Amino Acids Citrulline Research Articles

Plasma metabolites associated with plasma P‐tau181 in preclinical Alzheimer's disease

AbstractBackgroundAlzheimer's disease (AD) pathogenesis is not restricted to amyloid‐beta, Aβ, and tau pathologies but involves dysregulation in diverse cellular and molecular processes. Numerous metabolomic studies revealed plasma metabolite alterations in AD individuals compared to healthy controls. Nevertheless, plasma P‐tau181, an established biomarker for AD diagnosis and prognosis, has been described to reflect initial multiple cortical region Aβ deposition in cognitively intact adults. The current study aims to identify plasma metabolites associated with plasma P‐tau181 at the preclinical stage and better understand the associated biochemical mechanisms for AD pathogenesis.MethodIn the current study, 100 older adults with no objective cognitive impairment, MoCA and MMSE ≥ 26, from the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort, comprising 65 CI Aβ‐ (cognitively intact normal brain Aβ) and 35 CI Aβ+ (cognitively intact higher brain Aβ) individuals, were assessed for plasma P‐tau181, via ultra‐sensitive Quanterix Simoa technology, and plasma metabolites, via mass spectrometry‐based BIOCRATES kit, and then investigated for associations, both before and after adjusting for confounding variables, in the study groups. Additionally, P‐tau181‐associated plasma metabolites were evaluated using the receiver operating characteristic (ROC) curves for the potential to classify brain Aβ status.ResultIn the entire cohort, significant positive associations of plasma metabolites, including acylcarnitines, amino acid citrulline, and three biogenic amines (creatinine, kynurenine and SDMA), were observed with P‐tau181 and similar associations, except for kynurenine, were detected in CI Aβ‐. In contrast, in CI Aβ+, only acylcarnitine, AC(10:3), was found to have a positive association with P‐tau181 and further, upon including AC(10:3), the AUC for P‐tau181 (AUC=70.9%) potentially outperformed (AUC=76.2%), which additionally topped to 83.9% when combined with a base model (Abstract Figure).ConclusionThese findings suggest that the higher the plasma P‐tau181, the higher the medium chain acylcarnitine, AC(10:3), in plasma in cognitively intact older adults at risk for AD, indicating a link between early Aβ pathology and fatty acid oxidation mediated energy metabolism pathway. Additionally, associated metabolite strengthens the significance of P‐tau181 in classifying brain Aβ status in cognitively intact older adults. Therefore, plasma P‐tau181‐associated plasma metabolite may serve as potential predictive marker for preclinical AD pathogenesis.

Classification of colorectal cancer patients based on serum micronutrients: An exploratory investigation

BackgroundColorectal cancer (CRC) is a growing global health challenge with a multifactorial etiology encompassing genetic susceptibility, nutrition, and inflammation in the bowel. ObjectiveTo examine micronutrient status in CRC patients undergoing CRC resection. DesignWe performed a case-control study including 13 consecutive CRC patients and 10 healthy controls (CTRL) comparing the serum levels of 29 micronutrients, namely Copper, Zinc, Selenium, Chromium, Manganese, Carnitine, Choline, Inositol, Methylmalonic acid (MMA), Vitamin (Vit) B1, Vit B2, Vit B3, Vit B5, Vit B6, Vit C, Vit A, Vit D3, Vit E, Vit K1, Vit K2 and the amino acids Serine, Valine, Leucine, Isoleucine, Asparagine, Glutamine, Arginine, Citrulline and Cysteine. ResultsAfter considering the effect of age and sex, copper, arginine, and cysteine were increased, while zinc, selenium, chromium, Vit B1, Vit K1, and Vit A were decreased in CRC patients in comparison with CTRL. Zinc levels perfectly predicted the diagnosis of CRC, and were associated with lymph nodes (pN), of the pTNM staging. Copper levels in serum were strongly associated with the pathological pTNM staging of CRC. ConclusionThough this is a preliminary study that needs confirmation with a larger longitudinal cohort, our results show that serum micronutrients are linked to tumor growth, likely caused by increased demand from tumor tissue associated with an aberrant cell proliferation and changes in the antioxidant function.

Determination of the Effects of Pear-Morchella Intercropping Mode on M. sextelata Quality, Yield, and Soil Microbial Community.

The intercropping of Morchella in pear orchards has important production value in improving the utilization rate and economic benefits of the orchard; however, there is little research on the intercropping model of pear-Morchella. In this study, metabolomics analysis found that compared with greenhouse cultivation, there were 104 and 142 metabolites significantly increased and decreased in the intercropping mode of M. sextelata, respectively. Among them, there was a significant accumulation of amino acids (phenylalanine, lysine, proline, citrulline, and ornithine), sugars (arabinitol and glucosamine), and organic acids (quinic acid, fumaric acid, and malic acid) related to the unique taste of Morchella in intercropping cultivation. In addition, research on the cultivation model using exogenous nutrient bags indicated that placing the density of six exogenous nutrient bags per square meter was most suitable for yield formation. Adding pear sawdust to the nutrient bags (PN) significantly increased the yield of morel per unit area. Moreover, soil microbial community analysis showed that fungal alpha diversity dramatically declined in PN-cultivated soil, which decreased the relative abundance of soil-borne fungal pathogens, including Fusarium and Aspergillus. Some beneficial soil bacteria abundance increased in the PN-used soil, such as Pedobacter, Pseudomonas, and Devosia. This study provides novel insights into the effects of intercropping on the internal quality of Morchella and enriches the theoretical knowledge on the consummation of the pear-Morchella model formation, further improving agricultural resource utilization efficiency and crop productivity.

PolyCitrulline Modified Glassy Carbon Electrode as a Voltammetric Sensor for the Simultaneous Determination of Metabolic Syndrome Biomarkers-Uric Acid and Tyramine

This article describes the development of a simple and sensitive voltammetric sensor for the simultaneous determination of Uric acid (UA) and Tyramine (TYM), which act as metabolic syndrome (Mts) biomarkers. The electropolymer of the naturally occurring amino acid citrulline (Cit) has been employed as the electrode modifier in this sensor. Glassy carbon electrode modified with poly citrulline has been characterized with the aid of techniques such as scanning electron microscopy (SEM) and SEM-energy dispersive X-ray analysis, surface area calculations and electrochemical impedance spectroscopy. Studies were carried out to optimize parameters like the cycles of polymerisation, supporting electrolyte and its pH. The sensor which offers fast determination of the analytes using square wave voltammetry possesses a limit of detection 1.32 × 10−8 M and 4.20 × 10−8 M for UA and TYM, respectively. The applicability of the sensor in body fluids has been proved through spike recovery analysis in artificial blood serum and urine samples. Interference on the voltammetric signals created by some dominant coexisting species of the analytes was found to be tolerable.

Circulating amino acid signature features urea cycle alterations associated with coronary artery disease

Coronary artery disease (CAD) remains a leading cause of death worldwide and imposes a substantial socioeconomic burden on healthcare. Improving risk stratification in clinical practice could help to combat this burden. As amino acids are biologically active metabolites whose involvement in CAD remains largely unknown, this study investigated associations between circulating amino acid levels and CAD phenotypes. A high-coverage quantitative liquid chromatography-mass spectrometry approach was applied to acquire the serum amino acids profile of age- and sex-coarsened-matched patients with CAD (n = 46, 66.9 years, 74.7% male) and healthy individuals (n = 120, 67.4 years, 74.7% male) from the COmPLETE study. Multiple linear regressions were performed to investigate associations between amino acid levels and (a) the health status (CAD vs. healthy), (b) the number of affected coronary arteries, or (c) the left ventricular ejection fraction. Regressions were adjusted for age, sex, daily physical activity, sampling, and fasting time. Urea cycle amino acids (ornithine, citrulline, homocitrulline, aspartate, and arginine) were significantly and negatively associated with CAD, the number of affected coronary arteries, and the left ventricular ejection fraction. Lysine, histidine, and the glutamine/glutamate ratio were also significantly and negatively associated with the CAD phenotypes. Overall, patients with CAD displayed lower levels of urea cycle amino acids, highlighting a potential role for urea cycle amino acid profiling in cardiovascular risk stratification.Trial registrationThe study was registered on https://www.clinicaltrials.gov (NCT03986892) on June 5, 2019.

CLASSIFICATION OF COLORECTAL CANCER PATIENTS BASED ON SERUM MICRONUTRIENTS: AN EXPLORATORY INVESTIGATION

Abstract Introduction/Objective Colorectal cancer (CRC) is a growing global health challenge with a multifactorial etiology encompassing genetic susceptibility, nutrition, and inflammation in the bowel. To examine micronutrient status in CRC patients undergoing CRC resection. Methods/Case Report We performed a pilot case-control study including 13 consecutive CRC patients and 10 healthy controls (CTRL) comparing the serum levels of 29 micronutrients, namely Copper, Zinc, Selenium, Chromium, Manganese, Carnitine, Choline, Inositol, Methylmalonic acid (MMA), Vitamin (Vit) B1, Vit B2, Vit B3, Vit B5, Vit B6, Vit C, Vit A, Vit D3, Vit E, Vit K1, Vit K2 and the amino acids Serine, Valine, Leucine, Isoleucine, Asparagine, Glutamine, Arginine, Citrulline and Cysteine. The analysis of trace metals (copper, zinc, selenium, chromium, manganese) in serum was done using the Inductively coupled plasma mass spectrometry (ICP-MS) methodology using the Agilent 8900 QQQ instrument. The analysis of serum water-soluble and fat-soluble vitamins and amino acids was conducted using the LC/MS (Xevo-TQ-XS) mass spectrometer (WBA0127). Elution of the fat-soluble vitamins was performed using a solid-phase extraction system with an OASIS Prime HLB plate containing 10 mg of sorbent per well, in a Waters vacuum manifold equipped with a waste collection plate. Comparison among continuous biological variables was carried out by multivariate ANOVA model (MANOVA), accounting for the effect of sex and age Results (if a Case Study enter NA) After considering the effect of age and sex, copper, arginine, and cysteine were increased, while zinc, selenium, chromium, Vit B1, Vit K1, and Vit A were decreased in CRC patients in comparison with CTRL. Zinc levels perfectly predicted the diagnosis of CRC, and was associated with lymph nodes (pN), of the pTNM staging. Copper levels in serum was strongly associated with the pathological pTNM staging of CRC. Conclusion Though this is a preliminary study which needs confirmation with a larger longitudinal cohort, our results show that serum micronutrients are linked to tumor growth, likely caused by increased demand from tumor tissue associated with an aberrant cell proliferation and changes in the antioxidant function.

Nutritional status and extended metabolic screening in Egyptian children with uncomplicated type 1 diabetes

Nutritional status assessment, including amino acids, carnitine, and acylcarnitine profile, is an important component of diabetes care management, influencing growth and metabolic regulation. A designed case–control research included 100 Egyptian participants (50 T1DM and 50 healthy controls) aged 6 to 18 years old. The participants' nutritional status was assessed using the Body Mass Index (BMI) Z-score. Extended metabolic screening (EMS) was performed using a high-performance liquid chromatography-electrospray ionization-mass spectroscopy system to evaluate the levels of 14 amino acids, free carnitine, and 27 carnitine esters. T1DM children had considerably lower anthropometric Z-scores than the control group, with 16% undernutrition and 32% short stature. Total aromatic amino acids, phenylalanine, phenylalanine/tyrosine ratio, proline, arginine, leucine, isoleucine, free carnitine, and carnitine esters levels were considerably lower in the diabetic group, suggesting an altered amino acid and carnitine metabolism in type 1 diabetes. BMI Z-score showed a significant positive correlation with Leucine, Isoleucine, Phenylalanine, Citrulline, Tyrosine, Arginine, Proline, free carnitine, and some carnitine esters (Acetylcarnitine, Hydroxy-Isovalerylcarnitine, Hexanoylcarnitine, Methylglutarylcarnitine, Dodecanoylcarnitine, Tetradecanoylcarnitine, and Hexadecanoylcarnitine). HbA1c% had a significant negative correlation with Total aromatic amino acids, Branched-chain amino acid/Total aromatic amino acids ratio, Glutamic Acid, Citrulline, Tyrosine, Arginine, Proline, and certain carnitine esters (Propionylcarnitine, Methylglutarylcarnitine, Decanoylcarnitine, Octadecanoylcarnitine and Octadecenoylcarnitine), suggest that dysregulated amino acid and carnitine metabolism may be negatively affect the glycaemic control in children with TIDM. In conclusion, regular nutritional assessments including EMS of T1DM patients are critical in terms of diet quality and protein content for improved growth and glycemic management.

Exploring the Fermentation Products, Microbiology Communities, and Metabolites of Big-Bale Alfalfa Silage Prepared with/without Molasses and Lactobacillus rhamnosus

The influence of molasses (M) and Lactobacillus rhamnosus (LR) on fermentation products, microbial communities, and metabolites in big-bale alfalfa silage was investigated. Alfalfa (Medicago sativa L.) was harvested at the third growth stage during the flowering stage in the experimental field of Linhui Grass Company from Tongliao City, Inner Mongolia. An alfalfa sample without additives was used as a control (C). M (20 g/kg) and LR (106 cfu/g) were added either alone or in combination. Alfalfa was fermented for 7, 14, and 56 d. Lactic acid content in the M, LR, and MLR groups increased, whereas the pH value and butyric acid, 2,3-butanediol, and ethanol contents decreased compared to those of C group after 7, 14, and 56 d of fermentation. A two-way analysis of variance (ANOVA) was performed to estimate the results. The LR group exhibited increased Lactobacillus abundance, whereas the M and MLR groups showed increased Weissella abundance compared to the C group. The relative contents of amino acids (tyrosine, isoleucine, threonine, arginine, valine, and citrulline) in the M and MLR groups were higher than those in the C group. During fermentation, the M, LR, and MLR groups showed decreased phenylalanine, isoleucine, and ferulic acid contents. Amino acids such as isoleucine and L-aspartic acid were positively correlated with Lactobacillus but negatively correlated with Weissella. In conclusion, combining high-throughput sequencing and liquid chromatography–mass spectrometry during anaerobic alfalfa fermentation can reveal new microbial community compositions and metabolite profiles, supporting the application of M, LR, and MLR as feed fermentation agents.

#1131 Significant reno-cardio-metabolic protection by the food additive Flexovital in a murine model combining unilateral nephrectomy and Western diet

Abstract Background and Aims Cardiovascular complications are major threats in advanced renal failure and metabolic dysfunction with several unmet medical needs. This study aimed to investigate the therapeutic effects of a special food additive (FLEXOVITAL) in a newly developed mouse model of reno-cardio-metabolic disease, induced by moderate renal failure in combination with a special Western diet. Method Male C57BL/6J mice (4 weeks old, n = 18) were subject to unilateral nephrectomy (UNX), fed a Western diet rich in fat carbohydrates and salt (WD), and were followed for 12 weeks compared with SHAM-operated mice on standard chow (n = 19). One group of UNX+WD mice (n = 8) was fed a food additive (FLEXOVITAL; FLX) containing extracts of Rhodiola rosea, beetroot, and the amino acids arginine and citrulline. Body weight (BW), blood pressure (tail-cuff), endothelial-dependent vasorelaxation (myograph), glucose metabolism (IPGTT), body fat and lean mass composition (DEXA), adipocyte area, renal function (Glomerular Filtration Rate (GFR) by plasma clearance of FITC-inulin), and mitochondrial function (Oroboros, High-resolution respirometry) were measured together with biochemical analysis of heart injury (Troponin-I), inflammation (IL6) and histological analyses of the kidney and heart. Results BW gain was seen in the UNX+WD and SHAM group, and was 25% less in the FLX group (p < 0.05). The fat/lean-mass ratio increased by 17% (p < 0.01) and the adipocyte area by 31% (p < 0.001) in the UNX+WD group but was virtually normalized in the FLX group (p < 0.01). Fasting and non-fasting glucose levels became elevated in the UNX+WD group and were reduced in the FLX group (p < 0.05). Impaired glucose clearance in the UNX+WD group, was partially prevented by FLX. BP significantly increased in the UNX+WD group (MAP = 78 → 90 mmHg, p < 0.001), and was largely prevented by FLX (MAP = 82 mmHg, p < 0.01). Endothelial function was significantly impaired in the UNX+WD group (p < 0.01) and partially preserved in the FLX group (p < 0.05). GFR was reduced by almost 60% in the UNX+WD group but improved with a 75% protective effect in the FLX group (p < 0.05). Significant glomerular injuries with mesangial proliferation were observed in the UNX+WD group (p < 0.001) but were less pronounced in the FLX group (p < 0.01). Tubular injury score (1-10) increased from 1 in SHAM to 6.5 in the UNX+WD group and was partly protected (4.5) in the FLX group (p < 0.05). Troponin-I levels were 15 pg/ml in the SHAM group, markedly increased in the UNX+WD group (p < 0.001), whereas completely reversed in the FLX group (p < 0.01). No significant histological cardiac injuries or deviations could be demonstrated. Inflammatory activity (IL6) increased by 88% in the UNX+WD there was a trend of reduction in mice with FLX. Mitochondrial oxygen efficiency (P/O ratio) was improved in the kidneys of the FLX group compared to the UNX+WD group (p < 0.05). Conclusion In the present multiorgan disease model, significant renal, cardiovascular, and metabolic dysfunction/injuries emerge in mice with a moderate reduction of renal function when fed a Western diet rich in fat, carbohydrates, and salt. Protective effects were noted by dietary FLX treatment in most functional assessments made in the model. This indicates FLX is a potential new treatment in patients with reno-cardio-metabolic disease. The next phase involves confirming these findings in the clinical setting.

Paediatric clinical study of 3D printed personalised medicines for rare metabolic disorders

Rare diseases are infrequent, but together they affect up to 6–10 % of the world’s population, mainly children. Patients require precise doses and strict adherence to avoid metabolic or cardiac failure in some cases, which cannot be addressed in a reliable way using pharmaceutical compounding. 3D printing (3DP) is a disruptive technology that allows the real-time personalization of the dose and the modulation of the dosage form to adapt the medicine to the therapeutic needs of each patient. 3D printed chewable medicines containing amino acids (citrulline, isoleucine, valine, and isoleucine and valine combinations) were prepared in a hospital setting, and the efficacy and acceptability were evaluated in comparison to conventional compounded medicines in six children. The inclusion of new flavours (lemon, vanilla and peach) to obtain more information on patient preferences and the implementation of a mobile app to obtain patient feedback in real-time was also used. The 3D printed medicines controlled amino acid levels within target levels as well as the conventional medicines. The deviation of citrulline levels was narrower and closer within the target concentration with the chewable formulations. According to participants’ responses, the chewable formulations were well accepted and can improve adherence and quality of life. For the first time, 3DP enabled two actives to be combined in the same formulation, reducing the number of administrations. This study demonstrated the benefits of preparing 3D printed personalized treatments for children diagnosed with rare metabolic disorders using a novel technology in real clinical practice.

Development of a Two-Dimensional Liquid Chromatographic Method for Analysis of Urea Cycle Amino Acids.

The urea cycle has been found to be closely associated with certain types of cancers and other diseases such as cardiovascular disease and chronic kidney disease. An analytical method for the precise quantification of urea cycle amino acids (arginine, ornithine, citrulline, and argininosuccinate) by off-line two-dimensional liquid chromatography (2D-LC) combined with fluorescence-based detection was developed. Before analysis, the amino acids were derivatised with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) to obtain NBD-amino acids. The first dimension involved the reversed-phase separation, in which NBD derivatives of urea cycle amino acids were completely separated from each other and mostly separated from the 18 NBD-proteinogenic amino acids. The samples were eluted with stepwise gradient using 0.02% trifluoroacetic acid in water-acetonitrile as the mobile phase. In the second dimension, an amino column was used for the separation of NBD-ornithine, -citrulline, and -argininosuccinate, while a sulfonic acid column was used to separate NBD-arginine. The developed 2D-LC system was used to analyse human plasma samples. The fractions of NBD-urea cycle amino acids obtained in the first dimension were collected manually and introduced into the second dimension. By choosing appropriate mobile phases for the second dimension, each NBD-urea cycle amino acid eluted in the first dimension was well separated from the other proteinogenic amino acids and interference from endogenous substance. This could not be achieved in the first dimension. The urea cycle amino acids in human plasma sample were quantified, and the method was well validated. The calibration curves for each NBD-urea cycle amino acid showed good linearity from 3 (ASA) or 15 (Orn, Cit, and Arg) to 600 nM, with correlation coefficients higher than 0.9969. The intraday and interday precisions were less than 7.9% and 15%, respectively. The 2D-LC system is expected to be useful for understanding the involvement of the urea cycle in disease progression.

Plasma arginine levels in arginase deficiency in the “real world”

BackgroundDeficiency of arginase-1, the final enzyme in the urea cycle, causes a distinct clinical syndrome and is characterized biochemically by a high level of plasma arginine. While conventional therapy for urea cycle disorders can lower these levels to some extent, it does not normalize them. Until now, research on plasma arginine levels in this disorder has primarily relied on data from specialized tertiary centers, which limits the ability to assess the natural history and treatment efficacy of arginase-1 deficiency due to the small number of patients in each center and technical variations in plasma arginine measurements among different laboratories. MethodIn this study, we reported plasma arginine levels from 51 patients with arginase-1 deficiency in the database of Quest Diagnostics. The samples were collected from different US regions. ResultsThe mean plasma arginine level in these treated patients was 373 μmol/L and the median level was 368.4 μmol/L. Our data set from 30 arginase deficiency patients with plasma amino acid data from five or more collections revealed significant correlations between the levels of arginine and five other amino acids (citrulline, alanine, ornithine, glutamine, and asparagine). ConclusionDespite treatment, the arginine levels remained persistently elevated and did not change significantly with age, suggesting the current treatment regimen is inadequate to control arginine levels and underscoring the need to seek more effective treatments for this disorder.

Deimination in epidermal barrier and hair formation.

Peptidylarginine deiminases (PADs) transform a protein arginine residue into the non-standard amino acid citrulline. This calcium-dependent post-translational modification of proteins is called citrullination or deimination. As described in this special issue, PADs play a role in various physiological processes, and PAD deregulations are involved in many human diseases. Three PADs are expressed in the epidermis, where their roles begin to be deciphered. PAD1 and PAD3 are involved in keratinocyte differentiation, particularly in the epidermal barrier function, keratins, filaggrin and filaggrin-related proteins being the most abundant deiminated epidermal proteins. Reduced amounts of deiminated proteins and PAD1 expression may be involved in the pathogenesis of psoriasis and atopic dermatitis, two very frequent and chronic skin inflammatory diseases. The trichohyalin/PAD3/transglutaminase three pathway is important for hair shaft formation. Mutations of the PADI3 gene, leading to a decreased activity or abnormal localization of the corresponding isotype, are the cause of a rare hair disorder called uncombable hair syndrome, and are associated with the central centrifugal cicatricial alopecia, a frequent alopecia mainly affecting women of African ancestry. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.

Ornithine is the central intermediate in the arginine degradative pathway and its regulation in Bacillus subtilis

The Gram-positive bacterium Bacillus subtilis can utilize several proteinogenic and non-proteinogenic amino acids as sources of carbon, nitrogen, and energy. The utilization of the amino acids arginine, citrulline, and ornithine is catalyzed by enzymes encoded in the rocABC and rocDEF operons and by the rocG gene. The expression of these genes is controlled by the alternative sigma factor SigL. RNA polymerase associated with this sigma factor depends on ATP-hydrolyzing transcription activators to initiate transcription. The RocR protein acts as a transcription activator for the roc genes. However, the details of amino acid metabolism via this pathway are unknown. Here, we investigated the contributions of all enzymes of the Roc pathway to the degradation of arginine, citrulline, and ornithine. We identified the previously uncharacterized RocB protein as responsible for the conversion of citrulline to ornithine. Invitro assays with the purified enzyme suggest that RocB acts as a manganese-dependent N-carbamoyl-L-ornithine hydrolase that cleaves citrulline to form ornithine and carbamate. Moreover, the molecular effector that triggers transcription activation by RocR has not been unequivocally identified. Using a combination of transcription reporter assays and biochemical experiments, we demonstrate that ornithine is the molecular inducer of RocR activity. Taken together, our work suggests that binding of ATP to RocR triggers its hexamerization, and binding of ornithine then allows ATP hydrolysis and activation of roc gene transcription. Thus, ornithine is the central molecule of the roc degradative pathway as it is the common intermediate of arginine and citrulline degradation and the molecular effector of RocR.

PENGARUH WAKTU PEMANASAN TERHADAP KADAR PROKSIMAT, ASAM AMINO SITRULIN DAN SIFAT ORGANOLEPTIKSELAI ALBEDO KULIT SEMANGKA

The watermelon rind contained 60% higher citrulline than the watermelon rind albedo. Citrulline has the benefit of lowering blood pressure.This study aimed to determine the effect of heating time of watermelon rind (albedo) on the citrulline amino acids, chemical properties (proximate), and organoleptic properties. This study conducted using a randomized complete block design (RCBD). The treatment wear heating for 35, 40, 45, and 50 minutes. The results showed that heating time had no significant effect on proximate and citrulline levels (p>0.05). The results of the organoleptic test analysis showed that the heating time had a significant effect on liking (<0.05). The results of the analysis of the viscosity test showed that the heating time had a significant effect on the viscosity of the jam (p<0.05). F4 (heating time 50 minutes) is the chosen option with nutritional content per 100 g, namely energy 192.52 Kcal, protein 0.24 g, fat 0.02 g, carbohydrates 47.83 g, water 51.02 g, ash 0 , 08 g, and the amino acid citrulline 96.94 mg.

Selective inhibition of peptidyl-arginine deiminase (PAD): can it control multiple inflammatory disorders as a promising therapeutic strategy?

Peptidyl arginine deiminases (PADs) are a family of post-translational modification enzymes that irreversibly citrullinate (deiminate) arginine residues of protein and convert them to a non-classical amino acid citrulline in the presence of calcium ions. It has five isotypes, such as PAD1, PAD2, PAD3, PAD4, and PAD6, found in mammalian species. It has been suggested that increased PAD expression in various tissues contributes to the development of multiple inflammatory diseases, including rheumatoid arthritis (RA), cancer, diabetes, and neurological disorders. Elevation of PAD enzyme expression depends on several factors like rising intracellular Ca2+ levels, oxidative stress, and proinflammatory cytokines. PAD inhibitors originating from natural or synthetic sources can be used as a novel therapeutic approach concerning inflammatory disorders. Here, we review the pathological role of PAD in several inflammatory disorders, factors that trigger PAD expression, epigenetic role and finally, decipher the therapeutic approach of PAD inhibitors in multiple inflammatory disorders.

Sarcopenia: investigation of metabolic changes and its associated mechanisms

BackgroundSarcopenia is one of the most predominant musculoskeletal diseases of the elderly, defined as age-related progressive and generalized loss of muscle mass with a simultaneous reduction in muscle strength and/or function. Using metabolomics, we aimed to examine the association between sarcopenia and the plasma metabolic profile of sarcopenic patients, measured using a targeted HPLC-MS/MS platform.MethodsPlasma samples from 22 (17 men) hip fracture patients undergoing surgery (8 sarcopenic, age 81.4+6.3, and 14 non-sarcopenic, age 78.4±8.1) were analyzed. T test, fold change, orthogonal partial least squares discriminant analysis, and sparse partial least squares discriminant analysis were used for mining significant features. Metabolite set enrichment analysis and mediation analysis by PLSSEM were thereafter performed.ResultsUsing a univariate analysis for sarcopenia z score, the amino acid citrulline was the only metabolite with a significant group difference after FDR correction. Positive trends were observed between the sarcopenia z score and very long-chain fatty acids as well as dicarboxylic acid carnitines. Multivariate analysis showed citrulline, non-esterified fatty acid 26:2, and decanedioyl carnitine as the top three metabolites according to the variable importance in projection using oPLS-DA and loadings weight by sPLS-DA. Metabolite set enrichment analysis showed carnitine palmitoyltransferase deficiency (II) as the highest condition related to the metabolome.ConclusionsWe observed a difference in the plasma metabolic profile in association with different measures of sarcopenia, which identifies very long-chain fatty acids, Carn.DC and citrulline as key variables associated with the disease severity. These findings point to a potential link between sarcopenia and mitochondrial dysfunction and portraits a number of possible biochemical pathways which might be involved in the disease pathogenesis.

A Metabolomics-Based Investigation of the Effects of a Short-Term Body Weight Reduction Program in a Cohort of Adolescents with Obesity: A Prospective Interventional Clinical Study.

Metabolomics applied to assess the response to a body weight reduction program (BWRP) may generate valuable information concerning the biochemical mechanisms/pathways underlying the BWRP-induced cardiometabolic benefits. The aim of the present study was to establish the BWRP-induced changes in the metabolomic profile that characterizes the obese condition. In particular, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to determine a total of 188 endogenous metabolites in the plasma samples of a cohort of 42 adolescents with obesity (female/male = 32/10; age = 15.94 ± 1.33 year; body mass index standard deviation score (BMI SDS) = 2.96 ± 0.46) who underwent a 3-week BWRP, including hypocaloric diet, physical exercise, nutritional education, and psychological support. The BWRP was capable of significantly improving body composition (e.g., BMI SDS, p < 0.0001), glucometabolic homeostasis (e.g., glucose, p < 0.0001), and cardiovascular function (e.g., diastolic blood pressure, p = 0.016). A total of 64 metabolites were significantly reduced after the intervention (at least p < 0.05), including 53 glycerophospholipids (23 PCs ae, 21 PCs aa, and 9 lysoPCs), 7 amino acids (tyrosine, phenylalanine, arginine, citrulline, tryptophan, glutamic acid, and leucine), the biogenic amine kynurenine, 2 sphingomyelins, and (free) carnitine (C0). On the contrary, three metabolites were significantly increased after the intervention (at least p < 0.05)-in particular, glutamine, trans-4-hydroxyproline, and the octadecenoyl-carnitine (C18:1). In conclusion, when administered to adolescents with obesity, a short-term BWRP is capable of changing the metabolomic profile in the plasma.

Metabolomic Analysis of Microcystis aeruginosa After Exposure to the Algicide L-Lysine.

The widespread occurrence of cyanobacteria blooms damages the water ecosystem and threatens the safety of potable water and human health. Exogenous L-lysine significantly inhibits the growth of a dominant cyanobacteria Microcystis aeruginosa in freshwater. However, the molecular mechanism of how lysine inhibits the growth of M. aeruginosa is unclear. In this study, both non-target and target metabolomic analysis were performed to investigate the effects of algicide L-lysine. The results showed that 8mg L- 1 lysine most likely disrupts the metabolism of amino acids, especially the arginine and proline metabolism. According to targeted amino acid metabolomics analysis, only 3 amino acids (L-arginine, ornithine, and citrulline), which belong to the ornithine-ammonia cycle (OAC) in arginine metabolic pathway, showed elevated levels. The intracellular concentrations of ornithine, citrulline, and arginine increased by 115%, 124%, and 19.4%, respectively. These results indicate that L-lysine may affect arginine metabolism and OAC to inhibit the growth of M. aeruginosa.

Amino acid signature during sickle cell pain crisis shows significant alterations related to nitric oxide and energy metabolism.

Nitric oxide depletion secondary to arginase induced arginine deficiency has been shown to be important in the pathophysiology of vaso-occlusion in sickle cell pain crisis. Our objective of this study was to perform a comprehensive amino acid evaluation during sickle cell pain crisis. In a total of 58 subjects (29 in steady-state sickle cell disease and 29 with sickle cell pain crisis), the amino acids related to nitric oxide pathway was significantly decreased during sickle cell pain crisis compared to steady-state sickle cell disease: arginine (p = 0.001), citrulline (p = 0.012), and ornithine (p = 0.03). In addition, the amino acids related to energy metabolism was significantly decreased during a pain crisis: asparagine (p < 0.001), serine (p = 0.002), histidine (p = 0.017), alanine (p = 0.004), tyrosine (p = 0.012), methionine (p = 0.007), cystine (p = 0.016), isoleucine (p = 0.016) and lysine (p = 0.006). The amino acid related to oxidative stress were significantly higher during a sickle cell pain crisis (glutamic acid (p < 0.001). Furthermore, multivariate analysis with partial least squares-discriminant analysis (PLS-DA) showed that deficiencies of the amino acids arginine, asparagine, citrulline, methionine and alanine were the most important related to sickle cell pain crisis.