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Impact of prolonged storage on quality assessment properties and constituents of honey: A systematic review

Manickavasagam G, Saaid M, Lim V

J Food Sci, 2024 Feb;89(2):811-833.
PMID: 38224177 DOI: 10.1111/1750-3841.16921

This systematic review paper aims to discuss the trend in quality assessment properties and constituents of honey at different storage conditions and confer the possible whys and wherefores associated with the significant changes. Initially, a literature search was conducted through Google Scholar, ScienceDirect, PubMed, and Scopus databases. In total, 43 manuscripts published between 2001 and 2023 that met the inclusion and exclusion criteria were chosen for the review. As an outcome of this review, prolonged honey storage could deteriorate sensory, nutritional, and antioxidant properties and promote fermentation, granulation, microbial growth, carcinogenicity, organotoxicity, and nephrotoxicity. This systematic review also recognized that diastase activity, invertase activity, 5-hydroxymethylfurfural content, proline content, sugar content, amino acids, and vitamins could be used as indicators to distinguish fresh and stored honey based on the significant test (p-value) in the reported studies. However, all the reported studies used the simplest approach (one-way ANOVA) to identify the significant differences in the analyzed parameter during the storage period and none of them reported an approach to identify the most influential parameter at different storage conditions. In conclusion, orthogonal partial least squares discriminant analysis (supervised multivariate statistical tool) has to be employed in future studies to find the most influential parameter and could be used to potent chemical markers to distinguish fresh and stored honey because this analysis is incorporated with S-plot, variable importance of projection, and one-way ANOVA, which can produce the most accurate and precise results rather solely depending on one-way ANOVA.

Matched MeSH terms: Amino Acids/analysis
Insights into bacterial community metatranscriptome and metabolome in river water influenced by palm oil mill effluent final discharge

Sharuddin SS, Ramli N, Yusoff MZM, Muhammad NAN, Ho LS, Maeda T

J Appl Microbiol, 2023 Oct 04;134(10).
PMID: 37757470 DOI: 10.1093/jambio/lxad219

AIMS: This study aimed to investigate the effect of palm oil mill effluent (POME) final discharge on the active bacterial composition, gene expression, and metabolite profiles in the receiving rivers to establish a foundation for identifying potential biomarkers for monitoring POME pollution in rivers.
METHODS AND RESULTS: The POME final discharge, upstream (unpolluted by POME), and downstream (effluent receiving point) parts of the rivers from two sites were physicochemically characterized. The taxonomic and gene profiles were then evaluated using de novo metatranscriptomics, while the metabolites were detected using qualitative metabolomics. A similar bacterial community structure in the POME final discharge samples from both sites was recorded, but their composition varied. Redundancy analysis showed that several families, particularly Comamonadaceae and Burkholderiaceae [Pr(>F) = 0.028], were positively correlated with biochemical oxygen demand (BOD5) and chemical oxygen demand (COD). The results also showed significant enrichment of genes regulating various metabolisms in the POME-receiving rivers, with methane, carbon fixation pathway, and amino acids among the predominant metabolisms identified (FDR 4, and PPDE > 0.95). This was further validated through qualitative metabolomics, whereby amino acids were detected as the predominant metabolites.
CONCLUSIONS: The results suggest that genes regulating amino acid metabolism have significant potential for developing effective biomonitoring and bioremediation strategies in river water influenced by POME final discharge, fostering a sustainable palm oil industry.

Matched MeSH terms: Amino Acids/metabolism
Need analysis of a dietary application among caregivers of patients with disorders of amino acid metabolism (AAMDs): A mixed-method approach

Lim JY, Ali NM, Rajikan R, Amit N, Hamid HA, Leong HY, et al.

Int J Med Inform, 2023 Sep;177:105120.
PMID: 37295139 DOI: 10.1016/j.ijmedinf.2023.105120

BACKGROUND: A dietary application can assist the caregivers of AAMDs children in auto-calculating the protein intake, hence improving dietary compliance. However, existing dietary application for patients with AAMDs only focus on delivering the nutritional content of food and monitoring the dietary intake but were lacking in other educational components.
OBJECTIVE: To assess the uses, needs and preferences towards a dietary application among the caregivers of AAMDs patients.
METHODS: We conducted a mixed-method study comprising focus group discussion (FGD) and a quantitative questionnaire survey among caregivers of patients aged between 6-month-old to 18-year-old with AAMDs who are receiving active treatment, both medical and dietetic treatment in the genetic clinic, Hospital Kuala Lumpur (HKL).
RESULTS: A total of 76 and 20 caregivers participated in the survey and FGD respectively. All the caregivers (100%) possessed a smartphone and most of the caregivers (89.5%) had the experience of using smartphone or other technological devices to search for health or medical information. However, majority of the participants were not aware of the existence of any web-based or mobile application related to AAMDs (89.5%). While for the qualitative part, three themes emerged: (1) experience with current source of information; (2) needs for supporting self-management educational contents and needs for technological design application. Most of the caregivers used the nutritional booklet as sources of reference but some of them searched for web-based information. Features perceived by the caregivers included a digital food composition database, sharing diet recall with healthcare providers, self-monitoring diet intake as well as low protein recipes. Besides that, user-friendly and ease to use were also perceived as the important features by the caregivers.
CONCLUSION: The identified features and needs by the caregivers should be integrated into the design of the apps to promote acceptance and usage.

Matched MeSH terms: Amino Acids
Metabolite profiling from different parts of tender fruit endosperm of Borassus flabellifer L. (ice apple)

Vasudevan V, Prabaharan J, Krishnan N, K A, Gopinath SCB, Raman P

Anal Methods, 2023 Aug 03;15(30):3735-3751.
PMID: 37493014 DOI: 10.1039/d3ay00704a

Borassus flabellifer L., commonly known as Asian palmyra, is native to South and Southeast Asia. The endosperms of B. flabellifer (known as nungu in Dravidian culture) are widely consumed during the summer season. It is rich in various nutrients and helps in reducing weight, treating skin and digestive issues, lowering body temperature, and managing migraines and diabetes. This study focuses on identifying the small molecules and proteins from the two varieties of B. flabellifer tender fruit endosperms collected from districts around Chennai, Tamil Nadu, India. The collected free nuclear endosperm was subjected to direct extraction and the mesocarp and cellular endosperms were lyophilized and homogenized. Metabolites were extracted by hexane, methanol, and chloroform and investigated using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The compounds identified were from the classes of carboxylic acids, flavonoids, amino acids, alkaloids, fatty acids, oligopeptides, vitamins, and glycosides. High-performance liquid chromatography (HPLC) technique was employed to estimate the quantity of amino acids, wherein the total amino acid in the green variety was found to be higher than in the black variety. Proteins were identified after simulating with a gastrointestinal enzyme using liquid chromatography tandem mass spectrometry (LC-MS/MS)-based peptide mass fingerprinting. The different mineral oxides present in the tender fruit endosperm were identified using X-ray diffraction studies, which confirmed the presence of mineral oxides, such as Br1.25ClO2.75Pb3.88, calcium zirconium tantalum oxide, and barium fluoroniobate. This study validates the presence of bioactive metabolites in green and black varieties of B. flabellifer tender fruit endosperm with a range of activities, such as anti-inflammatory, antibacterial, anticancer, and anti-diabetic properties.

Matched MeSH terms: Amino Acids/metabolism
Biobased natural deep eutectic system as versatile solvents: Structure, interaction and advanced applications

Usmani Z, Sharma M, Tripathi M, Lukk T, Karpichev Y, Gathergood N, et al.

Sci Total Environ, 2023 Jul 10;881:163002.
PMID: 37003333 DOI: 10.1016/j.scitotenv.2023.163002

The increasing emphasis on the development of green replacements to traditional organic solvents and ionic liquids (ILs) can be attributed to the rising concerns over human health and detrimental impacts of conventional solvents towards the environment. A new generation of solvents inspired by nature and extracted from plant bioresources has evolved over the last few years, and are referred to as natural deep eutectic solvents (NADES). NADES are mixtures of natural constituents like sugars, polyalcohols, sugar-based alcohols, amino acids and organic acids. Interest in NADES has exponentially grown over the last eight years, which is evident from an upsurge in the number of research projects undertaken. NADES are highly biocompatible as they can be biosynthesized and metabolized by nearly all living organisms. These solvents pose several noteworthy advantages, such as easy synthesis, tuneable physico-chemical properties, low toxicity, high biodegradability, solute sustainability and stabilization and low melting point. Research on the applicability of NADES in diverse areas is gaining momentum, which includes as - media for chemical and enzymatic reactions; extraction media for essential oils; anti-inflammatory and antimicrobial agent; extraction of bioactive composites; as chromatographic media; preservatives for labile compounds and in drug synthesis. This review gives a complete overview of the properties, biodegradability and toxicity of NADES which we propose can assist in further knowledge generation on their significance in biological systems and usage in green and sustainable chemistry. Information on applications of NADES in biomedical, therapeutic and pharma-biotechnology fields is also highlighted in the current article along with the recent progress and future perspectives in novel applications of NADES.

Matched MeSH terms: Amino Acids
Fulltext Prevalence of DDC genotypes in patients with aromatic L-amino acid decarboxylase (AADC) deficiency and in silico prediction of structural protein changes

Himmelreich N, Bertoldi M, Alfadhel M, Alghamdi MA, Anikster Y, Bao X, et al.

Mol Genet Metab, 2023 Jul;139(3):107624.
PMID: 37348148 DOI: 10.1016/j.ymgme.2023.107624

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive genetic disorder affecting the biosynthesis of dopamine, a precursor of both norepinephrine and epinephrine, and serotonin. Diagnosis is based on the analysis of CSF or plasma metabolites, AADC activity in plasma and genetic testing for variants in the DDC gene. The exact prevalence of AADC deficiency, the number of patients, and the variant and genotype prevalence are not known. Here, we present the DDC variant (n = 143) and genotype (n = 151) prevalence of 348 patients with AADC deficiency, 121 of whom were previously not reported. In addition, we report 26 new DDC variants, classify them according to the ACMG/AMP/ACGS recommendations for pathogenicity and score them based on the predicted structural effect. The splice variant c.714+4A>T, with a founder effect in Taiwan and China, was the most common variant (allele frequency = 32.4%), and c.[714+4A>T];[714+4A>T] was the most common genotype (genotype frequency = 21.3%). Approximately 90% of genotypes had variants classified as pathogenic or likely pathogenic, while 7% had one VUS allele and 3% had two VUS alleles. Only one benign variant was reported. Homozygous and compound heterozygous genotypes were interpreted in terms of AADC protein and categorized as: i) devoid of full-length AADC, ii) bearing one type of AADC homodimeric variant or iii) producing an AADC protein population composed of two homodimeric and one heterodimeric variant. Based on structural features, a score was attributed for all homodimers, and a tentative prediction was advanced for the heterodimer. Almost all AADC protein variants were pathogenic or likely pathogenic.

Matched MeSH terms: Amino Acids/genetics
The effect of alkaline extraction and drying techniques on the physicochemical, structural properties and functionality of rice bran protein concentrates

Abd Rahim FN, Wan Ibadullah WZ, Saari N, Brishti FH, Mustapha NA, Ahmad N, et al.

Int J Biol Macromol, 2023 Jul 01;242(Pt 3):124908.
PMID: 37217045 DOI: 10.1016/j.ijbiomac.2023.124908

Rice bran protein concentrates (RBPC) were extracted using mild alkaline solvents (pH: 8, 9, 10). The physicochemical, thermal, functional, and structural aspects of freeze-drying (FD) and spray-drying (SD) were compared. FD and SD of RBPC had porous and grooved surfaces, with FD having non-collapsed plates and SD being spherical. Alkaline extraction increases FD's protein concentration and browning, whereas SD inhibits browning. According to amino acid profiling, RBPC-FD9's extraction optimizes and preserves amino acids. A tremendous particle size difference was prominent in FD, thermally stable at a minimal maximum of 92 °C. Increased pH extraction gives FD greater exposal surface hydrophobicity and positively relates to denaturation enthalpy. Mild pH extraction and drying significantly impacted solubility, improved emulsion properties, and foaming properties of RBPC as observed in acidic, neutral, and alkaline environments. RBPC-FD9 and RBPC-SD10 extracts exhibit outstanding foaming and emulsion activity in all pH conditions, respectively. Appropriate drying selection, RBPC-FD or SD potentially employed as foaming/emulsifier agent or meat analog.

Matched MeSH terms: Amino Acids
Mechanistic insights into the lignin dissolution behavior in amino acid based deep eutectic solvents

Zhang Y, Ren H, Li B, Udin SM, Maarof H, Zhou W, et al.

Int J Biol Macromol, 2023 Jul 01;242(Pt 2):124829.
PMID: 37210053 DOI: 10.1016/j.ijbiomac.2023.124829

Deep eutectic solvents (DESs) composed by amino acids (L-arginine, L-proline, L-alanine) as the hydrogen bond acceptors (HBAs) and carboxylic acids (formic acid, acetic acid, lactic acid, levulinic acid) as hydrogen bond donors (HBDs) were prepared and used for the dissolution of dealkaline lignin (DAL). The mechanism of lignin dissolution in DESs was explored at molecular level by combining the analysis of Kamlet-Taft (K-T) solvatochromic parameters, FTIR spectrum and density functional theory (DFT) calculations of DESs. Firstly, it was found that the formation of new hydrogen bonds between lignin and DESs mainly drove the dissolution of lignin, which were accompanied by the erosion of hydrogen bond networks in both lignin and DESs. The nature of hydrogen bond network within DESs was fundamentally determined by the type and number of functional groups in both HBA and HBD, which affected its ability to form hydrogen bond with lignin. One hydroxyl group and carboxyl group in HBDs provided active protons, which facilitated proton-catalyzed cleavage of β-O-4, thus enhancing the dissolution of DESs. The superfluous functional group resulted in more extensive and stronger hydrogen bond network in the DESs, thus decreasing the lignin dissolving ability. Moreover, it was found that lignin solubility had a closed positive correlation with the subtraction value of α and β (net hydrogen donating ability) of DESs. Among all the investigated DESs, L-alanine/formic acid (1:3) with the strong hydrogen-bond donating ability (acidity), weak hydrogen-bond accepting ability (basicity) and small steric-hindrance effect showed the best lignin dissolving ability (23.99 wt%, 60 °C). On top of that, the value of α and β of L-proline/carboxylic acids DESs showed some positive correlation with the global electrostatic potential (ESP) maxima and minima of the corresponding DESs respectively, indicating the analysis of ESP quantitative distributions of DESs could be an effective tool for DESs screening and design for lignin dissolution as well as other applications.

Matched MeSH terms: Amino Acids
Nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry metabolomics studies on non-organic soybeans versus organic soybeans (Glycine max), and their fermentation by Rhizopus oligosporus

Chong SG, Ismail IS, Ahmad Azam A, Tan SJ, Shaari K, Tan JK

J Sci Food Agric, 2023 Apr;103(6):3146-3156.
PMID: 36426592 DOI: 10.1002/jsfa.12355

BACKGROUND: Soybeans (Glycine max) are high in proteins and isoflavones, which offer many health benefits. It has been suggested that the fermentation process enhances the nutrients in the soybeans. Organic foods are perceived as better than non-organic foods in terms of health benefits, yet little is known about the difference in the phytochemical content that distinguishes the quality of organic soybeans from non-organic soybeans. This study investigated the chemical profiles of non-organic (G, T, U, UB) and organic (C, COF, A, R, B, Z) soybeans (G. max [L.] Merr.) and their metabolite changes after fermentation with Rhizopus oligosporus.
RESULTS: A clear separation was only observed between non-organic G and organic Z, which were then selected for further investigation in the fermentation of soybeans (GF and ZF). All four groups (G, Z, GF, ZF) were analyzed using nuclear magnetic resonance (NMR) spectroscopy along with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this way a total of 41 and 47 metabolites were identified respectively, with 12 in common. A clear variation (|log1.5 FC| > 2 and P amino acids and organic acids were found in ZF. An additional four metabolites clustered as C-glycosylflavonoids were discovered from MS/MS-based molecular networking.
CONCLUSION: Chemical profiles of non-organic and organic soybeans exhibited no significant difference. However, the metabolite profile of the unfermented soybeans, which were higher in sugars, shifted to higher amino acid and organic acid content after fermentation, thereby potentially enhancing their nutritional value. © 2022 Society of Chemical Industry.

Matched MeSH terms: Amino Acids/analysis
Centella asiatica (L.) Urb. Extract ameliorates branched-chain amino acid (BCAA) metabolism in acute reserpine-induced stress zebrafish model via 1H Nuclear Magnetic Resonance (NMR)-based metabolomics approach

Zakaria F, Akhtar MT, Wan Norhamidah WI, Noraini AB, Muhamad A, Shohaimi S, et al.

Comp Biochem Physiol C Toxicol Pharmacol, 2023 Feb;264:109501.
PMID: 36336330 DOI: 10.1016/j.cbpc.2022.109501

Depression is a common mental disorder that can adversely affect psychosocial function and quality of life. However, the exact aetiology and pathogenesis of depression are still unclear. Stress plays a major role in the pathogenesis of depression. The use of currently prescribed antidepressants has many side effects. Centella asiatica (C. asiatica) has shown promising antidepressant activity in rodent models. Here, we developed a reserpine-induced zebrafish stress-like model and performed behavioural analysis, cortisol measurement and 1H-Nuclear Magnetic Resonance (1H NMR) spectroscopy-based metabolomics analysis to test the anti-stress activity of ethanolic extract of C. asiatica (RECA). A significant increase in total distance travelled (F(8,8) = 8.905, p = 0.0054) and a reduction in freezing duration (F(9, 9) = 10.38, p = 0.0018) were found in the open field test (OFT). Asiaticoside, one of tested C.asiatica's triterpenoid gives a significant increase in contact duration (F(5,5) = 142.3, (p = 0.0330) at 2.5 mg/kg). Eight biomarkers were found, i.e. ß-hydroxyisovaleric acid, leucine, threonine, scylloinositol, lactate, betaine, valine, choline and l-fucose, to be responsible for the class separation between stress and RECA-treated groups. Metabolic pathway alteration in zebrafish brain upon treatment with RECA was identified as valine, leucine and isoleucine biosynthesis, while alanine, aspartate, glutamate and glycerophospholipid metabolism was involved after fluoxetine treatment.

Matched MeSH terms: Amino Acids, Branched-Chain
Inhibitory influence of amino acids on the formation kinetics of methane hydrates in oil-water and oil-brine systems

Almashwali AA, Khan MS, Lal B, Jin QC, Sabil KM, Khor SF

Chemosphere, 2023 Jan;312(Pt 2):137325.
PMID: 36423723 DOI: 10.1016/j.chemosphere.2022.137325

This experimental study evaluates the inhibition performance of kinetic hydrates inhibitors (KHIs) of three amino acids, namely: glycine, proline, and alanine. It includes the performance comparison with the conventional inhibitor i.e., polyvinyl pyrrolidine (PVP) on methane (CH4) hydrate in oil systems in two different systems, i.e., deionized and brine water systems. The experiments were conducted in a high-pressure hydrate reactor replicating subsea pipeline conditions, i.e., the temperature of 274 K, pressure 8 MPa, and concentration of 1 wt%, by applying the isochoric cooling technique. The formation kinetics results suggest that all the studied amino acids effectively worked as kinetic inhibitors by potentially delaying CH4 hydrate formations due to their steric hindrance abilities. The interesting phenomenon was observed that the different studied amino acids behave differently in the brine-oil and deionized water-oil systems due to their side chain interaction. In a deionized water-oil system, glycine gives the highest inhibition performance by reducing the hydrate formation risk. On the contrary, in the brine-oil system, proline showed a significant inhibition effect. It should be noted that both glycine and proline were giving almost similar inhibition performance compared to the conventional hydrate inhibitor PVP, however glycine and proline significantly reduced CH4 consumption into hydrate due to their high surface active under CH4 conditions, which strengths the surface tension of the liquid/CH4 interface. Furthermore, according to the findings, it shows that increased side alkyl chain lengths of amino acids increase the efficacy of their kinetic hydration inhibition performance due to better surface adsorption abilities. The amino acids' ability to suppress growth is also linked strongly with hydrophobicity and alkyl side chain length. The findings of this study contribute significantly to current efforts to limit gas hydrate formation in offshore pipelines, particularly in oil-dominant pipelines.

Matched MeSH terms: Amino Acids*
tLyp-1: A peptide suitable to target NRP-1 receptor

Larue L, Kenzhebayeva B, Al-Thiabat MG, Jouan-Hureaux V, Mohd-Gazzali A, Wahab HA, et al.

Bioorg Chem, 2023 Jan;130:106200.
PMID: 36332316 DOI: 10.1016/j.bioorg.2022.106200

Targeting vascular endothelial growth factor receptor (VEFGR) and its co-receptor neuropilin-1 (NRP-1) is an interesting vascular strategy. tLyp-1 is a tumor-homing and penetrating peptide of 7 amino acids (CGNKRTR). It is a truncated form of Lyp-1 (CGNKRTRGC), which is known to target NRP-1 receptor, with high affinity and specificity. It is mediated by endocytosis via C-end rule (CendR) internalization pathway. The aim of this study is to evaluate the importance of each amino acid in the tLyp-1 sequence through alanine-scanning (Ala-scan) technique, during which each of the amino acid in the sequence was systematically replaced by alanine to produce 7 different analogues. In silico approach through molecular docking and molecular dynamics are employed to understand the interaction between the peptide and its analogues with the NRP-1 receptor, followed by in vitro ligand binding assay study. The C-terminal Arg is crucial in the interaction of tLyp-1 with NRP-1 receptor. Substituting this residue dramatically reduces the affinity of this peptide which is clearly seen in this study. Lys-4 is also important in the interaction, which is confirmed via the in vitro study and the MM-PBSA analysis. The finding in this study supports the CendR, in which the presence of R/K-XX-R/K motif is essential in the binding of a ligand with NRP-1 receptor. This presented work will serve as a guide in the future work pertaining the development of active targeting agent towards NRP-1 receptor.

Matched MeSH terms: Amino Acids
Progress in Electrochemical Sensing of Heavy Metals Based on Amino Acids and Its Composites

Tang LW, Alias Y, Zakaria R, Woi PM

Crit Rev Anal Chem, 2023;53(4):869-886.
PMID: 34672838 DOI: 10.1080/10408347.2021.1989657

A detailed overview toward the advancement of amino acid-based electrochemical sensors on the detection of heavy metals is presented. Discussion is focused on the unique properties of various amino acids (AAs) and its composites which allow them being employed in a diverse range of sensing platforms. Formation of metal-ligand complexes in between metal ions and different AAs has been discussed. The essential insights on the interaction between amino acid-based sensors and target heavy metal ions (HMIs) are provided, along with the discussion on their pros and cons. Voltammetry analysis of metal ions based on various interfaces of electrochemical sensors has been highlighted, together with the incorporation of AAs with organic, inorganic and bio-materials. In all these cases, the amino acid modified electrodes have demonstrated large active surface area with abundant adsorption sites for HMIs. The developed sensors are promising for environmental applications, as evidenced by the high selectivity, high sensitivity, high catalytic activity, and low detection limits. The materials involved, fabrication techniques and its sensing mechanism were comprehensively discussed, and the future outlooks of electrochemical sensing platforms are emphasized in this review.

Matched MeSH terms: Amino Acids*
Fulltext Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children

Dashti M, Nizam R, Jacob S, Al-Kandari H, Al Ozairi E, Thanaraj TA, et al.

Front Immunol, 2023;14:1238269.
PMID: 37638053 DOI: 10.3389/fimmu.2023.1238269

Type 1 diabetes (T1D) is a complex autoimmune disorder that is highly prevalent globally. The interactions between genetic and environmental factors may trigger T1D in susceptible individuals. HLA genes play a significant role in T1D pathogenesis, and specific haplotypes are associated with an increased risk of developing the disease. Identifying risk haplotypes can greatly improve the genetic scoring for early diagnosis of T1D in difficult to rank subgroups. This study employed next-generation sequencing to evaluate the association between HLA class II alleles, haplotypes, and amino acids and T1D, by recruiting 95 children with T1D and 150 controls in the Kuwaiti population. Significant associations were identified for alleles at the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci, including DRB1*03:01:01, DQA1*05:01:01, and DQB1*02:01:01, which conferred high risk, and DRB1*11:04:01, DQA1*05:05:01, and DQB1*03:01:01, which were protective. The DRB1*03:01:01~DQA1*05:01:01~DQB1*02:01:01 haplotype was most strongly associated with the risk of developing T1D, while DRB1*11:04-DQA1*05:05-DQB1*03:01 was the only haplotype that rendered protection against T1D. We also identified 66 amino acid positions across the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes that were significantly associated with T1D, including novel associations. These results validate and extend our knowledge on the associations between HLA genes and T1D in Kuwaiti children. The identified risk alleles, haplotypes, and amino acid variations may influence disease development through effects on HLA structure and function and may allow early intervention via population-based screening efforts.

Matched MeSH terms: Amino Acids/genetics
Fulltext Probing the substrate binding modes and catalytic mechanisms of BLEG-1, a promiscuous B3 metallo-β-lactamase with glyoxalase II properties

Au SX, Mohd Padzil A, Muhd Noor ND, Matsumura H, Raja Abdul Rahman RNZ, Normi YM

PLoS One, 2023;18(9):e0291012.
PMID: 37672512 DOI: 10.1371/journal.pone.0291012

BLEG-1 from Bacillus lehensis G1 is an evolutionary divergent B3 metallo-β-lactamase (MBL) that exhibited both β-lactamase and glyoxalase II (GLXII) activities. Sequence, phylogeny, biochemical and structural relatedness of BLEG-1 to B3 MBL and GLXII suggested BLEG-1 might be an intermediate in the evolutionary path of B3 MBL from GLXII. The unique active site cavity of BLEG-1 that recognizes both β-lactam antibiotics and S-D-lactoylglutathione (SLG) had been postulated as the key factor for its dual activity. In this study, dynamic ensembles of BLEG-1 and its substrate complexes divulged conformational plasticity and binding modes of structurally distinct substrates to the enzyme, providing better insights into its structure-to-function relationship and enzymatic promiscuity. Our results highlight the flexible nature of the active site pocket of BLEG-1, which is governed by concerted loop motions involving loop7+α3+loop8 and loop12 around the catalytic core, thereby moulding the binding pocket and facilitate interactions of BLEG-1 with both ampicillin and SLG. The distribution of (i) predominantly hydrophobic amino acids in the N-terminal domain, and (ii) flexible amino acids with polar and/or charged side chains in both N- and C-termini provide additional advantages to BLEG-1 in confining the aromatic group of ampicillin, and polar groups of SLG, respectively. The importance of these residues for substrates binding was further confirmed by the reduction in MBL and GLXII activities upon alanine substitutions of Ile-10, Phe-57, Arg-94, Leu-95, and Arg-159. Based on molecular dynamics simulation, mutational, and biochemical data presented herein, the catalytic mechanisms of BLEG-1 toward the hydrolysis of β-lactams and SLG were proposed.

Matched MeSH terms: Amino Acids
Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model

Lützhøft DO, Sinioja T, Christoffersen BØ, Jakobsen RR, Geng D, Ahmad HFB, et al.

BMC Microbiol, 2022 Dec 01;22(1):287.
PMID: 36456963 DOI: 10.1186/s12866-022-02704-w

BACKGROUND: Gut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH.
RESULTS: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.
CONCLUSIONS: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.

Matched MeSH terms: Amino Acids
Fulltext Multipotent Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease: Synthesis, Biological Analysis and Molecular Docking Study of Benzimidazole-Based Thiazole Derivatives

Hussain R, Ullah H, Rahim F, Sarfraz M, Taha M, Iqbal R, et al.

Molecules, 2022 Sep 18;27(18).
PMID: 36144820 DOI: 10.3390/molecules27186087

Twenty-four analogues of benzimidazole-based thiazoles (1-24) were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential. All analogues were found to exhibit good inhibitory potential against cholinesterase enzymes, having IC50 values in the ranges of 0.10 ± 0.05 to 11.10 ± 0.30 µM (for AChE) and 0.20 ± 0.050 µM to 14.20 ± 0.10 µM (for BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Among the series, analogues 16 and 21 were found to be the most potent inhibitors of AChE and BuChE enzymes. The number (s), types, electron-donating or -withdrawing effects and position of the substituent(s) on the both phenyl rings B & C were the primary determinants of the structure-activity relationship (SAR). In order to understand how the most active derivatives interact with the amino acids in the active site of the enzyme, molecular docking studies were conducted. The results obtained supported the experimental data. Additionally, the structures of all newly synthesized compounds were elucidated by using several spectroscopic methods like 13C-NMR, 1H-NMR and HR EIMS.

Matched MeSH terms: Amino Acids
Fulltext The Effect of Intragastric Gavage of High Dose Green Tea Extract on Serum Status of Magnesium, Calcium, and Zinc

Khaleel AK, Shaari RB, Nawi MAA, Al-Yassiri AMH

Asian Pac J Cancer Prev, 2022 Sep 01;23(9):3195-3199.
PMID: 36172684 DOI: 10.31557/APJCP.2022.23.9.3195

OBJECTIVE: Green tea (GT) contains polyphenolic flavonoids, different minerals like magnesium, calcium, and zinc, vitamins, amino acids, carbohydrates, proteins, and others. It has a different health benefit. The aim of the present study was to investigate the effect of intragastric gavage of a high dose GT extract on serum biochemical analysis of magnesium, calcium, and zincin juvenile Wistar albino rats.
METHODS: Twelve rats were used in the study and divided in to two equal groups. All the animals in the control group were intragastically gavaged by distilled water and continues for ten days, from day 24 to day 34 of age, while the animals in the study group were intragastically gavaged by GT extract (300mg/kg/day) which continues also for ten days from day 24 to day 34 of age. On day 34 of age, and two hours after the last dose, the rats were anaesthetized and blood collection by cardiac puncture was taken.
RESULTS: The results showed that the intragastric gavage of a high dose of GT extract caused a non-significant increase in serum magnesium, and calcium levels (p>0.05), but a significant increase in zinc serum level was seen(p< 0.05).
CONCLUSION: GT can cause a significant increase in zinc serum level, and this may explain the significant role of GT in the response to different oxidative stress. It is recommended to measure the Zn serum level in rats after a period longer than two hrs from the time of the last dose of intragastric gavage of GT extract.

Matched MeSH terms: Amino Acids
Fulltext GrAfSS: a webserver for substructure similarity searching and comparisons in the structures of proteins and RNA

Ghani NSA, Emrizal R, Moffit SM, Hamdani HY, Ramlan EI, Firdaus-Raih M

Nucleic Acids Res, 2022 Jul 05;50(W1):W375-W383.
PMID: 35639505 DOI: 10.1093/nar/gkac402

The GrAfSS (Graph theoretical Applications for Substructure Searching) webserver is a platform to search for three-dimensional substructures of: (i) amino acid side chains in protein structures; and (ii) base arrangements in RNA structures. The webserver interfaces the functions of five different graph theoretical algorithms - ASSAM, SPRITE, IMAAAGINE, NASSAM and COGNAC - into a single substructure searching suite. Users will be able to identify whether a three-dimensional (3D) arrangement of interest, such as a ligand binding site or 3D motif, observed in a protein or RNA structure can be found in other structures available in the Protein Data Bank (PDB). The webserver also allows users to determine whether a protein or RNA structure of interest contains substructural arrangements that are similar to known motifs or 3D arrangements. These capabilities allow for the functional annotation of new structures that were either experimentally determined or computationally generated (such as the coordinates generated by AlphaFold2) and can provide further insights into the diversity or conservation of functional mechanisms of structures in the PDB. The computed substructural superpositions are visualized using integrated NGL viewers. The GrAfSS server is available at http://mfrlab.org/grafss/.

Matched MeSH terms: Amino Acids/chemistry
Fulltext A novel sequence-based predictor for identifying and characterizing thermophilic proteins using estimated propensity scores of dipeptides

Charoenkwan P, Chotpatiwetchkul W, Lee VS, Nantasenamat C, Shoombuatong W

Sci Rep, 2021 Dec 10;11(1):23782.
PMID: 34893688 DOI: 10.1038/s41598-021-03293-w

Owing to their ability to maintain a thermodynamically stable fold at extremely high temperatures, thermophilic proteins (TTPs) play a critical role in basic research and a variety of applications in the food industry. As a result, the development of computation models for rapidly and accurately identifying novel TTPs from a large number of uncharacterized protein sequences is desirable. In spite of existing computational models that have already been developed for characterizing thermophilic proteins, their performance and interpretability remain unsatisfactory. We present a novel sequence-based thermophilic protein predictor, termed SCMTPP, for improving model predictability and interpretability. First, an up-to-date and high-quality dataset consisting of 1853 TPPs and 3233 non-TPPs was compiled from published literature. Second, the SCMTPP predictor was created by combining the scoring card method (SCM) with estimated propensity scores of g-gap dipeptides. Benchmarking experiments revealed that SCMTPP had a cross-validation accuracy of 0.883, which was comparable to that of a support vector machine-based predictor (0.906-0.910) and 2-17% higher than that of commonly used machine learning models. Furthermore, SCMTPP outperformed the state-of-the-art approach (ThermoPred) on the independent test dataset, with accuracy and MCC of 0.865 and 0.731, respectively. Finally, the SCMTPP-derived propensity scores were used to elucidate the critical physicochemical properties for protein thermostability enhancement. In terms of interpretability and generalizability, comparative results showed that SCMTPP was effective for identifying and characterizing TPPs. We had implemented the proposed predictor as a user-friendly online web server at http://pmlabstack.pythonanywhere.com/SCMTPP in order to allow easy access to the model. SCMTPP is expected to be a powerful tool for facilitating community-wide efforts to identify TPPs on a large scale and guiding experimental characterization of TPPs.

Matched MeSH terms: Amino Acids

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