clinical diagnosis and treatment of breast cancer. Clinical data were collected from the Department of Breast Surgery at Yunnan Cancer Hospital, encompassing 216 cases from July to December 2020, including 91 healthy individuals, 38 with benign tumors, and 87 with cancer. Amino acid levels were measured using liquid chromatography-tandem mass spectrometry. Statistical analyses, such as the Kruskal-Wallis H-test and Wilcoxon test, were conducted to compare the levels of these amino acids across the healthy group, benign tumor group, and breast cancer group. The χ2 test and Fisher's exact probability method were employed to assess the relationship between amino acid levels and breast cancer stage, grade, and chemotherapy regimen. The results indicated that there were significant differences in serum lysine (H = 36.13, P <.001) and phenylalanine (H = 34.03, P <.001) levels among the three groups. However, tryptophan levels did not show statistically significant variances. Specifically, lysine and phenylalanine levels were significantly different when comparing the healthy group with the breast cancer group and the benign tumor group with the breast cancer group. These differences were not significant when comparing the healthy group with the benign tumor group. Furthermore, there were no statistically significant distinctions observed in lysine (F = 0.836, P >.05) and phenylalanine (F = 1.466, P >.05) levels across different conventional chemotherapy regimens among the breast cancer cases studied. Serum lysine and phenylalanine levels might serve as potential biomarkers for breast cancer, and the choice of chemotherapy regimen is unlikely to impact significant changes in these amino acid levels. [ABSTRACT FROM AUTHOR]

The design and synthesis of chiral covalent organic frameworks (COFs) with controlled defect sites are highly desirable but still remain largely unexplored. Herein, we report the synthesis of a defective chiral HD‐TAPB‐DMTP COF by modifying the chiral monomer helicid (HD) into the framework of an achiral imine‐linked TAPB‐DMTP COF using a chiral monomer exchange strategy. Upon the introduction of the chiral HD unit, the obtained defective chiral HD‐TAPB‐DMTP COF not only displays excellent crystallinity, large specific surface area (up to 2338 m2/g) and rich accessible chiral functional sites but also exhibits fluorescence emission, rendering it a good candidate for discrimination of amino acids. Notably, the resultant defective chiral HD‐TAPB‐DMTP COF can be used as a fluorescent sensor for enantioselective recognition of both tyrosine and phenylalanine enantiomers in water, showing enhanced fluorescent responses for the L conformations over those of the D conformations with the enantioselectivity factors being 1.84 and 2.02, respectively. Moreover, molecular docking simulations uncover that stronger binding affinities between chiral HD‐TAPB‐DMTP COF and L‐tyrosine/L‐phenylalanine in comparison to those with D‐tyrosine/D‐phenylalanine play important roles in enantioselective determination. This work provides new insights into the design and construction of highly porous defective chiral COFs for enantioselective fluorescence recognition of amino acids. [ABSTRACT FROM AUTHOR]

Sodium humate (SH) is the sodium salt of humic acid. Our previous research has demonstrated that SH has the ability to enhance the levels of total flavonoids in various parts of lemons, including the leaves, peels, pulps, and seeds, thereby improving the quality of lemons. In the current study, the regulation effect of SH on the biosynthesis and content of lemon flavonoid compounds was examined using transcriptome sequencing technology and flavonoid metabolomic analysis. Following SH treatment, the transcriptome sequencing analysis revealed 320 differentially expressed genes (DEGs) between samples treated with SH and control (CK) samples, some of which were associated with the phenylalanine pathway by KEGG annotation analysis. The levels of seven flavonoid compounds identified in lemon peels were observed to increase, and eriocitrin and isoorientin were identified as differential metabolites (DMs, VIP > 1) using OPLS-DA analysis. The integrated analysis of transcriptomics and flavonoid metabolomics indicates that SH treatment induces alterations in gene expression and metabolite levels related to flavonoid synthesis. Specifically, SH influences flavonoid biosynthesis by modulating the activity of key enzymes in the phenylalanine pathway, including HCT (O-hydroxycinnamoyltransferase) and F5H (ferulate-5-hydroxylase). [ABSTRACT FROM AUTHOR]

The widespread presence of hierarchical asymmetric structures in nature has sparked considerable interest because of their unique functionalities. These ingenious structures across multiple scales often emerge from the transfer and amplification of asymmetry from chiral molecules under various synergistic effects. However, constructing artificial chiral asymmetric structures, particularly in developing hierarchical multicomponent structures analogous to those formed in nature through synergistic non‐covalent interactions, still presents tremendous challenges. Herein, we propose a co‐assembly strategy to fabricate hierarchical chiral mesostructures by combining a liquid crystalline block copolymer (LC‐BCP) with a small molecular amphiphile containing chiral alanine or phenylalanine as a linker. Through a classic solvent‐exchange process, chiral amphiphiles embedded within LC‐BCP finely regulate the LC ordering effect and facilitate transfer and amplification of asymmetry. Consequently, various co‐assembled structures with significant hierarchical chirality features are obtained through synergetic effects. Remarkably, subtle alterations to the side groups of amino acids in the amphiphiles effectively adjust the hierarchical morphology transition. Moreover, the covalent bonding sequence of amino acids in the amphiphiles emerges as a critical factor governing the formation of hierarchical nanofibers and multilayered vesicles exhibiting a superhelical sense. [ABSTRACT FROM AUTHOR]

Phenylketonuria is an inherited condition characterised by neurotoxic accumulation of phenylalanine (Phe). APHENITY assessed the efficacy and safety of orally administered synthetic sepiapterin in children and adults with phenylketonuria. APHENITY was a phase 3, randomised, double-blind, placebo-controlled study performed at 34 clinics, hospitals, and university sites in 13 countries. Individuals of all ages with a clinical diagnosis of phenylketonuria were eligible for inclusion if they had a blood Phe concentration of 360 μmol/L or higher at study entry, whereas individuals with hyperphenylalaninaemia due to pathogenic variants in GCH1, PTS, QDPR, SPR , and PCBD1 , consistent with a diagnosis of primary BH 4 deficiency, were excluded. Part 1 was a 14-day open-label assessment of blood Phe concentration response to sepiapterin. In part 2, sepiapterin-responsive participants were randomly assigned (1:1) by a web-response system based on a block randomisation schedule (permuted block size of 2 and 4) to 6 weeks of sepiapterin (forced-dose escalation: 20, 40, and 60 mg/kg per day per consecutive 2-week period) or placebo. The investigational drug and placebo were identical in their appearance and delivery. Dried blood samples were collected for analysis of Phe concentration on days –1, 1 (before dose was administered), 5, 10, 14, 19, 24, 28, 33, 38, and 42 in part 2, either in-clinic or at home. The primary endpoint for part 2, mean change from baseline in blood Phe after 6 weeks, was assessed in the primary analysis set of participants with at least a 30% reduction in blood Phe concentration in part 1, who took at least one dose in part 2. Safety was evaluated in all participants receiving at least one dose of treatment. The completed study is registered at EudraCT (2021-000474-29) and ClinicalTrials.gov (NCT05099640). APHENITY was conducted between Sept 30, 2021, and April 3, 2023. 187 people were assessed for eligibility, of whom 157 were enrolled. In part 1, 156 participants were assessed or evaluated, of whom 114 (73%) were sepiapterin-responsive (ie, ≥15% reduction in blood Phe from baseline). In part 2, 98 participants (49 in the placebo group and 49 in the sepiapterin group) were in the primary analysis set. There was a significant reduction of blood Phe concentration after 6 weeks of sepiapterin (–63%, SD 20) compared with placebo (1%, 29; least squares mean change –395·9 μmol/L, SE 33·8; p<0·0001). Treatment-emergent adverse events were reported in 33 (59%) of 56 participants who received sepiapterin and 18 (33%) of 54 participants who received placebo. Most treatment-emergent adverse events were mild gastrointestinal events (11 [20%] of 56 participants who received sepiapterin and ten [19%] of 54 participants who received placebo) that resolved quickly. There were no deaths and no serious or severe adverse events. Sepiapterin is a promising oral therapy for individuals with phenylketonuria, was well tolerated, and resulted in significant and clinically meaningful reductions in blood Phe concentration in participants with varying disease severity. PTC Therapeutics. [ABSTRACT FROM AUTHOR]

The current evaluation was conducted to investigate the chemical composition and functional properties of protein hydrolysates from different Satureja species. The major amino acids (mg/100 g protein) in the protein from different Satureja species were arginine (6.06–14.37), asparagine (1.39–17.06), glutamine (2.42–11.60), glutamic acid (6.34–9.32), beta‐aminoisobutyric acid (3.31–10.29), alanine (4.64–9.59), aspartic acid (5.73–9.54), proline (4.25–8.14), leucine (3.63–5.69), serine (2.64–4.83), lysine (1.89–4.56), glycine (0.96–5.27), valine (2.76–4.83), and phenylalanine (2.86–3.75). Protein hydrolysates from Satureja species exhibited comparable antioxidant activity (IC50 = 0.270–0.328 mg/mL), anti‐linoleic acid oxidation (IC50 = 0.231–0.301 mg/mL), anti‐lecithin oxidation (IC50 = 0.198–0.258 mg/mL), anti‐starch oxidation (IC50 = 0.201–0.277 mg/mL), anti‐amylase activity (IC50 = 0.314–0.337 mg/mL), and anti‐lipase activity (IC50 = 0.309–0.369 mg/mL). The physico‐chemical properties of gelatin dispersion were electrical conductivity (1197 microsiemens/cm), osmolarity (190 milliosmol/kg), surface tension (45 mN/m), particle size (179 nm), zeta potential (−48 mV), and viscosity (4.92 mPa.s). Techno‐functional characteristics of freeze‐dried gelatin particles were as follows: water content (7.68%), water solubility (84.57%), water swelling (151.33%), hygroscopicity (38.20%), hydrophobicity (6.50 μg/g), emulsification activity (68.54%), emulsification stability (57.86%), foam expansion activity (56.08%), foam stability (41.84%), oil‐holding capacity (1.96 g/g), and water‐holding capacity (4.45 g/g). Protein hydrolysate causes minor changes in the physico‐chemical and techno‐functional properties of gelatin. The current investigation introduces Satureja protein hydrolysate as a possible functional and techno‐functional ingredient for bioactive food products for treating diabetes and oxidative stress and as a natural preservative for the food industry. [ABSTRACT FROM AUTHOR]

Dihydropteridine reductase (DHPR) deficiency is a disorder that prevents regeneration of tetrahydrobiopterin (BH4), causing hyperphenylalaninemia (HPA) and low levels of neurotransmitters, including dopamine. Due to low levels of dopamine, patients present with hyperprolactinemia. Treatment consists of a phenylalanine (Phe)-restricted diet, hydroxytryptophan and levodopa (L-Dopa) supplementation, leading to a rapid normalization of prolactin (PRL) levels. We report a case of a patient with DHPR deficiency presenting with new symptomatic hyperprolactinemia and amenorrhea in adolescence despite appropriate management. The prolactinoma was confirmed with pituitary magnetic resonance imaging. The patient was started on cabergoline with rapid normalization of PRL levels and resolution of symptoms, in keeping with previous reports. Cabergoline has a stronger affinity for the D2R receptor and longer half-life than L-Dopa, leading to lactotroph apoptosis, tumor shrinkage, and rapid and maintained normalization of PRL levels, with a better side-effect profile. Patients with DHPR deficiency need to be actively monitored for symptomatic hyperprolactinemia, as L-Dopa monotherapy is insufficient to suppress PRL secretion, leading to lactotroph hypertrophy and proliferation over time and development of prolactinomas in later life. [ABSTRACT FROM AUTHOR]

A precursor feeding strategy was used for the first time in agitated microshoot cultures of Aronia × prunifolia. This strategy involved the addition of biogenetic precursors of simple phenolic acids (phenylalanine, cinnamic acid, and benzoic acid) and depsides (caffeic acid) into the culture media, with an assessment of its effect on the production of these bioactive compounds. The in vitro cultures were maintained in Murashige–Skoog medium (1 mg/L BAP and 1 mg/L NAA). Precursors at five concentrations (0.1, 0.5, 1.0, 5.0, and 10.0 mmol/L) were fed into the medium at the time of culture initiation (point "0") and independently on the 10th day of growth cycles. The contents of 23 compounds were determined in methanolic extracts of biomass collected after 20 days of growth cycles using an HPLC method. All extracts contained the same four depsides (chlorogenic, neochlorogenic, rosmarinic, and cryptochlorogenic acids) and the same four simple phenolic acids (protocatechuic, vanillic, caffeic, and syringic acids). Chlorogenic and neochlorogenic acids were the predominant compounds in all extracts (max. 388.39 and 263.54 mg/100 g d.w.). The maximal total contents of all compounds were confirmed after feeding with cinnamic acid (5 mmol/L, point "0") and caffeic acid (10 mmol/L, point "0"), which caused a 2.68-fold and 2.49-fold increase in the contents of the estimated compounds vs. control cultures (603.03 and 558.48 mg/100 g d.w., respectively). The obtained results documented the efficacy of the precursor feeding strategy in enhancing the production of bioactive compounds in agitated cultures of A. × prunifolia and suggest a potential practical application value. [ABSTRACT FROM AUTHOR]

• Ozonation enhanced the formation potential of regulated DBPs from Phe chlorination. • CH with highest yield of 21.31+1.05 ug/mgPhe was enhanced to 3 times after ozonation. • The DBPs formation rates in the first 6 h were much higher than subsequent time. • Br− promoted brominated DBPs generation and elevated the total cytotoxicity. • Ozonation enhanced the BIF of THMs, while reduced that of DHAAs. As a strong oxidizing agent, ozone is used in some water treatment facilities for disinfection, taste and odor control, and removal of organic micropollutants. Phenylalanine (Phe) was used as the target amino acid to comprehensively investigate variability of disinfection byproducts (DBPs) formation during chlorine disinfection and residual chlorine conditions subsequent to ozonation. The results showed that subsequent to ozonation, the typical regulated and unregulated DBPs formation potential (DBPsFP), including trichloromethane (TCM), dichloroacetonitrile (DCAN), chloral hydrate (CH), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), and trichloroacetamide (TCAcAm) increased substantially, by 2.4, 3.3, 5.6, 1.2, 2.5, and 6.0 times, respectively, compared with only chlorination. Ozonation also significantly increased the DBPs yield under a 2 day simulated residual chlorine condition that mimicked the water distribution system. DBPs formations followed pseudo first order kinetics. The formation rates of DBPs in the first 6 hr were higher for TCM (0.214 hr−1), DCAN (0.244 hr−1), CH (0.105 hr−1), TCAcAm (0.234 hr−1), DCAA (0.375 hr−1) and TCAA (0.190 hr−1) than thereafter. The peak DBPsFP of TCM, DCAN, CH, TCAcAm, DCAA, and TCAA were obtained when that ozonation time was set at 5–15 min. Ozonation times > 30 min increased the mineralization of Phe and decreased the formation of DBPs upon chlorination. Increasing bromine ion (Br−) concentration increased production of bromine- DBPs and decreased chlorine-DBPs formation by 59.3%–92.2%. Higher ozone dosages and slight alkaline favored to reduce DBP formation and cytotoxicity. The ozonation conditions should be optimized for all application purposes including DBPs reduction. [Display omitted] [ABSTRACT FROM AUTHOR]

The current study applied electrospun fibers containing 8-hydroxyquinoline-5-sulfonic acid (8-HQS) (100, 150, and 200 mg L−1) and silver nitrate (AgNO3) (15 and 20 mg L−1) to enhance the longevity and qualitative parameters of two cyclamen cultivars. The results indicated that the vase life of the flowers treated with 20 mg L−1 AgNO3 and 200 mg L−1 8-HQS was higher than that of the other treatments (16 days). Cyclamens treated with 8-HQS (100 mg L−1) + AgNO3 (15 mg L−1) and 8-HQS (100 mg L−1) + AgNO3 (20 mg L−1) had lower polyphenol oxidase (PPO) activity than the control group. Also, it was observed that the higher phenylalanine ammonia-lyase (PAL) enzyme activity of cyclamens in the 8-HQS (150 mg L−1) + AgNO3 (15 mg L−1) treatment was longer than that of the other treatments and control groups. Treatment with 100 mg L−1 8-HQS and 20 mg L−1 AgNO3 showed higher peroxidase (POD) activity than the different treatments. This research indicated that adding AgNO3 and 8-HQS to electrospun fibers is a promising method for enhancing the longevity and maintaining the quality of these cut flowers. [ABSTRACT FROM AUTHOR]

Postharvest ethylene accumulation and lignification are significant issues affecting the storage quality of fresh faba beans, resulting in rapid quality decline. However, there is still a lack of effective preservation methods to preserve the quality of faba beans during storage. This study aimed to investigate the regulation of lignification in faba beans during storage using a high-efficiency ethylene remover (HEER), examining physiological responses, key enzyme activities, and transcriptomic changes. Results showed that the HEER treatment inhibited the lignification, reducing it by 45% and lowering the respiratory rate of fresh pods by 32.8% during storage. Additionally, the HEER treatment suppressed respiration rates and the activities of lignin synthesis-related enzymes, including phenylalanine ammonia-lyase (from 353.73 to 246.60 U/g), cinnamic acid-4-hydroxylase (from 635.86 to 125.00 U/g), 4-coumarate: coenzyme A ligase (from 1008.57 to 516.52 U/g), and cinnamyl-alcohol dehydrogenase (from 129.42 to 37.12 U/g), thus slowing lignin accumulation. During storage, the hardness of fresh faba bean increased by 9.79% from the initial period, being 1.44 times higher than that of HEER. On days 8 and 16 of storage, the respiratory rate of the treated beans decreased by 24.38% and 4.12%, respectively. Physiological and enzyme activity analyses indicated that HEER treatment-induced increase in hardness was associated with the phenylpropanoid metabolic pathway. Moreover, the HEER significantly down-regulated the expression of several key genes, namely FaPAL, FaC4H, and FaCAD. This study helps to deepen the understanding of the inhibition of lignification by HEER and provide new insights for the development of preservation technology of faba bean. [ABSTRACT FROM AUTHOR]

Oxidative stress is a major factor that limits the development of the poultry industry. Ferulic acid (FA) has an antioxidant effect in birds, but the mechanism is not fully understood. In this study, we stimulated oxidative stress in 28-day-old female Linwu ducks by lipopolysaccharide (LPS) and fed them a diet supplemented with FA for 28 days. Results showed that FA alleviated LPS-induced growth performance regression, oxidative stress, and microbiota imbalance in ducks. An integrated metagenomics and metabolomics analysis revealed that s_Blautia_obeum, s_Faecalibacterium_prausnitzii, s_gemmiger_formicilis, and s_Ruminococcaceae_bacterium could be the biomarkers in the antioxidant effect of FA, which interacted with dihydro-3-coumaric acid, L-phenylalanine, and 13(S)-HODE, and regulated the phenylalanine metabolism and PPAR signaling pathway. This study revealed the mechanism of the antioxidant effect of FA, which provided evidence of applying FA as a new antioxidant in commercial duck production. [ABSTRACT FROM AUTHOR]

AbstractThis study aimed to evaluate the relationship between aromatic amino acids (AAAs), – phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) – and coronary artery disease (CAD) in a prospective study involving 2970 participants undergoing coronary angiography at Beijing Hospital. Serum levels of Phe, Tyr and Trp were analysed. The cross-sectional data revealed that serum Tyr and Trp levels were significantly and inversely associated with CAD. During a median follow-up period of 44 months, 343 major adverse cardiovascular events (MACEs) and 138 all-cause deaths were recorded. MACE included myocardial infarction, stroke, revascularisation and all-cause mortality. Low serum Trp levels predicted an increased risk of MACE and death. High serum Phe levels were linked to an increased risk of MACE, while low Tyr levels were associated with a higher risk of death. Collectively, our findings underscore a close correlation between AAAs and CAD, as well as their potential predictive value for adverse cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

SUMMARY: The conquest of land posed severe problems to plants which they had to cope with by adapting biosynthetic capacities. Adaptations to respond to UV irradiation, water loss, pathogen and herbivore defense, and the earth's pull were essential. Chemical compounds alleviating these problems can be synthesized by the phenylpropanoid pathway, the core of which are three enzymes: phenylalanine ammonia‐lyase (PAL), cinnamic acid 4‐hydroxylase, and 4‐coumaric acid coenzyme A‐ligase (4CL). The genomes of model organisms, Chara braunii as aquatic alga and the two bryophytes Physcomitrium patens and Marchantia polymorpha, were searched for sequences encoding PAL and 4CL and selected sequences heterologously expressed in Escherichia coli for biochemical characterization. Several possible isoforms were identified for both enzymes in Marchantia polymorpha and Physcomitrium patens, while only one or two isoforms could be retrieved for Chara braunii. Active forms of both enzymes were found in all three organisms, although the catalytic efficiencies varied in a wide range. l‐Phenylalanine was accepted as best substrate by all PAL‐like enzymes, despite annotations in some cases suggesting different activities. The substrate spectrum of 4CLs was more diverse, but caffeic and/or 4‐coumaric acids generally were the best‐accepted substrates. Our investigations show that PAL and 4CL, important enzymes for the formation of phenolic compounds, are present and active in extant charophytes and bryophytes as model organisms for the conquest of land. Significance Statement: Upon terrestrialization, plants have profited from an effective phenylpropanoid metabolism enabling them to cope with stressors on land. Essential enzymes, phenylalanine ammonia‐lyase, and 4‐coumaric acid coenzyme A‐ligase are present and active in the charophyte Chara braunii (shown for the first time) and the bryophytes Marchantia polymorpha and Physcomitrium patens and have been characterized on molecular and biochemical levels. [ABSTRACT FROM AUTHOR]

This study aimed to provide novel information on the impact of indigenous non-Saccharomyces yeasts, including Metschnikowia chrysoperlae, Metschnikowia sinensis/shanxiensis, Metschnikowia pulcherrima, Lachancea thermotolerans, Hanseniaspora uvarum, Hanseniaspora guilliermondii, and Pichia kluyveri, on metabolites related to the metabolism of tryptophan, phenylalanine, and tyrosine. The experiment included two fermentation practices: monoculture and sequential fermentation with commercial Saccharomyces cerevisiae, using sterile Maraština grape juice. A targeted approach through ultrahigh-resolution liquid chromatography associated with mass spectrometry was used to quantify 38 metabolites. All the indigenous yeasts demonstrated better consumption of tryptophan in monoculture than in interaction with S. cerevisiae. M. sinensis/shanxiensis was the only producer of indole-3-carboxylic acid, while its ethyl ester was detected in monoculture fermentation with H. guilliermondii. H. guilliermondii consumed the most phenylalanine among the other isolates. 5-hydroxy-L-tryptophan was detected in fermentations with M. pulcherrima and M. sinensis/shanxiensis. M. pulcherrima significantly increased tryptophol content and utilised tyrosine in monoculture fermentations. Sequential fermentation with M. sinensis/shanxiensis and S. cerevisiae produced higher amounts of N-acetyl derivatives of tryptophan and phenylalanine, while H. guilliermondii-S. cerevisiae fermentation resulted in wines with the highest concentrations of L-kynurenine and 3-hydroxyanthranilic acid. P. kluyveri produced the highest concentration of N-acetyl-L-tyrosine in monoculture fermentations. These findings highlight the different yeast metabolic pathways. [ABSTRACT FROM AUTHOR]

Background: Lifelong management of phenylketonuria (PKU) centers on medical nutrition therapy, including dietary phenylalanine (Phe) restriction in addition to Phe-free or low-Phe medical foods/protein substitutes. Studies have reported low bone mineral density (BMD) in mixed-age PKU populations, possibly related to long-term Phe restriction. Therefore, a meta-analysis investigating BMD specifically in adults with PKU was conducted. Methods: Studies reporting BMD-related outcomes were identified from a systematic literature review evaluating somatic comorbidities experienced by adults with PKU on a Phe-restricted diet (searched February 1, 2022, updated November 1, 2023). Risk of study bias was assessed (Scottish Intercollegiate Guidelines Network checklists). The primary outcome of the meta-analysis was pooled mean BMD Z-scores of different bones. Secondary outcomes were the prevalence of low BMD Z-scores at pre-specified thresholds. Subgroup analyses of mean BMD Z-scores (decade of study publication, controlled versus uncontrolled blood Phe levels, gender) were conducted. Results: BMD-related data from 4097 individuals across 10 studies rated as at least acceptable quality were included. Mean BMD Z-scores were statistically significantly lower compared with an age-matched control or reference (non-PKU) population, across bones, but still within the expected range for age (> -2.0): lumbar spine (seven studies, n = 304), -0.63 (95% confidence interval (CI): -0.74, -0.52); femoral neck (four studies, n = 170), -0.74 (95% CI: -1.25, -0.22); radius (three studies, n = 114), -0.77 (95% CI: -1.21, -0.32); total body (four studies, n = 157), -0.61 (95% CI: -0.77, -0.45). The small number of observations in the subgroup analyses resulted in a high degree of uncertainty, limiting interpretation. Estimated prevalence of BMD Z-scores ≤ -2.0 was 8% (95% CI: 5%, 13%; four studies, n = 221) and < -1.0 was 42% (95% CI: 35%, 51%; five studies, n = 144). Conclusions: Adults with PKU had lower BMD Z-scores than the reference (non-PKU) population but < 1 in 10 were below the expected range for age. The low number of studies prevents identification of which population characteristics are most impacting BMD. This meta-analysis was supported by BioMarin Pharmaceutical Inc., Novato, CA and is registered with the Research Registry (reviewregistry1476). [ABSTRACT FROM AUTHOR]

[Display omitted] The adsorption properties of a carbon sorbent in relation to sulfosalicylic acid in an individual solution and with an added amino acid (arginine or phenylalanine) were determined. It has been shown that the addition of arginine to an aqueous solution of sulfosalicylic acid leads to an increase in the amount of sulfosalicylic acid adsorbed on the carbon sorbent. The sorbents modified in the presence of amino acids showed high adsorption capacity for the methylene blue dye. [ABSTRACT FROM AUTHOR]

Simple Summary: Phenylalanine/tyrosine ammonia-lyase (PTAL) is a bifunctional enzyme that can deaminate both phenylalanine and tyrosine. To explore the efficiency of lignin biosynthesis with the bifunctional enzyme, we applied a comparable experimental system consisting of transgenic and non-transgenic Arabidopsis and crop-weedy rice hybrid (CWRH) lineages to analyze lignin-biosynthesis associated metabolites. We found substantial increases in EPSPS gene expression, phenylalanine and tyrosine contents, total lignin and its monolignols (lignin units), and biomass in the experimental materials. Importantly, these results demonstrated that overexpressing the EPSPS genes in Arabidopsis and CWRH lineages increased phenylalanine and tyrosine levels, which significantly promoted lignin biosynthesis and biomass production in the transgenic CWRH lineages serve as a sink for plant carbon fixation. These findings are important for a better understanding of the PAL and PTAL's functions in different plant species, in addition to efficient carbon fixation by genetic engineering in plants. Lignin is a key metabolite for terrestrial plants. Two types of aromatic amino acids, phenylalanine (Phe) and tyrosine (Tyr), serve as the precursors for lignin biosynthesis. In most plant species, Phe is deaminated by Phe ammonia-lyase (PAL) to initiate lignin biosynthesis, but in grass species, Phe and Tyr are deaminated by Phe/Tyr ammonia-lyase (PTAL). To understand the efficiency of PAL and PTAL, we used transgenic and non-transgenic Arabidopsis with PAL and crop-weedy rice hybrids (CWRH) with PTAL to analyze lignin-biosynthesis-associated metabolites. The transgenic plants overexpressed the exogenous 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene, whereas the non-transgenic plants normally expressed the endogenous EPSPS gene. Our results show significantly increased Phe/Tyr contents in transgenic Arabidopsis and CWRH plants, leading to substantially increased lignin and biomass. In addition, the PTAL pathway promotes a much greater proportion of increased lignin and biomass in transgenic CWRH than in transgenic Arabidopsis lineages. Evidently, more efficient lignin biosynthesis characterized the grass species possessing the PTAL pathway. These findings are important for a better understanding of the PAL and PTAL's functions in the phenylpropanoid metabolic pathways in the evolution of plant species. These findings also have great value for implications such as effective carbon fixation by enhancing lignin biosynthesis through genetic engineering of their key genes in appropriately selected plant species. [ABSTRACT FROM AUTHOR]

Citrus aurantium L., sometimes known as "sour orange," is an important Chinese herb with young, immature fruits, or "zhishi," that are high in synephrine. Synephrine is a commonly utilized natural chemical with promising applications in effectively increasing metabolism, heat expenditure, energy level, oxidative fat, and weight loss. However, little is known about the genes and pathways involved in synephrine production during the critical developmental stages of C. aurantium L., which limits the development of the industry. According to this study, the concentration of synephrine gradually decreased as the fruit developed. Transcriptome sequencing was used to examine the DEGs associated with synephrine connections and served as the foundation for creating synephrine-rich C. aurantium L. Comparisons conducted between different developmental stages to obtain DEGs, and the number of DEGs varied from 690 to 3,019. Tyrosine and tryptophan biosynthesis, glycolysis/gluconeogenesis, pentose phosphate pathway, phenylalanine, and tyrosine metabolism were the main KEGG pathways that were substantially enriched. The results showed that 25 genes among these KEGG pathways may be related to synephrine synthesis. The WGCNA and one-way ANOVA analysis adoption variance across the groups suggested that 11 genes might play a crucial role in synephrine synthesis and should therefore be further analyzed. We also selected six DEGs at random and analyzed their expression levels by RT-qPCR, and high repeatability and reliability were demonstrated by our finished RNA-seq study results. These results may be useful in selecting or modifying genes to increase the quantity of synephrine in sour oranges. [ABSTRACT FROM AUTHOR]

Amino acid (AA)-related inherited metabolic disorders (IMDs) and urea cycle disorders (UCDs) require strict dietary management including foods low in protein such as fruits, vegetables and starchy roots. Despite this recommendation, there are limited data on the AA content of many of these foods. The aim of this study is to describe an analysis of the protein and AA content of a range of fruits, vegetables and starchy roots, specifically focusing on amino acids (AAs) relevant to AA-related IMDs such as phenylalanine (Phe), methionine (Met), leucine (Leu), lysine (Lys) and tyrosine (Tyr). AA analysis was performed using high-performance liquid chromatography (HPLC) on 165 food samples. Protein analysis was also carried out using the Dumas method. Foods were classified as either 'Fruits', 'Dried fruits', 'Cruciferous vegetables', 'Legumes', 'Other vegetables' or 'Starchy roots'. 'Dried fruits' and 'Legumes' had the highest median values of protein, while 'Fruits' and 'Cruciferous vegetables' contained the lowest median results. 'Legumes' contained the highest and 'Fruits' had the lowest median values for all five AAs. Variations were seen in AA content for individual foods. The results presented in this study provide useful data on the protein and AA content of fruits, vegetables and starchy roots which can be used in clinical practice. This further expansion of the current literature will help to improve diet quality and metabolic control among individuals with AA-related IMDs and UCDs. [ABSTRACT FROM AUTHOR]

Low temperature is a major environmental factor that negatively affects the growth and productivity of plants, such as the tropical fruit Cape gooseberry (Physalis peruviana L.), which is susceptible to cold stress. Therefore, to investigate the effect of the amino acid L-phenylalanine (Phe), L-cysteine (Cys), or sodium selenite (Se) on enhancing antioxidant activities, experiments were conducted on the phenolic compounds, proline content, and membrane stability of Cape gooseberry seedlings under low-temperature stress. The seedlings were exposed for 48 h to a low temperature (4 °C) followed by 24 h of optimal growth conditions. In seedlings treated with Se, we found a high relative water content, good membrane integrity, low ion leakage, and hydrogen peroxide. Additionally, this treatment led to the improvement of photosynthetic pigments and antioxidant activity. The analysis of seedlings under cold stress showed that the Phe enhanced the stomatal conductance and phenol content. Furthermore, low concentrations of Cys resulted in the production of proline and flavonoids, which reduced the negative effects of environmental stress on seedlings and maintained cell membrane integrity. Overall, in this experiment, the use of Se and low concentrations of Cys had a positive effect on the amount of antioxidant compounds, which improved seedling growth under stress conditions. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We present an economic and straightforward method to introduce 13C-19F spin systems into the deuterated aromatic side chains of phenylalanine as reporters for various protein NMR applications. The method is based on the synthesis of [4-13C, 2,3,5,6-2H4] 4-fluorophenylalanine from the commercially available isotope sources [2-13C] acetone and deuterium oxide. This compound is readily metabolized by standard Escherichia coli overexpression in a glyphosate-containing minimal medium, which results in high incorporation rates in the corresponding target proteins. [ABSTRACT FROM AUTHOR]

Background: Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). Methods: To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann–Whitney U test, p < 0.05) analyses. Results: Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated. Conclusions: This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason. [ABSTRACT FROM AUTHOR]

Copyright of Acta Agriculturae Zhejiangensis is the property of Acta Agriculturae Zhejiangensis Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Agriculturae Zhejiangensis is the property of Acta Agriculturae Zhejiangensis Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract The kidney is considered the main site for the net release of Tyrosine (Tyr) to the circulation through hydroxylation of Phenylalanine (Phe) using phenylalanine hydroxylase enzyme. In chronic kidney disease (CKD) patients the enzyme activity is impaired, therefore the serum concentration ratio of Tyr/Phe is reduced compared to healthy individuals. This motivates us to develop a cost effective, green, simple, sensitive, and selective HPTLC method to measure the levels of Tyr and Phe in serum samples. The analysis was carried out using acetonitrile: ethanol: 25% ammonia solution: ethyl acetate (6.5: 1.5: 1: 0.5) as a mobile phase. Rf values were 0.55 ± 0.05 for Phe and 0.39 ± 0.05 for Tyr. Densitometry scanning was performed using UV detector and dual wavelengths of 210 and 225 nm were obtained. A linear correlation was observed between the levels of Phe and Tyr, ranging from 50 to 700 ng band− 1 and 50 to 600 ng band− 1, respectively, under the optimum conditions. The method selectivity, linearity, precision, accuracy, and robustness were all confirmed in accordance with ICH recommendations. Calculations of the separation and resolution factors, number of theoretical plates, and height equivalent to theoretical plates prove to the chromatographic system accuracy and high separation efficiency. The developed method exhibits an acceptable eco-scale when measuring the method greenness using AGREE and GAPI softwares. It was applied for the determination of Phe and Tyr concentrations in human serum samples.

Abstract Many studies have focused on the effects of small molecules, such as amino acids, on metabolism under hypoxia. Recent findings have indicated that phenylalanine levels were markedly elevated in adaptation to chronic hypoxia. This raises the possibility that phenylalanine treatment could markedly improve the hypoxic endurance. However, the importance of hypoxia-regulated phenylalanine is still unclear. This study investigates the role of phenylalanine in hypoxia adaptation using a hypoxic zebrafish model and multi-omics analysis. We found that phenylalanine-related metabolic pathways are significantly up-regulated under hypoxia, contributing to enhanced hypoxic endurance. Phenylalanine treatment reduced ROS levels, improved mitochondrial oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) in hypoxic cells. Western blotting revealed increased phenylalanine uptake via L-type amino transporters (LAT1), activating the LKB1/AMPK signaling pathway. This activation up-regulated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and the Bcl-2/Bax ratio, while down-regulating uncoupling protein 2 (UCP2), thereby improving mitochondrial function under hypoxia. This is the first comprehensive multi-omics analysis to demonstrate phenylalanine’s crucial role in hypoxia adaptation, providing insights for the development of anti-hypoxic drugs. Graphical Abstract

Abstract This study aimed to analyze whether early‐treated adults with phenylketonuria (PKU) can subjectively sense high phenylalanine (Phe) concentrations and whether a possible impact of Phe on objective measures of cognitive performance and mood reflects patients' self‐perception. Data from the PICO study, a randomized, placebo‐controlled, double‐blind, crossover trial, were analyzed. Twenty‐eight adults with PKU received either Phe capsules or placebo in two 4‐week intervention periods in a randomized order, with a 4‐week washout in between. The median Phe level increased from 852 μmol/L (interquartile range: 345) to 1455 μmol/L (interquartile range: 369). Neuropsychological assessments were performed at four study visits. At the end of the last study visit, patients were asked whether they could discern the Phe intervention period. Seven of 28 (25%) patients stated that they could not discern between the Phe and the placebo period. Twenty‐one of 28 (75%) patients subjectively thought to sense high Phe levels. Of the 21 patients, 12 (57%) correctly identified the Phe period, whereas 9 (43%) received placebo at the time when they thought they would receive the high Phe load. Binomial tests showed that the probability of 12 out of 21 is p = 0.140, and 12 out of 28 is p = 0.113. The “Right‐Guess” group showed significantly higher Phe changes than the “Wrong‐Guess” group. Cognitive performance and standardized mood assessment did not significantly differ, and both groups reported similar subjective negative impact on cognition and mood. In conclusion, adults with early‐treated PKU cannot effectively identify high Phe levels, although some individuals may be able to perceive more pronounced increases in Phe levels.