Preparation of a Novel Oat ß-Glucan-Chromium(III) Complex and Its Hypoglycemic Effect and Mechanism.

This study synthesized a novel oat ß-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 104 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.

Oat Beta-Glucan as a Metabolic Regulator in Early Stage of Colorectal Cancer-A Model Study on Azoxymethane-Treated Rats.

Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1ß, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms.

Consumption of Feed Supplemented with Oat Beta-Glucan as a Chemopreventive Agent against Colon Cancerogenesis in Rats.

Colorectal cancer (CRC) accounts for 30% of all cancer cases worldwide and is the second leading cause of cancer-related deaths. CRC develops over a long period of time, and in the early stages, pathological changes can be mitigated through nutritional interventions using bioactive plant compounds. Our study aims to determine the effect of highly purified oat beta-glucan on an animal CRC model. The study was performed on forty-five male Sprague-Dawley rats with azoxymethane-induced early-stage CRC, which consumed feed containing 1% or 3% low molar mass oat beta-glucan (OBG) for 8 weeks. In the large intestine, morphological changes, CRC signaling pathway genes (RT-PCR), and proteins (Western blot, immunohistochemistry) expression were analyzed. Whole blood hematology and blood redox status were also performed. Results indicated that the histologically confirmed CRC condition led to a downregulation of the WNT/ß-catenin pathway, along with alterations in oncogenic and tumor suppressor gene expression. However, OBG significantly modulated these effects, with the 3% OBG showing a more pronounced impact. Furthermore, CRC rats exhibited elevated levels of oxidative stress and antioxidant enzyme activity in the blood, along with decreased white blood cell and lymphocyte counts. Consumption of OBG at any dose normalized these parameters. The minimal effect of OBG in the physiological intestine and the high activity in the pathological condition suggest that OBG is both safe and effective in early-stage CRC.

Isolation, purification and characterization of ß-glucan from cereals - A review.

ß-glucans are soluble fibers found in cereal compounds, including barley, oats etc., as an active component. They are used as a dietary fiber to treat cholesterol, diabetes and cardiovascular diseases. These polysaccharides are important because they can provide many therapeutic benefits related to their biological activity in human like inhibiting tumour growth, anti-inflammatory action, etc. All these activities were usually attached to their molecular weight, structure and degree of branching. The present manuscript reviews the background of ß-glucan, its characterization techniques, the possible ways to extract ß-glucan and mainly focuses on membrane-based purification techniques. The ß-glucan separation methods using polymeric membranes, their operational characteristics, purification methods which may yield pure or crude ß-glucan and structural analysis methods were also discussed. Future direction in research and development related to ß-glucan recovery from cereal were also offered.

In vitro digestibility of starch and protein in cooked wheat and oat whole flours: A comparative study.

Whole grains have garnered significant attention in the food industry due to their retained abundant nutrients when compared to refined grains. However, limited knowledge exists regarding the digestive behavior of starch and protein. This study compared the physicochemical properties and in vitro starch and protein digestibility of cooked whole wheat flour (WF) and naked oat flour (NOF), and evaluated the impact of endogenous components (protein, lipid, ß-glucan, and polyphenol) on the physicochemical properties and digestibility of WF and NOF. The result indicated that the final hydrolysis rate of WF samples (starch: 23.2 %∼46.3 %; protein: 23.1 %∼63.0 %) was lower than that of NOF samples (starch: 32.1 %∼61.0 %; protein: 32.3 %∼63.6 %). The removal of different endogenous components led to improved digestibility of starch and protein in both WF and NOF. This study contributes to the understanding of the starch and protein digestibility of whole grains, consequently facilitating the development of whole grain products.

Impact of temperature and humidity conditions as abiotic stressors on the phytochemical fingerprint of oat (Avena sativa L.) sprouts.

This study aimed to evaluate the effect of temperature (20, 25, and 30 °C) and relative humidity (RH, 50, 55, and 60 %) as abiotic stressors during oat (Avena sativa L.) germination using a 2-level factorial design with central point. UPLC-QToF-MSE identified eighty polyphenols, nine avenanthramides, twelve lignans, and five phytosterols Notably, 100 % germination was achieved at 25 °C/60 % RH from day 3, yielding the longest radicle size. The highest content of most phenolic acids, avenanthramides, and lignans occurred at 30 °C/65 % RH, where 100 % germination was attained by day 5, but with a shorter radicle size. The best flavonoid and phytosterol profle was obtained at 20 °C/55 % RH, achieving only a 67 % germination rate. Therefore, while these conditions enhance the bioactive compound profile, the associate decrease in germination metrics suggests potential distress effects. Consideration of both photochemical outcomes and germination yield is crucial for comprehensive assessments in future applications.

Nutritional and Phytochemical Composition and Associated Health Benefits of Oat (Avena sativa) Grains and Oat-Based Fermented Food Products.

Oats (Avena sativa L.) are a popular functional cereal grain due to their numerous health benefits. This review article summarized the information on the chemical composition and phytonutrients of oats grown in different countries. It also reviewed recently developed fermented oat products to highlight their potential for human health. Oats have an interesting nutritional profile that includes high-quality protein, unsaturated fats, soluble fiber, polyphenolic compounds, and micronutrients. Oat grain has a unique protein composition, with globulins serving as the primary storage protein, in contrast to other cereals, where prolamins are the main storage proteins. Oats have the highest fat content of any cereal, with low saturated fatty acids and high essential unsaturated fatty acid content, which can help reduce the risk of cardiovascular diseases. Oats are a good source of soluble dietary fiber, particularly ß-glucan, which has outstanding functional properties and is extremely important in human nutrition. ß-Glucan has been shown to lower blood cholesterol and glucose absorption in the intestine, thereby preventing diseases such as cardiovascular injury, dyslipidemia, hypertension, inflammatory state, and type 2 diabetes. Oats also contain high concentration of antioxidant compounds. Avenanthramides, which are unique to oats, are powerful antioxidants with high antioxidative activity in humans. Recognizing the nutritional benefits of oats, oat-based fermented food products are gaining popularity as functional foods with high probiotic potential.

Cold Plasma Treatment Increases Bioactive Metabolites in Oat (Avena sativa L.) Sprouts and Enhances In Vitro Osteogenic Activity of their Extracts.

Cold plasma treatment has been studied to enhance the germination, growth, and bioactive phytochemical production in crops. Here, we aimed to investigate the effects of cold plasma treatment on the growth, bioactive metabolite production, and protein expression related to the physiological and osteogenic activities of oat sprouts. Oat seeds were soaked for 12 h, and then exposed to plasma for 6 min/day for 3 days after sowing. Plasma exposure did not significantly change the growth of oat sprouts; however, increased the content of bioactive metabolites. A single exposure for 6 min on the first day (T-1) increased the content of free amino acids (39.4%), γ-aminobutyric acid (53%), and avenacoside B (23%) compared to the control. Hexacosanol content was the highest in T-3 (6 min exposure on each day for 3 days), 28% higher than that in the control. Oat sprout extracts induced the phosphorylation of adenosine 5'-monophosphate-activated protein kinase and osteoblast differentiation was enhanced by increasing the alkaline phosphatase (ALP) activity; all these effects were induced by plasma treatment. Avenacoside B content was positively correlated with ALP activity (r = 0.911, p < 0.1). These results suggest that plasma treatment has the potential to improve the value of oat sprouts and that it may be used in food fortification to enhance nutritional value for promoting human health.

Multi-Bioactivity of Protein Digests and Peptides from Oat (Avena sativa L.) Kernels in the Prevention of the Cardiometabolic Syndrome.

The aim of this study was to characterize the digests and peptides derived from oat kernel proteins in terms of their major enzyme inhibitory activities related to the prevention of cardiometabolic syndrome. It also entailed the characteristics of antioxidant bioactivity of the analyzed material. The study was carried out using coupled in silico and in vitro methods. The additional goal was to investigate whether identified peptides can pervade Caco-2 cells. Based on the results of bioinformatic analysis, it was found that the selected oat proteins may be a potential source of 107 peptides with DPP-IV and/or ACE inhibitory and/or antioxidant activity. The duodenal digest of oat kernels revealed multiple activities. It inhibited the activities of the following enzymes: DPP-IV (IC50 = 0.51 vs. 10.82 mg/mL of the intact protein), α-glucosidase (IC50 = 1.55 vs. 25.20 mg/mL), and ACE (IC50 = 0.82 vs. 34.52 mg/mL). The DPPH• scavenging activity was 35.7% vs. 7.93% that of the intact protein. After in silico digestion of oat proteins, 24 peptides were selected for identification using LC-Q-TOF-MS/MS. Among them, 13 sequences were successfully identified. One of them, i.e., VW peptide, exhibited triple activities, i.e., DPP-IV and ACE inhibitory and DPPH• scavenging activity. The multifunctional peptides: PW, TF, VF, and VW, were identified in the basolateral samples after transport experiments. Both in silico and in vitro analyses demonstrated that oat kernel proteins were the abundant sources of bioactive digests and peptides to be used in a diet for patients suffering from cardiometabolic syndrome.

The Potential Functions and Mechanisms of Oat on Cancer Prevention: A Review.

Oat is classified as a whole grain and contains high contents of protein, lipids, carbohydrates, vitamins, minerals, and phytochemicals (such as polyphenols, flavonoids, and saponins). In recent years, studies have focused on the effects of oat consumption on reducing the risk of a variety of diseases. Reports have indicated that an oat diet exerts certain biological functions, such as preventing cardiovascular diseases, reducing blood glucose, and promoting intestinal health, along with antiallergy, antioxidation, and cancer preventive effects. At present, cancer is the second leading cause of death worldwide. The natural products of oat are an important breakthrough for developing new strategies of cancer prevention, and their ability to interact with multiple cellular targets helps to combat the complexity of cancer pathogenesis. In addition, the comprehensive study of the cancer prevention activity and potential mechanism of oat nutrients and phytochemicals has become a research hotspot. In this Review, we focused on the potential functions of peptides, dietary fiber, and phytochemicals in oats on cancer prevention and further revealed novel mechanisms and prospects for clinical application. These findings might provide a novel approach to deeply understand the functions and mechanisms for cancer prevention of oat consumption.

Structural Analysis and Anti-Inflammatory Effect of a Digalactosyldiacylglycerol-Monoestolide, a Characteristic Glycolipid in Oats.

Digalactosyldiacylglycerol- (DGDG-) monoestolide is a characteristic glycolipid in oats. DGDG-monoestolides possess a unique structure whereby a fatty acid of DGDG is replaced by a fatty acid ester of hydroxy fatty acid (FAHFA). While the physiological effects of DGDG and FAHFA have been reported previously, the effects of DGDG-monoestolides are unknown. Hence, we isolated a major DGDG-monoestolide molecular species from oats, analyzed its structure, and evaluated its anti-inflammatory effect. Based on GC-MS, MS/MS, and NMR analyses, the isolated compound was identified as a DGDG-monoestolide that contains the linoleic acid ester of 15-hydroxy linoleic acid (LAHLA) and linoleic acid (i.e., DGDG-LAHLA). The isolated DGDG-LAHLA was evaluated for its anti-inflammatory effect on LPS-stimulated RAW264 cells. The production of nitric oxide and cytokines (IL-6, TNF-α, and IL-10) were significantly decreased by DGDG-LAHLA, suggesting the anti-inflammatory effect of DGDG-LAHLA for the first time. In addition, our data showed a pronounced uptake of DGDG-LAHLA by cells. Some compounds corresponding to the predicted DGDG-LAHLA metabolites were also detected, suggesting that both intact DGDG-LAHLA and its metabolites may contribute to the above anti-inflammatory activities. These results are expected to expand the availability of oats as a functional food.

Pharmacological and In Silico Analysis of Oat Avenanthramides as EGFR Inhibitors: Effects on EGF-Induced Lung Cancer Cell Growth and Migration.

Avena sativa L. is a wholegrain cereal and an important edible crop. Oats possesses high nutritional and health promoting values and contains high levels of bioactive compounds, including a group of phenolic amides, named avenanthramides (Avns), exerting antioxidant, anti-inflammatory, and anticancer activities. Epidermal growth factor receptor (EGFR) represents one of the most known oncogenes and it is frequently up-regulated or mutated in human cancers. The oncogenic effects of EGFR include enhanced cell growth, angiogenesis, and metastasis, and down-regulation or inhibition of EGFR signaling has therapeutic benefit. Front-line EGFR tyrosine kinase inhibitor therapy is the standard therapy for patients with EGFR-mutated lung cancer. However, the clinical effects of EGFR inhibition may be lost after a few months of treatment due to the onset of resistance. Here, we showed the anticancer activity of Avns, focusing on EGFR activation and signaling pathway. Lung cancer cellular models have been used to evaluate the activity of Avns on tumor growth, migration, EMT, and anoikis induced by EGF. In addition, docking and molecular dynamics simulations showed that the Avns bind with high affinity to a region in the vicinity of αC-helix and the DGF motif of EGFR, jeopardizing the target biological function. Altogether, our results reveal a new pharmacological activity of Avns as EGFR tyrosine kinase inhibitors.

Fiber Preparation from Micronized Oat By-Products: Antioxidant Properties and Interactions between Bioactive Compounds.

This study aimed to investigate the possibility of utilizing oat by-products for fiber preparation. Oat husk (OH) and oat bran (OB) were micronized and used to prepare a novel product rich in fiber and with enhanced antioxidant properties. The basic chemical composition and phenolic acid profile were determined in OH and OB. The antioxidant properties of OH and OB were also analyzed. The type and strength of interactions between the biologically active compounds from their mixtures were characterized by an isobolographic analysis. The analyses showed that the sum of phenolic acids was higher in OH than in OB. Ferulic acid was dominant in both OH and OB; however, its content in OH was over sixfold higher than that in OB. The results also suggested that both OH and OB can be used for preparing fiber with enhanced antioxidant properties. The optimal composition of the preparation, with 60-70% of OH and 30-40% of OB, allows for obtaining a product with 60-70% fiber and enhanced antioxidant activity due to bioactive substances and their synergistic effect. The resulting product can be a valuable additive to various food and dietary supplements.

Inhibition of low-density lipoprotein oxidation, antioxidative and bile acid-binding capacities of hydrolyzed proteins from carbohydrase-treated oat bran.

This study investigated the valorization of oat bran and the use of its proteins to generate polypeptides with antioxidant and bile acid-binding properties. Ten protein hydrolysates were prepared by treating cellulase (CPI) or Viscozyme (VPI) protein isolates with five proteases. VPI-pepsin was the best peroxyl radical scavenger (497 ± 6-µM Trolox equivalents [TE]/g) while VPI-Flavourzyme quenched hydroxyl radicals (28 ± 0.6) and VPI-pepsin superoxide anion radicals (45.3 ± 6.6%). Hydrolysates, except those produced with pepsin, dose-dependently chelated iron whereas VPI-Protamex had the best copper-chelating capacity (59.83 ± 1.40%). These antioxidative capacities were important in preventing by 50% in vitro copper-induced oxidation of human low-density lipoprotein. Furthermore, due to their aromatic amino acid contents and hydrophobicity, the hydrolysates bound up to 46.3% the bile acids taurodeoxycholate and taurocholate. PRACTICAL APPLICATIONS: The presence of oxidants in foods can damage food molecules and decrease their quality. They are also known to increase the risk of developing chronic conditions like cardiovascular disease. Finding new antioxidant molecules are therefore useful in the management of chronic diseases. Data from this work showed that hydrolyzed oat bran proteins can be useful in stabilizing commercial oil as they reduced the oxidation of peanut oil. Additionally, the protein hydrolysates not only prevented the oxidation of linoleic, a common component of both vegetable oils and biological cell membranes, they also inhibited the oxidation of human LDL cholesterol and chelated bile acids. These hydrolysates can then be further explored as multifunctional ingredients for the development of stable functional food products with potential beneficial effects on the cardiovascular system.

An efficient strategy to improve enzymatic hydrolysis of naked oat straw pretreated by Irpex lacteus.

The objective of this study was aiming at developing an efficient strategy to promote enzymatic hydrolysis of naked oat straw and deciphering the potential mechanism. Irpex lacteus and Phlebia acerina were employed to inoculated on the naked oat straw for 4 weeks which the changes of fiber components, fermentation losses, lignin-degrading enzymes production pattern were determined weekly. Furthermore, the 72 h enzymatic hydrolysis of ultimately fermented naked oat straw were also evaluated. The acid detergent lignin was degraded at about 25% along with the moderate dry matter and cellulose loss which both showed selective degradation. The lignin-degrading enzymes production patterns of the two fungi were different which lignin peroxidase was not detected in Irpex lacteus treatment. In addition, the activities of cellulolytic enzymes were higher in Phlebia acerina treatment. After 72 h enzymatic hydrolysis, the reducing sugar content and hydrolysis yield pretreated by Irpex lacteus was 12.92 g/L and 69.49%, respectively. It was much higher than that in sterilized substrate and Phlebia acerina treatment. Meanwhile, the hydrolysis yields of glucose, sum of xylose and arabinose were all improved by Irpex lacteus which were 30.96% and 25.62%, respectively, and showed significant enhancements compared to control and Phlebia acerina treatment. Irpex lacteus is one of effective white rot fungi which could promote the enzymatic hydrolysis of naked oat straw obviously.

Oat Extract Avenanthramide-C Reverses Hippocampal Long-Term Potentiation Decline in Tg2576 Mice.

Memory deterioration in Alzheimer's disease (AD) is thought to be underpinned by aberrant amyloid ß (Aß) accumulation, which contributes to synaptic plasticity impairment. Avenanthramide-C (Avn-C), a polyphenol compound found predominantly in oats, has a range of biological properties. Herein, we performed methanolic extraction of the Avns-rich fraction (Fr. 2) from germinated oats using column chromatography, and examined the effects of Avn-C on synaptic correlates of memory in a mouse model of AD. Avn-C was identified in Fr. 2 based on 1H-NMR analysis. Electrophysiological recordings were performed to examine the effects of Avn-C on the hippocampal long-term potentiation (LTP) in a Tg2576 mouse model of AD. Avn-C from germinated oats restored impaired LTP in Tg2576 mouse hippocampal slices. Furthermore, Avn-C-facilitated LTP was associated with changes in the protein levels of phospho-glycogen synthase kinase-3ß (p-GSK3ß-S9) and cleaved caspase 3, which are involved in Aß-induced synaptic impairment. Our findings suggest that the Avn-C extract from germinated oats may be beneficial for AD-related synaptic plasticity impairment and memory decline.

Comparative Analysis of Machine Learning Methods to Predict Growth of F. sporotrichioides and Production of T-2 and HT-2 Toxins in Treatments with Ethylene-Vinyl Alcohol Films Containing Pure Components of Essential Oils.

The efficacy of ethylene-vinyl alcohol copolymer films (EVOH) incorporating the essential oil components cinnamaldehyde (CINHO), citral (CIT), isoeugenol (IEG), or linalool (LIN) to control growth rate (GR) and production of T-2 and HT-2 toxins by Fusarium sporotrichioides cultured on oat grains under different temperature (28, 20, and 15 °C) and water activity (aw) (0.99 and 0.96) regimes was assayed. GR in controls/treatments usually increased with increasing temperature, regardless of aw, but no significant differences concerning aw were found. Toxin production decreased with increasing temperature. The effectiveness of films to control fungal GR and toxin production was as follows: EVOH-CIT > EVOH-CINHO > EVOH-IEG > EVOH-LIN. With few exceptions, effective doses of EVOH-CIT, EVOH-CINHO, and EVOH-IEG films to reduce/inhibit GR by 50%, 90%, and 100% (ED50, ED90, and ED100) ranged from 515 to 3330 µg/culture in Petri dish (25 g oat grains) depending on film type, aw, and temperature. ED90 and ED100 of EVOH-LIN were >3330 µg/fungal culture. The potential of several machine learning (ML) methods to predict F. sporotrichioides GR and T-2 and HT-2 toxin production under the assayed conditions was comparatively analyzed. XGBoost and random forest attained the best performance, support vector machine and neural network ranked third or fourth depending on the output, while multiple linear regression proved to be the worst.

Immunonutritional Protease Inhibitors from T. durum and A. sativa Display Metabolic Similarities When Assayed on Human Macrophage-like Cells.

This study evaluated the immunonutritional effects caused by protease inhibitors from Avena sativa and Triticum durum to human macrophage-like cells. Macrophages were exposed (3 h) to extracts obtained from flours, and mitochondrial-associated oxygen consumption rates and inflammatory, metabolic, and proteome adaptations were quantified. Mass spectrometry 'm/z' signals of the extracts obtained from T. durum and A. sativa revealed molecular weights of 18-35 kDa and 16-22 kDa, respectively, for the compounds present at highest concentrations. Extracts from T. durum exhibited lower susceptibility to degradation by gastrointestinal enzymes than those from A. sativa: 9.5% vs 20.2%. Despite their different botanical origin, both extracts increased TLR4 expression. Metabolic protein levels were indicative of a decreased glycolytic to lactate flux in cell cultures upon stimulation with A. sativa extracts, which improved mitochondrial respiration in relation to those from T. durum. Principal components analysis confirmed relative similarities between immune-metabolic events triggered by immunonutritional ingredients in T. durum and A. sativa. Collectively, immunonutritional effects help to interpret the differences between both crops, worsening or improving, macrophage immune reactivity (tolerogenicity), and better control of inflammatory processes.

Acceptance of oat-based beverages tailored for patients with cancer.

Oat-based beverages are a nutritious product with the potential to support increased nutrient intake of patients with cancer. The aim of this research was to evaluate the sensory acceptance of oat-based beverages and perceptions of oats among patients with cancer as future vehicles for nutrient delivery. In study 1, three flavors of oat-beverages were well accepted without significant difference in liking among flavors or serving temperature, or between patients with cancer and healthy participants. Patients with cancer more frequently rated the beverages as too sweet compared to healthy participants; flavor intensity was just about right for all participants. In the second study, one of two formulations fortified with protein and fish oil was not different in liking compared to the unfortified chocolate product. Patients associated oat food products with specific oat-based food products and oat health benefits in a free-word association task in the third study. Together, sensory acceptance and the perceived health benefits of oats indicate the potential for oats to be incorporated in fortified and unfortified products tailored for patients with cancer. PRACTICAL APPLICATION: The three studies presented here to assess the sensory acceptance of oat-based beverages and perceptions of oats among patients with cancer demonstrate that oats can be incorporated in fortified and unfortified products tailored for patients with cancer. Inadequate nutrition is highly prevalent among oncology patients and there is a lack of available products targeted to improve their nutritional intake. These findings can support product developers and sensory scientists in the development and evaluation of food products acceptable to this population.

QM calculations predict the energetics and infrared spectra of transient glutamine isomers in LOV photoreceptors.

Photosensory receptors containing the flavin-binding light-oxygen-voltage (LOV) domain are modular proteins that fulfil a variety of biological functions ranging from gene expression to phototropism. The LOV photocycle is initiated by blue-light and involves a cascade of intermediate species, including an electronically excited triplet state, that leads to covalent bond formation between the flavin mononucleotide (FMN) chromophore and a nearby cysteine residue. Subsequent conformational changes in the polypeptide chain arise due to the remodelling of the hydrogen bond network in the cofactor binding pocket, whereby a conserved glutamine residue plays a key role in coupling FMN photochemistry with LOV photobiology. Although the dark-to-light transition of LOV photosensors has been previously addressed by spectroscopy and computational approaches, the mechanistic basis of the underlying reactions is still not well understood. Here we present a detailed computational study of three distinct LOV domains: EL222 from Erythrobacter litoralis, AsLOV2 from the second LOV domain of Avena sativa phototropin 1, and RsLOV from Rhodobacter sphaeroides LOV protein. Extended protein-chromophore models containing all known crucial residues involved in the initial steps (femtosecond-to-microsecond) of the photocycle were employed. Energies and rotational barriers were calculated for possible rotamers and tautomers of the critical glutamine side chain, which allowed us to postulate the most energetically favoured glutamine orientation for each LOV domain along the assumed reaction path. In turn, for each evolving species, infrared difference spectra were constructed and compared to experimental EL222 and AsLOV2 transient infrared spectra, the former from original work presented here and the latter from the literature. The good agreement between theory and experiment permitted the assignment of the majority of observed bands, notably the ∼1635 cm-1 transient of the adduct state to the carbonyl of the glutamine side chain after rotation. Moreover, both the energetic and spectroscopic approaches converge in suggesting a facile glutamine flip at the adduct intermediate for EL222 and more so for AsLOV2, while for RsLOV the glutamine keeps its initial configuration. Additionally, the computed infrared shifts of the glutamine and interacting residues could guide experimental research addressing early events of signal transduction in LOV proteins.