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1.
Parahydrogen-Induced Polarization of Amino Acids.
Pravdivtsev, AN, Buntkowsky, G, Duckett, SB, Koptyug, IV, Hövener, JB
Angewandte Chemie (International ed. in English). 2021;(44):23496-23507
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Abstract
Nuclear magnetic resonance (NMR) has become a universal method for biochemical and biomedical studies, including metabolomics, proteomics, and magnetic resonance imaging (MRI). By increasing the signal of selected molecules, the hyperpolarization of nuclear spin has expanded the reach of NMR and MRI even further (e.g. hyperpolarized solid-state NMR and metabolic imaging in vivo). Parahydrogen (pH2 ) offers a fast and cost-efficient way to achieve hyperpolarization, and the last decade has seen extensive advances, including the synthesis of new tracers, catalysts, and transfer methods. The portfolio of hyperpolarized molecules now includes amino acids, which are of great interest for many applications. Here, we provide an overview of the current literature and developments in the hyperpolarization of amino acids and peptides.
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Effects of Micronutrients or Conditional Amino Acids on COVID-19-Related Outcomes: An Evidence Analysis Center Scoping Review.
Rozga, M, Cheng, FW, Moloney, L, Handu, D
Journal of the Academy of Nutrition and Dietetics. 2021;(7):1354-1363
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Abstract
Recent narrative reviews have described the potential efficacy of providing individuals infected with coronavirus disease 2019 (COVID-19) with additional micronutrients to reduce disease severity. Although there are compelling reasons why providing additional micronutrients or conditional amino acids may affect COVID-19-related outcomes, evidence is lacking. The objective of this scoping review is to explore and describe the literature examining the effect of providing additional micronutrients or conditional amino acids (glutamine, arginine) in adults with conditions or infections similar to COVID-19 infection on COVID-19-related health outcomes. A literature search of the MEDLINE database and hand search of Cochrane Database of systematic reviews retrieved 1,423 unique studies, and 8 studies were included in this scoping review. Four studies examined a target population with ventilator-related pneumonia and acute respiratory distress syndrome, and the other 4 studies included patients who were at risk for ventilator-associated pneumonia. Interventions included intravenous ascorbic acid, intramuscular cholecalciferol, enteral and intramuscular vitamin E, enteral zinc sulfate, and oral and parenteral glutamine. In 6 of the 8 included studies, baseline status of the nutrient of interest was not reported and, thus, it is uncertain how outcomes may vary in the context of nutrient deficiency or insufficiency compared with sufficiency. In the absence of direct evidence examining efficacy of providing additional micronutrients or conditional amino acids to standard care, registered dietitian nutritionists must rely on clinical expertise and indirect evidence to guide medical nutrition therapy for patients infected with COVID-19.
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Amino Acid-Induced Impairment of Insulin Signaling and Involvement of G-Protein Coupling Receptor.
Zakaria, NF, Hamid, M, Khayat, ME
Nutrients. 2021;(7)
Abstract
Amino acids are needed for general bodily function and well-being. Despite their importance, augmentation in their serum concentration is closely related to metabolic disorder, insulin resistance (IR), or worse, diabetes mellitus. Essential amino acids such as the branched-chain amino acids (BCAAs) have been heavily studied as a plausible biomarker or even a cause of IR. Although there is a long list of benefits, in subjects with abnormal amino acids profiles, some amino acids are correlated with a higher risk of IR. Metabolic dysfunction, upregulation of the mammalian target of the rapamycin (mTOR) pathway, the gut microbiome, 3-hydroxyisobutyrate, inflammation, and the collusion of G-protein coupled receptors (GPCRs) are among the indicators and causes of metabolic disorders generating from amino acids that contribute to IR and the onset of type 2 diabetes mellitus (T2DM). This review summarizes the current understanding of the true involvement of amino acids with IR. Additionally, the involvement of GPCRs in IR will be further discussed in this review.
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Gluconeogenesis in Plants: A Key Interface between Organic Acid/Amino Acid/Lipid and Sugar Metabolism.
Walker, RP, Chen, ZH, Famiani, F
Molecules (Basel, Switzerland). 2021;(17)
Abstract
Gluconeogenesis is a key interface between organic acid/amino acid/lipid and sugar metabolism. The aims of this article are four-fold. First, to provide a concise overview of plant gluconeogenesis. Second, to emphasise the widespread occurrence of gluconeogenesis and its utilisation in diverse processes. Third, to stress the importance of the vacuolar storage and release of Krebs cycle acids/nitrogenous compounds, and of the role of gluconeogenesis and malic enzyme in this process. Fourth, to outline the contribution of fine control of enzyme activity to the coordinate-regulation of gluconeogenesis and malate metabolism, and the importance of cytosolic pH in this.
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DIOXYGENASE FOR AUXIN OXIDATION 1 catalyzes the oxidation of IAA amino acid conjugates.
Müller, K, Dobrev, PI, Pěnčík, A, Hošek, P, Vondráková, Z, Filepová, R, Malínská, K, Brunoni, F, Helusová, L, Moravec, T, et al
Plant physiology. 2021;(1):103-115
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Abstract
Together with auxin transport, auxin metabolism is a key determinant of auxin signaling output by plant cells. Enzymatic machinery involved in auxin metabolism is subject to regulation based on numerous inputs, including the concentration of auxin itself. Therefore, experiments characterizing altered auxin availability and subsequent changes in auxin metabolism could elucidate the function and regulatory role of individual elements in the auxin metabolic machinery. Here, we studied auxin metabolism in auxin-dependent tobacco BY-2 cells. We revealed that the concentration of N-(2-oxindole-3-acetyl)-l-aspartic acid (oxIAA-Asp), the most abundant auxin metabolite produced in the control culture, dramatically decreased in auxin-starved BY-2 cells. Analysis of the transcriptome and proteome in auxin-starved cells uncovered significant downregulation of all tobacco (Nicotiana tabacum) homologs of Arabidopsis (Arabidopsis thaliana) DIOXYGENASE FOR AUXIN OXIDATION 1 (DAO1), at both transcript and protein levels. Auxin metabolism profiling in BY-2 mutants carrying either siRNA-silenced or CRISPR-Cas9-mutated NtDAO1, as well as in dao1-1 Arabidopsis plants, showed not only the expected lower levels of oxIAA, but also significantly lower abundance of oxIAA-Asp. Finally, ability of DAO1 to oxidize IAA-Asp was confirmed by an enzyme assay in AtDAO1-producing bacterial culture. Our results thus represent direct evidence of DAO1 activity on IAA amino acid conjugates.
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Signatures and Clinical Significance of Amino Acid Flux in Sarcopenia: A Systematic Review and Meta-Analysis.
Dai, M, Lin, T, Yue, J, Dai, L
Frontiers in endocrinology. 2021;:725518
Abstract
BACKGROUND Dysregulation of amino acids is closely linked to the initiation and progression of sarcopenia. We summarized recent advancements in the studies of amino acid profiles in sarcopenia and systematically presented the clinical significance of amino acid flux in sarcopenia. METHODS We systematically searched in MEDLINE, EMBASE, and Cochrane library from inception to June 1, 2021 to capture all studies examining metabolomics of sarcopenia. We used the following keywords: sarcopenia, metabonomics, metabolomics, amino acid profile, and mass spectrometry. Original articles comparing amino acid patterns between persons with and without sarcopenia were included. Two independent investigators independently completed title and abstract screening, data extraction, and quality evaluation. We used a random effects model to examine the association between amino acids levels and sarcopenia. Sensitivity analyses restricted the analyses to studies in which muscle mass was measured by bioelectrical impedance analysis. Study quality was evaluated according to the Agency for Healthcare Research and Quality (AHRQ) checklist. RESULTS The systematic research yielded six eligible articles, comprising 1,120 participants. Five studies used muscle mass in combination with physical performance and/or muscle strength as the criteria to diagnose sarcopenia, while one study used muscle mass as a diagnostic criterion alone. We found that the concentrations of branched-chain amino acids leucine (standardized mean difference [SMD] -1.249; 95% confidence interval [CI]: -2.275, -0.223, P = 0.02, I2 = 97.7%), isoleucine (SMD -1.077; 95% CI: -2.106, -0.049, P = 0.04, I2 = 97.8%), and aromatic amino acid tryptophan (SMD -0.923; 95% CI: -1.580, -0.265, P = 0.01, I2 = 89.9%) were significantly reduced in individuals with sarcopenia. Study results were robust in sensitivity analysis. CONCLUSIONS The homeostasis of amino acids is critical to maintaining muscle health. The profiles of amino acids might be useful biomarkers for the characterization of sarcopenia. Future studies are warranted to study the clinical significance of amino acids in the diagnosis and treatment of sarcopenia.
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Efficacy and safety of Cerebrolysin after futile recanalisation therapy in patients with severe stroke.
Poljakovic, Z, Supe, S, Ljevak, J, Starcevic, K, Peric, I, Blazevic, N, Krbot-Skoric, M, Jovanovic, I, Ozretic, D
Clinical neurology and neurosurgery. 2021;:106767
Abstract
INTRODUCTION Golden standard of acute stroke treatment is recanalisation therapy. However, opening the occluded blood vessel sometimes does not show the expected clinical result or leads to haemorrhagic complications. As neuroinflammation and neurotoxicity play an important role in the pathophysiology of stroke, neuroprotective agents might preserve brain tissue after futile recanalisation. PATIENTS AND METHODS After recanalisation therapy and not later than 24 h after symptoms onset, patients with initial NIHSS of ≥ 8 were assigned to the investigational and control group. The investigational group received intravenous Cerebrolysin as add-on therapy. The primary objective was to assess the clinical efficacy of Cerebrolysin. The secondary objective was to investigate its effect on haemorrhagic transition and to confirm its safety profile. RESULTS Baseline characteristics of patients showed no significant differences between the two groups. No difference could be detected between the two groups in the mRS scale though the Cerebrolysin group showed descriptive superiority over the control group. We found a statistically significant difference considering haemorrhagic transition and mortality rate in favour of the Cerebrolysin group. DISCUSSION The multimodal neurotrophic agent Cerebrolysin holds promise to impact on the late consequences of a reperfusion syndrome. Its influence on reducing neuroinflammation, promoting neuronal cell viability and neurogenesis as well as the stabilising effect on the blood-brain barrier suggests a protective effect on the neurovascular unit even when no recanalisation occurs. We confirmed the excellent safety profile of Cerebrolysin. CONCLUSION Cerebrolysin as add-on therapy might be beneficial and safe for patients with acute stroke in terms of lowering risk for haemorrhagic complications after recanalisation therapy.
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Evaluation of Plasma Free Amino Acid and Carnitine Levels in Patients with Cesarean Scar Pregnancy.
Tammo, O, Uyanikoglu, H, Koyuncu, İ
Combinatorial chemistry & high throughput screening. 2021;(9):1436-1445
Abstract
AIM AND OBJECTIVE This study aimed to explore the plasma free amino acid (FAA) and carnitine levels in pregnant women with cesarean scar pregnancy (CSP), and to compare them with those of healthy pregnant women. MATERIALS AND METHODS This prospective and randomized controlled study was conducted in patients admitted to Harran University Medical Faculty Hospital Obstetrics Clinic between January 2018 and January 2019. A total of 60 patients were included in the study, and the patients were divided into two groups: the CSP group (n = 30) and the healthy pregnant group as the control group (n = 30). The blood samples were taken from the participants between 7 - 12 weeks of gestation. Twenty-seven carnitines and their esters and 14 FAAs were analysed by liquid chromatography - mass spectrometry (LC-MS/MS). RESULTS The mean plasma concentrations of some carnitines, including C2, C5, C5-OH, C5-DC, C6, C8-1, C12, C14, C14-1, C14-2, C16, C16-1, C18, and C18-1 were significantly higher in the CSP group than in the control group. However, other carnitines, including C0, C3, C4, C4-DC, C5- 1, C6-DC, C8, C8-DC, C10, C10-1, C18-1-OH, and C18-2, were similar in both groups. The plasma levels of some FAAs, including Methyl Glutaryl, Leu, Met, Phe, Arg, Orn, and Glu values, were significantly higher in the CSP group than in the control group. However, there was no statistical significance in other FAA levels, including Val, Asa, Tyr, Asp, Ala, Cit, and Gly between the two groups. Additionally, Pearson's correlation analysis showed that there were significantly positive correlations between many FAA and carnitine values. CONCLUSION Since several plasma carnitines and FAA levels were higher in the CSP group than in the control group, we think that scar pregnancy increases the metabolic need for myometrial invasion. Also, we think that these results may be useful in clinical practice for CSP diagnosis.
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Dietary protein and protein substitute requirements in adults with phenylketonuria: A review of the clinical guidelines.
Firman, S, Witard, OC, O'Keeffe, M, Ramachandran, R
Clinical nutrition (Edinburgh, Scotland). 2021;(3):702-709
Abstract
Lifelong dietary treatment is recommended in the management of phenylketonuria (PKU). Accordingly, an increasing adult population require age-specific PKU guidelines on protein requirements to support changing metabolic demands across the lifespan. Given that protein intake for dietary management of PKU is primarily (52-80%) derived from protein substitutes, the prescribing practice of protein substitutes must be underpinned by robust evidence. Whilst dietary guidelines for PKU management is evolving to incorporate adult specific protein recommendations, the scientific evidence underpinning these guidelines is currently limited. Instead, the determination of protein requirements for people with PKU have previously been extrapolated from estimates derived from the general healthy population, based on arguably outdated nitrogen balance methodology. Furthermore, a compensatory factor of 20-40% has been incorporated to account for the reduced uptake and utilisation of the elemental amino acids contained in protein substitutes. However, research informing this compensatory factor has been conducted in younger adults, with the majority of studies in non-PKU individuals. Given extensive evidence that the muscle anabolic response to ingested protein is impaired in older vs. young adults, the validity of current dietary protein recommendations for adults and older adults with PKU has been challenged. This narrative review aims to critically evaluate the existing scientific evidence underpinning current guidelines on protein requirements for adults with PKU, highlighting existing gaps in knowledge and directions for future research. We argue that current guidelines on protein requirements need updating to optimise long-term physical and functional outcomes in older adults with PKU.
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Targeting the Supply Lines of Cancer - A Possible Strategy for Combating the Disease?
Abrahamsen, O, Balslev, E, Høgdall, E
Anticancer research. 2021;(6):2737-2744
Abstract
Cancer cells alter and up-regulate their metabolic activity in order to facilitate the increased demands of malignancy. This leads to an increased need for metabolic "building materials", for example glucose and amino acids. The blood circulation represents the principal supply lines delivering these materials. It, therefore, becomes relevant to investigate if these supply lines - in terms of the concentrations of building materials in the blood - may exhibit a therapeutic window and could be intervened, as they deliver the most basal components required to exert malignant functioning. A key aspect in this strategy is that it targets - in theory - the thermodynamic foundation enabling the activities that, essentially, "make a cancer a cancer". As an initial step, this review examines if the metabolic supply lines carry clinical implications; specifically, if they impact survival and the development of metastases in patients with cancer. Furthermore, it presents and discusses perspectives on potentially targeting these supply lines.