Effects Of Individual Amino Acids Research Articles

Genome-scale metabolic modeling of Thraustochytrium sp. RT2316-16: Effects of nutrients on metabolism.

Marine thraustochytrids produce metabolically important lipids such as the long-chain omega-3 polyunsaturated fatty acids, carotenoids, and sterols. The growth and lipid production in thraustochytrids depends on the composition of the culture medium that often contains yeast extract as a source of amino acids. This work discusses the effects of individual amino acids provided in the culture medium as the only source of nitrogen, on the production of biomass and lipids by the thraustochytrid Thraustochytrium sp. RT2316-16. A reconstructed metabolic network based on the annotated genome of RT2316-16 in combination with flux balance analysis was used to explain the observed growth and consumption of the nutrients. The culture kinetic parameters estimated from the experimental data were used to constrain the flux via the nutrient consumption rates and the specific growth rate of the triacylglycerol-free biomass in the genome-scale metabolic model (GEM) to predict the specific rate of ATP production for cell maintenance. A relationship was identified between the specific rate of ATP production for maintenance and the specific rate of glucose consumption. The GEM and the derived relationship for the production of ATP for maintenance were used in linear optimization problems, to successfully predict the specific growth rate of RT2316-16 in different experimental conditions.

Discovery of the biostimulant effect of asparagine and glutamine on plant growth in Arabidopsis thaliana.

Protein hydrolysates have gained interest as plant biostimulants due to their positive effects on plant performances. They are mainly composed of amino acids, but there is no evidence of the role of individual of amino acids as biostimulants. In this study we carried out in vitro experiments to monitor the development of Arabidopsis seedlings on amino acid containing media in order to analyze the biostimulant properties of the twenty individual proteinogenic amino acids. We demonstrated that proteinogenic amino acids are not good nitrogen sources as compared to nitrate for plant growth. Biostimulant analyses were based on leaf area measurements as a proxy of plant growth. We developed the Amino Acid Use Efficiency index to quantify the biostimulating effect of individual amino acids in the presence of nitrate. This index allowed us to classify amino acids into three groups, characterized by their inhibiting, neutral, and beneficial effects regarding leaf area. Glutamine and asparagine demonstrated the most significant effects in promoting leaf area in the presence of nitrate supply. The stimulating effect was confirmed by using the L and D enantiomeric forms. Both L-glutamine and L-asparagine stimulated leaf area at low concentrations, emphasizing their biostimulating properties. Our plant growth design and AAUE index pave the way for the identification of other bioactive molecules in protein hydrolysates and for the comparison of biostimulant performances.

Effects of Individual Amino Acids on the Blood Circulation of Biosynthetic Protein Nanocages: Toward Guidance on Surface Engineering (Adv. Healthcare Mater. 26/2023)

Effects of Individual Amino Acids on the Blood Circulation of Biosynthetic Protein Nanocages: Toward Guidance on Surface Engineering (Adv. Healthcare Mater. 26/2023)

Effects of Individual Amino Acids on the Blood Circulation of Biosynthetic Protein Nanocages: Toward Guidance on Surface Engineering.

Protein nanocages (PNCs) hold great promise for developing multifunctional nanomedicines. Long blood circulation is a key requirement of PNCs for most in vivo application scenarios. In addition to the classical PEGylation strategy, short peptides with a specific sequence screened via phage display are also very effective in prolonging the blood half-life (t1/2 ) of PNCs. However, there is a lack of knowledge on how individual amino acids affect the circulation of PNCs. Here the effects of the 20 proteinogenic amino acids in the form of an X3 or X5 tag (X represents an amino acid) are explored on the pharmacokinetics of PNCs, which lead to the formation of a heatmap illustrating the extent of t1/2 prolongation by each proteinogenic amino acid. Significantly, oligo-lysine and oligo-arginine can effectively prolong the t1/2 of strongly negatively charged PNCs through charge neutralization, while oligo-cysteine can also do so, but via a different mechanism, mediating the covalent binding of PNCs with plasma albumin as a stealth material. These findings are extendible and offer guidance for surface-engineering biosynthetic PNCs and other nanoparticles.

Enhanced Carbon Dioxide Capture Using a Mixed Amino Acid Salt Solution

This study investigated the carbon dioxide (CO2) absorption and desorption performance of a mixed amino acid solution (containing glycine (G), alanine (A), proline (P), and lysine (L), GAPL). These four amino acids were intentionally selected to reflect the chemical and structural variations (pKa and steric hindrance of amino groups) of amino acids. The single cycle CO2 capture experiment showed that the GAPL salt solution had 19% higher CO2 absorption (0.91 mol CO2/mol amino acids) compared to the absorption calculated by adding the proportional capacities of G, A, P, and L (0.77 mol CO2/mol amino acids). 13C NMR data delineated the effects of individual amino acids on carbamate and bicarbonate/carbonate formation and elucidated the distribution of captured CO2 in the GAPL salt solution. The recirculation experiment concluded that the GAPL salt solution had much better CO2 capture performance than the conventional monoethanolamine process. Less than 10% of the absorption and cyclic capacity of the GAPL salt solution was lost after ten cycles of CO2 capture. This study demonstrated an approach that blended amino acid solutions can be tailored and designed as new, efficient reagents to massively capture CO2 in a technically feasible, economically viable, and environmentally friendly manner.

Effect of L-Tryptophan and L-Glutamic Acid on Carrot Yield and Its Quality

Positively affecting crop quality and yields, amino acids used as plant stimulants play a special role in ensuring global food security. L-tryptophan (L-Try) and L-glutamic acid (L-Glu) are important biostimulants that increase the yield of field crops and vegetables. Carrot is one of the most important vegetables due to its production volume in the world (sixth most consumed vegetable) and its nutritional value. The response of different plant species to amino acid application varies. The literature mainly deals with the effects of ready-made products containing a mixture of several amino acids, with no exhaustive studies on the effects of individual amino acids on carrot quality and yield. This paper is based on a two-year field experiment (2019–2020), in which the effect of two amino acids, L-Trp (7.5 g·ha−1) and L-Glu (60.0 g·ha−1), on carrot (Daucus carota L.) was investigated. They were applied to the leaves (FA) or both to the soil and to the leaves (S + FA), separately, (L-Trp or L-Glu) or as a mixture (L-Trp + L-Glu). The control plot was treated with mineral fertilizers only. The research was conducted as a field experiment in a split-block design. The yield of carrot storage roots and their content of dry matter, protein, sugars, total soluble solids (TSS), and ascorbic acid were determined. The amino acids positively affected the yield of carrots compared to the control, but only the synergistic action of L-tryptophan and L-glutamic acid increased it significantly. On average, for both amino acids the S + FA application increased the protein content and the marketable yield of storage roots significantly more than in response to FA treatment. A significant increase in marketable yield compared to the control was found after the combined soil and foliar application (S + FA) of all amino acid combinations, but the L-Trp + L-Glu mixture worked best. The storage roots of carrots grown on the plot with L-Trp + L-Glu contained significantly more protein and TSS than those on the control plot. The content of TSS was also positively affected by L-Trp used on its own, while L-Glu increased the content of ascorbic acid. Amino acids applied to the leaves (FA) increased the content of total sugars in the carrot roots more than when applied both to the soil and to the leaves (S + FA). Of all treatment combinations, the synergistic action of L-Trp and L-Glu made it possible to obtain the highest yields of carrot storage roots, containing the most protein and total soluble solids.

Associations of serum amino acids with insulin resistance among people with and without overweight or obesity: A prospective study in Japan

Limited evidence exists regarding the prospective associations between amino acids and insulin resistance. In addition, amino acids have been suggested to promote insulin resistance with the requirement of obesity in animal studies, but the interaction between amino acids and obesity on the development of insulin resistance has not been examined in epidemiological studies. We aimed to investigate the differences in the prospective associations of serum amino acids with insulin resistance among adults with and without overweight or obesity. Fasting serum concentrations of 25 amino acids were quantified in 1131 non-diabetic Japanese workers aged 22-71 years at baseline. The homeostasis model assessment of insulin resistance (HOMA-IR) was estimated at baseline and the 3-year follow-up. Generalized linear models were used to assess the associations between amino acids at baseline and HOMA-IR at follow-up with adjustment for potential confounding factors. A Bonferroni-corrected threshold of p=0.001 was considered significant for multiple tests. The associations for the following amino acids with HOMA-IR at the 3-year follow-up significantly varied by obesity status: isoleucine, valine, tyrosine, alanine, and methionine (all p for interaction <0.05). Higher concentrations of serum isoleucine, valine, tyrosine, and alanine (per 1SD) were significantly associated with higher HOMA-IR levels in overweight/obese participants (multivariable-adjusted β coefficients ranging from 0.09 to 0.12; all p<0.001), but no association was observed in the underweight/normal-weight participants. The associations for serum methionine were direct among overweight/obese participants, but inverse among underweight/normal-weight participants (all p<0.001). This study demonstrated the prospective associations of different individual serum amino acids with insulin resistance, with most pronounced associations being for overweight/obese adults. Our findings support the possibility of heterogeneous effects of individual amino acids, as well as their interplay with obesity in the progression of insulin resistance.

Effects of Individual Amino Acids on PPARα Transactivation, mTORC1 Activation, ApoA-I Transcription and pro-ApoA-I Secretion.

A higher concentration of apolipoprotein A-I (ApoA-I) is associated with increased high density lipoprotein functionality and reverse cholesterol transport (RCT). A promising strategy to prevent cardiovascular diseases is therefore to improve RCT by increasing de novo ApoA-I production. Since experimental animal models have suggested effects of amino acids on hepatic lipoprotein metabolism, we here examined the effects of different amino acids on hepatic ApoA-I production. Human hepatocytes (HepG2) were exposed to six individual amino acids for 48 h. ApoA-I transcription and secreted pro-ApoA-I protein concentrations were analyzed using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assays (ELISA), respectively. Additionally, CPT1 and KEAP1 mRNA expression, peroxisome proliferator-activated receptor alpha (PPARα) transactivation, and mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation were determined. Leucine, glutamic acid, and tryptophan increased ApoA-I and CPT1 mRNA expression. Tryptophan also strongly increased PPARα transactivation. Glutamine, proline, and histidine increased pro-ApoA-I protein concentrations but mTORC1 phosphorylation remained unchanged regardless of the amino acid provided. In conclusion, individual amino acids have different effects on ApoA-I mRNA expression and pro-ApoA-I production which can partially be explained by specific effects on PPARα transactivation, while mTORC1 phosphorylation remained unaffected.

Amino acids, ammonia, and hepatic encephalopathy

Hepatic encephalopathy (HE) is a decline in brain function arising due to liver insufficiency. The liver's diminished capacity to clear ammonia, and the subsequent accumulation of it, is highly implicated in pathogenesis of HE. Ammonia is endogenously generated from the catabolism of amino acids derived from dietary protein intake. Therefore, a conflict arises in cirrhosis where dietary protein intake may increase ammonia and precipitate HE, and at the same time, cirrhotic patients require high daily protein intake due to altered nutrient metabolism. A nutritional solution is needed to deliver sufficient doses of protein to patients without increasing the risk of HE. In order to address this issue, this review will discuss the catabolism of individual amino acids with a special focus on ammonia-generating steps and highlight a subset of amino acids that have the potential to generate multiple equivalents of ammonia. Following, studies investigating the effects of individual amino acids in cirrhosis on blood ammonia levels as well as development of HE will be reviewed.

Is the amino acid pattern in medical nutrition therapy crucial for successfully attenuating muscle mass loss in adult ICU patients? Secondary analysis of a RCT.

We hypothesized that in long-term immobilized intensive care unit (ICU) patients, both the quantity and quality of protein nutrition are vital in supporting muscle mass maintenance. Hence, the aim of this secondary analysis of our recently performed RCT was to calculate the intake of individual amino acids and to evaluate the potential associations of amino acid patterns with muscle mass loss during the ICU stay. Clinical and nutritional data were collected from a recent RCT conducted in long-term immobilized, critically ill patients receiving medical nutrition therapy with either 1.8g (interventional group) or 1.2g (standard group) of protein/amino acids per kg body weight per day over 4 weeks. Intake of the individual amino acids as well as the sum scores of the indispensable, conditionally indispensable, and dispensable amino acids were calculated for all patients, both group specific (n=21 in each group) and in total (n=42), based on the detailed nutrition protocols; inter-group differences were analyzed by t-tests. Linear regression models were used to test the effects of individual amino acids and the sum scores on the extent of skeletal muscle loss by measuring the quadriceps muscle layer thickness during the study period. The significance level was adjusted for multiple testing according to the Bonferroni procedure (α=0.002). In both groups, the proportion of indispensable amino acids was approximately 41% of the total exogenous protein supply, with the proportion of enteral administration slightly over 50%. The intake of conditionally indispensable amino acids (glutamine, tyrosine, cysteine, histidine, and arginine) accounted for 17% and 18% of the total amino acids in the interventional and standard groups, respectively; glutamine (5% of total amino acids) was exclusively administered enterally. The intake of dispensable amino acid varied widely, with glutamic acid, proline, and asparagine/aspartic acid representing the highest proportions (10%, 8%, and 8% of total amino acids, respectively). For all amino acids, no statistically significant association was observed between the quantitative intake and the skeletal muscle changes after terminating the intervention phase. This secondary analysis of the RCT conducted in routine clinical practice did not support our working hypothesis that the amino acid patterns of medical nutrition therapy have a statistically significant impact on the skeletal muscle loss in long-term immobilized ICU patients. Due to the limited variety of enteral/parenteral products used in this single-center study, the calculated amino acid patterns showed only small differences. Larger multi-center trials with adequate power are needed to evaluate the potential effects of the individual amino acids or defined amino acid patterns on the muscle protein metabolism in further detail. German Clinical Trials Register (http://www.drks.de); DRKS-ID: DRKS00013594.

Genetic deletion of mitochondrial PEP carboxykinase (PCK2) in pancreatic α cells increases amino acid-stimulated Ca2+ influx and boosts the excitability of neighboring β-cells

Amino acids potently stimulate glucagon secretion, but their mechanisms of action remain largely unknown. To assess the effects of individual amino acids on α-cell Ca2+, we used GcgCreERT:GCaMP6s Ca2+ reporter mice in combination with epifluorescence and light-sheet imaging to monitor the behavior of single α-cells within the intact islet. We focused on alanine, arginine, glutamine, and leucine, which have the potential to affect Ca2+ and glucagon release via their transport or metabolism. At low glucose, when β-cells are inactive, alanine and arginine provoked a sustained increase in Ca2+.

Paracellular calcium flux across Caco-2 cell monolayers: Effects of individual amino acids

High-protein diets are generally considered beneficial for calcium (Ca) economy and bone health. Improved intestinal Ca absorption efficiency may be one mechanism by which higher-protein diets affect Ca homeostasis and bone health. The signaling pathways and individual amino acids (AA) responsible for this effect have not been fully elucidated and may involve the transcellular pathway, paracellular pathway or a combination. The primary aim of this study was to investigate whether a mixture of AA and/or functionally distinct individual AA directly affect paracellular Ca absorption across an intestinal epithelial cell model (Caco-2 Bbe). Using Ussing chambers, we examined the effect of six treatments — vehicle (Veh), 80 mM raffinose (Raf; positive control), 2× mixed AA(2×AA, twice the concentration in standard growth media), the branched-chain amino acid leucine (2–10 mM Leu), the aromatic amino acid phenylalanine (2–10 mM Phe) and the dibasic amino acid lysine (2–10 mM Lys) — on Ca flux. Leu (5 mM) increased Ca flux by 38% (+122 nmol Ca/cm2/h, P<.001) as compared to Veh, while 10 mM Phe reduced Ca flux. No other differences were observed. Leu increased Ca flux through cellular redistribution of the Ca permissive channel Cldn-2 to the tight junction membrane (P<.05). Inhibition of mTORC1 signaling did not abrogate the effect of Leu on Cldn-2 localization, indicating a non-mTORC1-dependent signaling pathway is involved. These data indicate that Leu may improve Ca absorption in a cell model, potentially contributing to the observed benefits of higher-protein diets on bone health in humans.

Metabolic Regulation of Pre- and Postnatal Growth.

Growth characteristics during periods of early developmental plasticity are linked with later health outcomes and with disease risks. Infant growth is modulated by genetic and exogenous factors including nutrition. We try to explore their underlying mechanisms using targeted metabolomic profiling of small molecules in biological samples using high-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) to quantify hundreds of molecules in small biosamples, e.g., 50 µL plasma. In the large German LISA birth cohort study, cord blood lysophosphatidylcholines and fatty acids were closely associated with infant birth weight, with a nonsignificant trend towards an association with infant weight gain and later BMI. Studies in infants randomized to different protein intakes in the European CHOP Study show conventional high protein intakes to markedly increase plasma-indispensable amino acids (AA), particularly branched-chain AA (BCAA), while exceeding the infant's capacity of BCAA breakdown, and an increase in the dispensable AA tyrosine previously associated with insulin resistance. In a path model analysis of the relationship of infant plasma AA, growth factors, and infant growth, AA were generally found to induce a stronger response of insulin than IGF-I although effects of individual AA were very different. We conclude that targeted improvement in nutrient supply in pregnancy and infancy may offer large opportunities for promoting desirable child growth patterns and long-term health.

Parsing the life-shortening effects of dietary protein: effects of individual amino acids.

High-protein diets shorten lifespan in many organisms. Is it because protein digestion is energetically costly or because the final products (the amino acids) are harmful? To answer this question while circumventing the life-history trade-off between reproduction and longevity, we fed sterile ant workers on diets based on whole proteins or free amino acids. We found that (i) free amino acids shortened lifespan even more than proteins; (ii) the higher the amino acid-to-carbohydrate ratio, the shorter ants lived and the lower their lipid reserves; (iii) for the same amino acid-to-carbohydrate ratio, ants eating free amino acids had more lipid reserves than those eating whole proteins; and (iv) on whole protein diets, ants seem to regulate food intake by prioritizing sugar, while on free amino acid diets, they seem to prioritize amino acids. To test the effect of the amino acid profile, we tested diets containing proportions of each amino acid that matched the ant's exome; surprisingly, longevity was unaffected by this change. We further tested diets with all amino acids under-represented except one, finding that methionine, serine, threonine and phenylalanine are especially harmful. All together, our results show certain amino acids are key elements behind the high-protein diet reduction in lifespan.

Can feeding the broiler breeder improve chick quality and offspring performance?

The impact of nutrition on the performance of broiler breeders in terms of bodyweight profile, egg production, egg size and shell quality, mortality, fertility and hatchability has been well documented. However, studies on the direct effects of breeder nutrition on subsequent chick quality and offspring performance are limited. The present paper reviews the nutritional factors in broiler breeders that may improve chick quality and progeny performance. Recent research has suggested that the feeding of low crude protein and medium to high energy breeder diets in both rearing and laying period will not only have a positive impact on egg production, egg size, breeder fertility, hatchability and embryonic livability, but also on offspring performance. Improvements include better chick quality, higher chick weight, lower mortality, increased immune responses, enhanced litter quality and broiler growth. Breast-meat yield in the progeny can be improved as the energy to protein ratio increases from the rearing phase to the laying phase, indicating that nutrition of pullets can also affect growth and yields. The effects of maternal diet on offspring performance may depend on the sex of the progeny, with male broilers responding more than female broilers to breeders’ dietary protein and energy concentrations. However, little work has been conducted on the effects of individual amino acids in breeder diets on the subsequent generation. There seems to be some benefits with the use of long-chain poly-unsaturated fats in breeder diets on carcass quality of offspring, but these effects appear inconsistent at this stage. There is substantial evidence that confirms the direct effects of vitamin D and E, and trace minerals, especially in organic form, such as selenium, zinc and manganese, on chick quality and progeny performance. In fact, the impact of breeder nutrition on progeny performance in the field is more likely to be greater under conditions of poor breeder-flock uniformity, low vitamin and trace mineral contents or certain types of stress in the broiler house.

A comparative genomics study on the effect of individual amino acids on ribosome stalling.

BackgroundDuring protein synthesis, the nascent peptide chain emerges from the ribosome through the ribosomal exit tunnel. Biochemical interactions between the nascent peptide and the tunnel may stall the ribosome movement and thus affect the expression level of the protein being synthesized. Earlier studies focused on one model organism (S. cerevisiae), have suggested that certain amino acid sequences may be responsible for ribosome stalling; however, the stalling effect at the individual amino acid level across many organisms has not yet been quantified.ResultsBy analyzing multiple ribosome profiling datasets from different organisms (including prokaryotes and eukaryotes), we report for the first time the organism-specific amino acids that significantly lead to ribosome stalling. We show that the identity of the stalling amino acids vary across the tree of life. In agreement with previous studies, we observed a remarkable stalling signal of proline and arginine in S. cerevisiae. In addition, our analysis supports the conjecture that the stalling effect of positively charged amino acids is not universal and that in certain conditions, negative charge may also induce ribosome stalling. Finally, we show that the beginning part of the tunnel tends to undergo more interactions with the translated amino acids than other positions along the tunnel.ConclusionsThe reported results support the conjecture that the ribosomal exit tunnel interacts with various amino acids and that the nature of these interactions varies among different organisms. Our findings should contribute towards better understanding of transcript and proteomic evolution and translation elongation regulation.

Diversity of amino acid signaling pathways on autophagy regulation: A novel pathway for arginine

Autophagy is the intracellular bulk degradation process to eliminate damaged cellular machinery and to recycle building blocks, and is crucial for cell survival and cell death. Amino acids modulate autophagy in response to nutrient starvation and oxidative stress. We investigated the relevance of reactive oxygen species (ROS) production on the regulation of autophagy using amino acids, both as a mixture and individually, in rat hepatoma H4-II-E cells. Nutrient starvation elevated ROS production and stimulated autophagy. Treatment with complete (CAA), regulatory (RegAA) and non-regulatory (NonRegAA) amino acid mixtures showed significant suppression of ROS production, whereas only CAA and RegAA exhibited significant suppression of autophagy, suggesting a dissociation of the two responses. The effects of individual amino acids were examined. Leucine from RegAA decreased ROS production and suppressed autophagy. However, methionine and proline from RegAA and arginine, cystine and glutamic acid from NonRegAA suppressed autophagy with an opposite increase in ROS production. Other amino acids from the NonRegAA group showed stimulating effects on ROS production without an autophagic response. Arginine’s effect on autophagy suppression was not blocked by rapamycin, indicating an mTOR-independent pathway. Inhibitor studies on arginine-regulated autophagy may indicate the involvement of NO pathway, which is independent from ROS and mTOR pathways.

Building a Model of the Blue Cone Pigment Based on the Wild Type Rhodopsin Structure with QM/MM Methods

Understanding the mechanism of color tuning of the retinal chromophore by its host protein became one of the key issues in the research on rhodopsins. While early mutation studies addressed its genetic origin, recent studies advanced to investigate its structural origin, based on X-ray crystallographic structures. For the human cone pigments, no crystal structures have been produced, and homology models were employed to elucidate the origin of its blue-shifted absorption. In this theoretical study, we take a different route to establish a structural model for human blue. Starting from the well-resolved structure of bovine rhodopsin, we derive multiple mutant models by stepwise mutation and equilibration using molecular dynamics simulations in a hybrid quantum mechanics/molecular mechanics framework. Our 30fold mutant reproduces the experimental UV-vis absorption shift of 0.45 eV and provides new insights about both structural and genetic factors that affect the excitation energy. Electrostatic effects of individual amino acids and collaborative structural effects are analyzed using semiempirical (OM2/MRCI) and ab initio (SORCI) multireference approaches.

Isoleucine and Leucine Independently Regulate mTOR Signaling and Protein Synthesis in MAC-T Cells and Bovine Mammary Tissue Slices ,

Understanding the regulatory effects of individual amino acids (AA) on milk protein synthesis rates is important for improving protein and AA requirement models for lactation. The objective of this study was to examine the effects of individual essential AA (EAA) on cellular signaling and fractional protein synthesis rates (FSR) in bovine mammary cells. Omission of ʟ-arginine, ʟ-isoleucine, ʟ-leucine, or all EAA reduced (P< 0.05) mammalian target of rapamycin (mTOR; Ser2448) and ribosomal protein S6 (rpS6; Ser235/236) phosphorylation in MAC-T cells. Phosphorylation of mTOR and rpS6 kinase 1 (S6K1; Thr389) decreased (P< 0.05) in the absence of ʟ-isoleucine, ʟ-leucine, or all EAA in lactogenic mammary tissue slices. Omission of L-tryptophan also reduced S6K1 phosphorylation (P= 0.01). Supplementation of ʟ-leucine to media depleted of EAA increased mTOR and rpS6 and decreased eukaryotic elongation factor 2 (Thr56) phosphorylation (P< 0.05) in MAC-T cells. Supplementation of ʟ-isoleucine increased mTOR, S6K1, and rpS6 phosphorylation (P< 0.05). No single EAA considerably affected eukaryotic initiation factor 2-α (eIF2α; Ser51) phosphorylation, but phosphorylation was reduced in response to provision of all EAA (P< 0.04). FSR declined when ʟ-isoleucine (P= 0.01), ʟ-leucine (P= 0.01), ʟ-methionine (P= 0.02), or ʟ-threonine (P= 0.07) was depleted in media and was positively correlated (R= 0.64,P< 0.01) with phosphorylation of mTOR and negatively correlated (R= -0.42,P= 0.01) with phosphorylation of eIF2α. Such regulation of protein synthesis will result in variable efficiency of transfer of absorbed EAA to milk protein and is incompatible with the assumption that a single nutrient limits protein synthesis that is encoded in current diet formulation strategies.

The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.