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1.
Protein Solvent Interaction: Transition of Protein-solvent Interaction Concept from Basic Research into Solvent Manipulation of Chromatography.
Arakawa, T, Kita, Y
Current protein & peptide science. 2019;(1):34-39
Abstract
Previously, we have reviewed in this journal (Arakawa, T., Kita, Y., Curr. Protein Pept. Sci., 15, 608-620, 2014) the interaction of arginine with proteins and various applications of this solvent additive in the area of protein formulations and downstream processes. In this special issue, we expand the concept of protein-solvent interaction into the analysis of the effects of solvent additives on various column chromatography, including mixed-mode chromatography. Earlier in our research, we have studied the interactions of such a variety of solvent additives as sugars, salts, amino acids, polymers and organic solvents with a variety of proteins, which resulted in mechanistic understanding on their protein stabilization and precipitation effects, the latter known as Hofmeister series. While such a study was then a pure academic research, rapid development of genetic engineering technologies and resultant biotechnologies made it a valuable knowledge in fully utilizing solvent additives in manipulation of protein solution, including column chromatography.
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2.
Exceptionally versatile - arginine in bacterial post-translational protein modifications.
Lassak, J, Koller, F, Krafczyk, R, Volkwein, W
Biological chemistry. 2019;(11):1397-1427
Abstract
Post-translational modifications (PTM) are the evolutionary solution to challenge and extend the boundaries of genetically predetermined proteomic diversity. As PTMs are highly dynamic, they also hold an enormous regulatory potential. It is therefore not surprising that out of the 20 proteinogenic amino acids, 15 can be post-translationally modified. Even the relatively inert guanidino group of arginine is subject to a multitude of mostly enzyme mediated chemical changes. The resulting alterations can have a major influence on protein function. In this review, we will discuss how bacteria control their cellular processes and develop pathogenicity based on post-translational protein-arginine modifications.
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3.
Evaluation of kinetic data: What the numbers tell us about PRMTs.
Frankel, A, Brown, JI
Biochimica et biophysica acta. Proteins and proteomics. 2019;(3):306-316
Abstract
Protein arginine N-methyltransferase (PRMT) kinetic parameters have been catalogued over the past fifteen years for eight of the nine mammalian enzyme family members. Like the majority of methyltransferases, these enzymes employ the highly ubiquitous cofactor S-adenosyl-l-methionine as a co-substrate to methylate arginine residues in peptidic substrates with an approximately 4-μM median KM. The median values for PRMT turnover number (kcat) and catalytic efficiency (kcat/KM) are 0.0051 s-1 and 708 M-1 s-1, respectively. When comparing PRMT metrics to entries found in the BRENDA database, we find that while PRMTs exhibit high substrate affinity relative to other enzyme-substrate pairs, PRMTs display largely lower kcat and kcat/KM values. We observe that kinetic parameters for PRMTs and arginine demethylase activity from dual-functioning lysine demethylases are statistically similar, paralleling what the broader enzyme families in which they belong reveal, and adding to the evidence in support of arginine methylation reversibility.
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4.
The Anticaries Efficacy of a 1.5% Arginine and Fluoride Toothpaste.
Wolff, MS, Schenkel, AB
Advances in dental research. 2018;(1):93-97
Abstract
Dental caries remains a world-wide disease despite the global distribution of fluoride. It has become apparent that the introduction of significant levels of sugar (fermentable carbohydrate) into the diet has resulted in a change in the biofilm, encouraging acid formation. Further, there has been a shift in the microbiota in the biofilm to a flora that produces acid, and thrives and reproduces in an acidic environment. The management of caries activity under these conditions has focused on brushing to remove the biofilm with fluoride pastes, and high-dose fluoride treatments. Kleinberg, in the 1970s, identified an arginine-containing compound in saliva that several oral biofilm bacterial species metabolize to produce base. Multiple in situ and in vivo studies have been conducted, and have discussed the ability of multiple bacteria to increase the resting pH of the biofilm and even reduce the decrease in pH when the biofilm is challenged with glucose. This shift in resting pH can shift the level of caries formation by the biofilm. Here, we present 8 clinical studies, with different clinical designs, measuring different clinical outcomes, for a diverse, world-wide population. Each of these studies demonstrates reductions in caries formation beyond that seen with fluoride alone and several demonstrate the reversal of early caries lesions. Significant clinical research has been shown that 1.5% arginine combined with fluoride toothpaste has superior anti-caries efficacy to toothpaste containing fluoride alone.
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5.
[Enzymatic production of arginine derivatives: a review].
Sun, A, Song, W, Liu, J, Luo, Q, Chen, X, Liu, L
Sheng wu gong cheng xue bao = Chinese journal of biotechnology. 2018;(2):165-176
Abstract
L-arginine (L-Arg) is an alkaline amino acid that possesses various function groups and acts as an important precursor for useful chemical synthesis. L-Arg derivatives are widely applied in pharmaceutical, food and cosmetic industries. Environment friendly and cost-effective production of L-Arg derivatives by enzymatic catalysis provides significant advantages over chemical synthesis and microbial fermentation. In this article, several typical L-Arg derivatives and their enzymatic production processes are highlighted. Furthermore, prospect is also addressed about enzymatic production of L-Arg derivatives.
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6.
Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine.
Morris, CR, Hamilton-Reeves, J, Martindale, RG, Sarav, M, Ochoa Gautier, JB
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2017;(1_suppl):30S-47S
Abstract
Nonessential amino acids are synthesized de novo and therefore not diet dependent. In contrast, essential amino acids must be obtained through nutrition since they cannot be synthesized internally. Several nonessential amino acids may become essential under conditions of stress and catabolic states when the capacity of endogenous amino acid synthesis is exceeded. Arginine and glutamine are 2 such conditionally essential amino acids and are the focus of this review. Low arginine bioavailability plays a pivotal role in the pathogenesis of a growing number of varied diseases, including sickle cell disease, thalassemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, certain cancers, and trauma, among others. Catabolism of arginine by arginase enzymes is the most common cause of an acquired arginine deficiency syndrome, frequently contributing to endothelial dysfunction and/or T-cell dysfunction, depending on the clinical scenario and disease state. Glutamine, an arginine precursor, is one of the most abundant amino acids in the body and, like arginine, becomes deficient in several conditions of stress, including critical illness, trauma, infection, cancer, and gastrointestinal disorders. At-risk populations are discussed together with therapeutic options that target these specific acquired amino acid deficiencies.
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7.
Drug-induced amino acid deprivation as strategy for cancer therapy.
Fung, MKL, Chan, GC
Journal of hematology & oncology. 2017;(1):144
Abstract
Cancer is caused by uncontrollable growth of neoplastic cells, leading to invasion of adjacent and distant tissues resulting in death. Cancer cells have specific nutrient(s) auxotrophy and have a much higher nutrient demand compared to normal tissues. Therefore, different metabolic inhibitors or nutrient-depleting enzymes have been tested for their anti-cancer activities. We review recent available laboratory and clinical data on using various specific amino acid metabolic pathways inhibitors in treating cancers. Our focus is on glutamine, asparagine, and arginine starvation. These three amino acids are chosen due to their better scientific evidence compared to other related approaches in cancer treatment. Amino acid-specific depleting enzymes have been adopted in different standard chemotherapy protocols. Glutamine starvation by glutaminase inhibitior, transporter inhibitor, or glutamine depletion has shown to have significant anti-cancer effect in pre-clinical studies. Currently, glutaminase inhibitor is under clinical trial for testing anti-cancer efficacy. Clinical data suggests that asparagine depletion is effective in treating hematologic malignancies even as a single agent. On the other hand, arginine depletion has lower toxicity profile and can effectively reduce the level of pro-cancer biochemicals in patients as shown by ours and others' data. This supports the clinical use of arginine depletion as anti-cancer therapy but its exact efficacy in various cancers requires further investigation. However, clinical application of these enzymes is usually hindered by common problems including allergy to these foreign proteins, off-target cytotoxicity, short half-life and rapidly emerging chemoresistance. There have been efforts to overcome these problems by modifying the drugs in different ways to circumvent these hindrance such as (1) isolate human native enzymes to reduce allergy, (2) isolate enzyme isoforms with higher specificities and efficiencies, (3) pegylate the enzymes to reduce allergy and prolong the half-lives, and (4) design drug combinations protocols to enhance the efficacy of chemotherapy by drug synergy and minimizing resistance. These improvements can potentially lead to the development of more effective anti-cancer treatment with less adverse effects and higher therapeutic efficacy.
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8.
Efficacy of a Disease-Specific Nutritional Support for Pressure Ulcer Healing: A Systematic Review and Meta-Analysis.
Cereda, E, Neyens, JCL, Caccialanza, R, Rondanelli, M, Schols, JMGA
The journal of nutrition, health & aging. 2017;(6):655-661
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Abstract
OBJECTIVES The aim of this systematic review was to summarize the evidence on the efficacy of high-calorie, high-protein nutritional formula enriched with arginine, zinc, and antioxidants (disease-specific support) in patients with pressure ulcers (PUs). METHODS Randomized controlled trials in English published from January 1997 until October 2015 were searched for in electronic databases (EMBASE, Medline, PubMed, and CINAHL). Studies comparing a disease-specific nutritional support (oral supplements or tube feeding) to a control nutritional intervention enabling the satisfaction of energy requirements regardless of the use of high-calorie formula or placebo or no support for at least 4 weeks were considered eligible. Study outcomes were the percentage of change in PU area, complete healing and reduction in the PU area ≥40% at 8 weeks, and the percentage of change in area at 4 weeks. RESULTS A total of 3 studies could be included in the meta-analysis. Compared with control interventions, formulas enriched with arginine, zinc and antioxidants resulted in significantly higher reduction in ulcer area (-15.7% [95%CI, -29.9, -1.5]; P=0.030; I2=58.6%) and a higher proportion of participants having a 40% or greater reduction in PU size (OR=1.72 [95%CI, 1.04, 2.84]; P=0.033; I2=0.0%) at 8 weeks. A nearly significant difference in complete healing at 8 weeks (OR=1.72 [95%CI, 0.86, 3.45]; P=0.127; I2=0.0%) and the percentage of change in the area at 4 weeks (-7.1% [95%CI, -17.4, 3.3]; P=0.180; I2=0.0%) was also observed. CONCLUSIONS This systematic review shows that the use of formulas enriched with arginine, zinc and antioxidants as oral supplements and tube feeds for at least 8 weeks are associated with improved PU healing compared with standard formulas.
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Review of the endothelial pathogenic mechanism of TIE2-related venous malformation.
Du, Z, Zheng, J, Zhang, Z, Wang, Y
Journal of vascular surgery. Venous and lymphatic disorders. 2017;(5):740-748
Abstract
BACKGROUND Venous malformation (VM) is a type of disease involving vascular morphogenesis in humans. Clinically, VM can be sporadic or inherited. TIE2, also known as TEK or HYK, is a member of the receptor tyrosine kinase subfamily and is highly conserved among species. In 1996, an arginine-to-tryptophan substitution at position 849 (R849W) in TIE2 was found to induce hereditary VM. Additional alterations in TIE2 involved in the pathogenesis of inherited or sporadic VM have since been reported. METHODS The relevant key literature was selectively reviewed, including case reports, reviews, research studies, and meta-analyses. RESULTS TIE2 can be thought of as the basis for VM, with a potential role in determining locations, through intracorporal endothelium-specific distribution and expression from the embryonic phase. It has a sophisticated protein structure, and various point mutations destroy its function and physiologic processes by obviously different activation mechanisms, of which some inhibit dephosphorylation and others maintain phosphorylation. Extracellularly, whereas angiopoietins (ANGs) are ligands of TIE2, the chaotic balance between ANG1 and ANG2 in VM is related to their effects on switching between the cell-cell/cell-extracellular matrix contact conditions and vascular quiescence/angiogenesis state, resulting in corrupted contacts. Intracellularly, among diverse cellular pathways, phosphatidylinositol 4,5-bisphosphate 3-kinase/AKT serine-threonine kinase, mitogen-activated protein kinase, and Dok-related protein are irreplaceable keys underlying changes in endothelial morphology and behavioral biology in VM. For example, R849W and L914F (a leucine-to-phenylalanine substitution at position 914), the most important and frequent TIE2 mutations associated with VM, share similar phenotypes but differ with respect to signaling pathways, heredity, and triggering factors. CONCLUSIONS Based on this comprehensive analysis, we propose an avalanche theory, in which mutant TIE2 is a trigger and pathogenic core, the intercellular network is a tool, altered extracellular matrix and contacts are the final foothold, and fragile contacts are the result. Precise classification according to TIE2 mutation type in VM, especially the mutation site, is important for future targeted therapies.
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10.
The Superior Anti-caries Efficacy of Fluoride Toothpaste Containing 1.5% Arginine.
Cummins, D
The Journal of clinical dentistry. 2016;(2):27-38
Abstract
Innovation in the dental caries area and the development of new superior efficacy treatments to prevent dental caries are as important today as they have ever been, because caries remains a highly prevalent disease globally. Appropriately designed and well-conducted, randomized clinical trials (RCTs) are best-in-class evidence of the effectiveness of a new intervention in medicine and dentistry, and traditional two- to threeyear caries clinical trials are currently the gold standard for proof of superior caries prevention efficacy. Based upon a detailed understanding of plaque metabolism and the importance of pH rise factors in the prevention of caries, a novel toothpaste containing 1.5% arginine, an insoluble calcium compound, and fluoride has been developed, and its superior efficacy compared to toothpaste with fluoride alone has been validated in an unprecedented series of ten RCTs. The results of these RCTs are summarized, and some of the details of the procedures used in the studies are clarified in order to provide an opportunity for objective assessment of their quality. In addition, the results of studies which explored the mechanism of action of this toothpaste are summarized. The arginine-containing fluoride toothpaste offers its users the opportunity to supplement mechanical plaque control with a new technology that helps maintain the natural oral flora in a state that is compatible with health, so as to retain the beneficial effects of the natural flora while significantly reducing the risk of dental caries compared to conventional fluoride toothpaste.