scholarly journals Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR

2012 ◽  
Vol 449 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Jordan Gallinetti ◽  
Eylul Harputlugil ◽  
James R. Mitchell

DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.

2006 ◽  
Vol 188 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Swaroopa Atluri ◽  
Katerina Ragkousi ◽  
Donna E. Cortezzo ◽  
Peter Setlow

ABSTRACT The GerA nutrient receptor alone triggers germination of Bacillus subtilis spores with l-alanine or l-valine, and these germinations were stimulated by glucose and K+ plus the GerK nutrient receptor. The GerB nutrient receptor alone did not trigger spore germination with any nutrients but required glucose, fructose, and K+ (GFK) (termed cogerminants) plus GerK for triggering of germination with a number of l-amino acids. GerB and GerA also triggered spore germination cooperatively with l-asparagine, fructose, and K+ and either l-alanine or l-valine. Two GerB variants (termed GerB*s) that were previously isolated by their ability to trigger spore germination in response to d-alanine do not respond to d-alanine but respond to the same l-amino acids that stimulate germination via GerB plus GerK and GFK. GerB*s alone triggered spore germination with these l-amino acids, although GerK plus GFK stimulated the rates of these germinations. In contrast to l-alanine germination via GerA, spore germination via l-alanine and GerB or GerB* was not inhibited by d-alanine. These data support the following conclusions. (i) Interaction with GerK, glucose, and K+ somehow stimulates spore germination via GerA. (ii) GerB can bind and respond to l-amino acids, although normally either the binding site is inaccessible or its occupation is not sufficient to trigger spore germination. (iii) Interaction of GerB with GerK and GFK allows GerB to bind or respond to amino acids. (iv) In addition to spore germination due to the interaction between GerA and GerK, and GerB and GerK, GerB can interact with GerA to trigger spore germination in response to appropriate nutrients. (v) The amino acid sequence changes in GerB*s reduce these receptor variants' requirement for GerK and cogerminants in their response to l-amino acids. (vi) GerK binds glucose, GerB interacts with fructose in addition to l-amino acids, and GerA interacts only with l-valine, l-alanine, and its analogs. (vii) The amino acid binding sites in GerA and GerB are different, even though both respond to l-alanine. These new conclusions are integrated into models for the signal transduction pathways that initiate spore germination.


Author(s):  
Florian Javelle ◽  
Descartes Li ◽  
Philipp Zimmer ◽  
Sheri L. Johnson

Abstract. Emotion-related impulsivity, defined as the tendency to say or do things that one later regret during periods of heightened emotion, has been tied to a broad range of psychopathologies. Previous work has suggested that emotion-related impulsivity is tied to an impaired function of the serotonergic system. Central serotonin synthesis relies on the intake of the essential amino acid, tryptophan and its ability to pass through the blood brain barrier. Objective: The aim of this study was to determine the association between emotion-related impulsivity and tryptophan intake. Methods: Undergraduate participants (N = 25, 16 women, 9 men) completed a self-rated measure of impulsivity (Three Factor Impulsivity Index, TFI) and daily logs of their food intake and exercise. These data were coded using the software NutriNote to evaluate intakes of tryptophan, large neutral amino acids, vitamins B6/B12, and exercise. Results: Correlational analyses indicated that higher tryptophan intake was associated with significantly lower scores on two out of three subscales of the TFI, Pervasive Influence of Feelings scores r =  –.502, p < . 010, and (lack-of) Follow-Through scores, r =  –.407, p < . 050. Conclusion: Findings provide further evidence that emotion-related impulsivity is correlated to serotonergic indices, even when considering only food habits. It also suggests the need for more research on whether tryptophan supplements might be beneficial for impulsive persons suffering from a psychological disorder.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Andrew Matchado ◽  
Kathryn Dewey ◽  
Christine Stewart ◽  
Per Ashorn ◽  
Ulla Ashorn ◽  
...  

Abstract Objectives 1) to estimate the probability of inadequate amino acid intake among infants 9–10 months of age in rural Malawi 2) to evaluate whether dietary amino acid intake or protein quality are associated with length gain from 6 to 12 months of age Methods We assessed total amino acid intake from breast milk and complementary foods in 285 infants. Breast milk intake and complementary foods were estimated using dose-to-mother deuterium oxide dilution method and repeat 4-pass interactive 24-hour recall interviews, respectively. Amino acid composition values were taken from FAO human milk profile, Tanzania Food Composition table and International Minilist. Protein quality was estimated using Digestible Indispensable Amino Acid Score (DIAAS). Probability of intake below Estimated Average Requirement (EAR) for each amino acid was estimated using National Cancer Institute (NCI) method. We estimated protein quality of complementary food using median DIAAS. We assumed a DIAAS of ≥0.75 to represent a diet or food with good protein quality. Relationships between amino acid intake or protein quality with length gain were assessed using regression models. Length was measured at 6 and 12 months of age and length for age z-score (LAZ) velocity was calculated (ΔLAZ/months). Results The probability of inadequate amino acid intake from breast milk and complementary food that included a lipid-based nutrient supplement (LNS) was 3% for lysine, 0% for tryptophan, threonine, valine, histidine, isoleucine, leucine, sulfur containing amino acids (SAA), and aromatic amino acids (AAA). Without LNS, the probability was 7% for lysine and 0–2% for the other amino acids. The median (interquartile range) DIAAS for complementary food with and without LNS was 0.70 (0.28) and 0.64 (0.32), respectively. Dietary amino acid intake and protein quality were not significantly associated with length gain velocity from 6 to 12 months even after adjusting for confounding factors. Conclusions The prevalence of inadequate amino acid intake in 9–10 months old infants in rural Malawi is very low. However, in conditions of frequent clinical or sub-clinical infections this situation may be different. Linear growth at 6–12 months does not appear to be limited by dietary amino acid intake or protein quality in this setting. Funding Sources The Bill & Melinda Gates Foundation.


Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 675 ◽  
Author(s):  
Bo-Hyun Choi ◽  
Jonathan L. Coloff

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.


2021 ◽  
pp. 1-8
Author(s):  
Adeyeye EI ◽  
◽  
Idowu OT ◽  

This article reports the amino acid composition of the Nigerian local cheese called ‘wara’. ‘Wara’ is made by boiling cow milk with some added coagulant to cuddle the milk protein resulting in coagulated milk protein and whey. ‘Wara’ used to be an excellent source of nutrients such as proteins, fats, minerals and vitamins. Samples were purchased in Ado-Ekiti, Nigeria. Amino acid values were high (g/100g crude protein) in Leu, Asp, Glu, Pro, Phe, Arg with total value of 97.7. The quality parameters of the amino acids were: TEAA (42.6g/100g and 43.6%) whereas TNEAA (55.1g/100g and 56.4%); TArAA (12.8g/100g and 13.1%); TBAA (14.2g/100g and 14.5%); TSAA (3.10g/100g and 3.17%); %Cys in TSAA (51.4); Leu/Ile ratio (1.74); P-PER1 (2.65); P-PER2 (2.48); P-PER3 (2.41); EAAI1 (soybean standard) (1.29) and EAAI2 (egg standard) (99.9); BV (97.2) and Lys/Trp ratio (3.62). The statistical analysis of TEAA/TNEAA at r=0.01 was not significantly different. On the amino acid scores, Met was limiting (0.459) at egg comparison, Lys was limiting at both FAO/WHO [24] and preschool EAA requirements with respective values of 0.966 and 0.97. Estimates of essential amino acid requirements at ages 10-12 years (mg/kg/day) showed the ‘wara’ sample to be better than the standard by 3.72-330% with Lys (3.72%) being least better and Trp (330%) being most. The results showed that ‘wara’ is protein-condensed which can be eaten as raw cheese, flavoured snack, sandwich filling or fried cake.


Food systems ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 4-11
Author(s):  
S. V. Zverev ◽  
V. I. Karpov ◽  
M. A. Nikitina

The paper emphasizes the importance of not only the quantitative but also qualitative composition of protein in nutrition. The authors propose protein classification into three main groups according to the concept of reference (ideal) protein. A mathematical model is examined to solve the task of rational mixture production upon the given profile of reference protein. Two variants of the criterion for formation of optimal composition are described. One of them presents the classical sum of squares of the residual for essential amino acid scores and 1. The second also presents the sum of squares of the residual for essential amino acid scores and 1 but with regard to only those amino acids, which scores are less than 1. The minima of these criteria at the set of variants for the content of ingredients are taken as targeted functions. The algorithm and the program of calculation were realized in the program environment Builder C++ 6.0. The macro flowchart of the algorithm is presented and detailed description of each block is given. The program interface before and after the start of the calculation module is shown. The main windows and interpretation of the presented data are described. An example of realization of the proposed mathematical apparatus when calculating a food model composition is given. Plant components (white kidney beans, flax, peanut, grit “Poltavskaya», dry red carrot) were used as an object of the research. Most plant proteins were incomplete. It is possible to regulate the chemical composition including correction of a protein profile by combination of plant raw materials. Analysis of alternative variants demonstrated that minimum essential amino acid score in the first composition was 0.79 (by the first criterion), in the second 1.0 (by the second criterion); the reference protein proportion in the mixture was 10.8 and 13.5, respectively, according to the first and second criterion. The comparative results by other quality indicators for protein in the mixture are also presented: the coefficient of amino acid score difference (CAASD), biological value (BV), coefficient of utility, essential amino acids index (IEAA).


Aging ◽  
2014 ◽  
Vol 6 (5) ◽  
pp. 390-398 ◽  
Author(s):  
Sahar Emran ◽  
Mingyao Yang ◽  
Xiaoli He ◽  
Jelle Zandveld ◽  
Matthew D. W. Piper

2002 ◽  
Vol 184 (5) ◽  
pp. 1444-1448 ◽  
Author(s):  
Jayna L. Ditty ◽  
Caroline S. Harwood

ABSTRACT Charged amino acids in the predicted transmembrane portion of PcaK, a permease from Pseudomonas putida that transports 4-hydroxybenzoate (4-HBA), were required for 4-HBA transport, and they were also required for P. putida to have a chemotactic response to 4-HBA. An essential amino acid motif (DGXD) containing aspartate residues is located in the first transmembrane segment of PcaK and is conserved in the aromatic acid/H+ symporter family of the major facilitator superfamily of transporters.


Sign in / Sign up

Export Citation Format

Share Document