scholarly journals Ammonium-Dependent Shortening of CLS in Yeast Cells Starved for Essential Amino Acids Is Determined by the Specific Amino Acid Deprived, through Different Signaling Pathways

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Júlia Santos ◽  
Cecília Leão ◽  
Maria João Sousa

Ammonium (NH4+) leads to chronological life span (CLS) shortening inSaccharomyces cerevisiaeBY4742 cells, particularly evident in cells starved for auxotrophy-complementing amino acids (leucine, lysine, and histidine) simultaneously. Here, we report that the effect ofNH4+on aging yeast depends on the specific amino acid they are deprived of. Compared with no amino acid starvation, starvation for leucine alone or in combination with histidine resulted in the most pronouncedNH4+-induced CLS shortening, whereas starvation for lysine, alone or in combination with histidine resulted in the least sensitivity toNH4+. We also show thatNH4+-induced CLS shortening is mainly mediated by Tor1p in cells starved for leucine or histidine but by Ras2p in cells starved for lysine, and in nonstarved cells. Sch9p protected cells from the effect ofNH4+under all conditions tested (starved or nonstarved cells), which was associated with Sch9p-dependent Hog1p phosphorylation. Our data show thatNH4+toxicity can be modulated through manipulation of the specific essential amino acid supplied to cells and of the conserved Ras2p, Tor1p, and Sch9p regulators, thus providing new clues to the development of environmental interventions for CLS extension and to the identification of new therapeutic targets for diseases associated with hyperammonemia.

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.


1990 ◽  
Vol 97 (3) ◽  
pp. 479-485
Author(s):  
J.R. Jara ◽  
J.H. Martinez-Liarte ◽  
F. Solano ◽  
R. Penafiel

The uptake of L-Tyr by B16/F10 malignant melanocytes in culture has been studied. These melanoma cells can either be depleted of amino acids by 1 h preincubation in Hanks' isotonic medium or preloaded with a specific amino acid by 1 h preincubation in the same solution containing 2 mM of the amino acid to be preloaded. By means of these pretreatments, it is shown that the rate of L-Tyr uptake is greatly dependent on the content of other amino acids inside the cells. The L-Tyr uptake is higher in cells preloaded with amino acids transported by the L and ASC systems than in cells depleted of amino acids or preloaded with amino acids transported by the A system. It is concluded that L-Tyr is mainly taken up by an exchange mechanism with other amino acids mediated by the L1 system, although the ASC system can also participate in the process. In agreement with that, the homo-exchange performed by cells preloaded with unlabelled L-Tyr is more efficient than any other hetero-exchange, although L-Dopa, the product of tyrosine hydroxylation in melanin synthesis, is almost as efficient as L-Tyr. Apart from aromatic amino acids, melanoma cells preloaded with L-Met and L-His also yield a high initial rate of L-Tyr uptake. The results herein suggest that melanoma cells do not have transport systems specific for L-Tyr, even if this amino acid is needed to carry out the differential pathway of this type of cells, melanosynthesis.


2015 ◽  
Vol 74 (4) ◽  
pp. 378-386 ◽  
Author(s):  
Mary Hickson

The aim of the present paper is to critically review the details of the published nutrition intervention trials, with and without exercise, targeting sarcopenia. Sarcopenia is the loss of muscle mass, strength and/or performance with age. Since amino acids and energy are required for muscle synthesis it is possible that nutritional intake influences sarcopenia. Nutritional studies are challenging to carry out because of the complexity of modulating dietary intake. It is very difficult to change one nutrient without influencing many others, which means that many of the published studies are problematic to interpret. The studies included evaluate whole protein, essential amino acids and β-hydroxyl β-methylbutyrate (HMB). Whole-protein supplementation failed to show a consistent effect on muscle mass, strength or function. This can be explained by the variations in study design, composition of the protein supplement and the failure to monitor voluntary food intake, adherence and baseline nutritional status. Essential amino-acid supplements showed an inconsistent effect but there are only two trials that have significant differences in methodology and the supplement used. The HMB studies are suggestive of a beneficial effect on older adults, but larger well-controlled studies are required that measure outcomes relevant to sarcopenia, ideally in sarcopenic populations. The issues of timing and distribution of protein intake, and increased splanchnic amino-acid sequestration are discussed, and recommendations for future trials are made.


1985 ◽  
Vol 54 (2) ◽  
pp. 499-508 ◽  
Author(s):  
J. Heger ◽  
Z. Frydrych

1. Nitrogen balance was studied in growing male SPF-rats fed on diets in which each essential amino acid was varied from zero to about 120% of optimum requirement. From the balance results, optimum and maintenance requirements were estimated as well as the efficiency of utilization of amino acids for growth and growth + maintenance.2. N balance increased with increasing dietary level of the deficient amino acid; the response gradually diminished as the content of the amino acid approached optimum. At zero level of intake, negative N balance was found for all amino acids except histidine. The highest loss of body N was found in the sulphur-amino-acid-free diet and the lowest one in the lysine-free diet.3. Maximal utilization of essential amino acids for growth was found at dietary levels corresponding to 30–60% of optimum requirement and ranged from about 0.65 to 0.85 except for S amino acids and histidine. The utilization of S amino acids was about 0.55 while that of histidine exceeded 1.0. The utilization of amino acids for growth-tmaintenance was maximal at the lowest levels of intake and gradually decreased as the dietary concentration of the limiting amino acid increased. At dietary levels near optimum the utilization was about 06–07, except for S amino acids where the utilization was less than 0.5.


2008 ◽  
Vol 276 (1658) ◽  
pp. 987-991 ◽  
Author(s):  
E Akman Gündüz ◽  
A.E Douglas

Animals generally require a dietary supply of various nutrients (vitamins, essential amino acids, etc.) because their biosynthetic capabilities are limited. The capacity of aphids to use plant phloem sap, with low essential amino acid content, has been attributed to their symbiotic bacteria, Buchnera aphidicola , which can synthesize these nutrients; but this has not been demonstrated empirically. We demonstrate here that phloem sap obtained from the severed stylets of pea aphids Acyrthosiphon pisum feeding on Vicia faba plants generally provided inadequate amounts of at least one essential amino acid to support aphid growth. Complementary analyses using aphids reared on chemically defined diets with each amino acid individually omitted revealed that the capacity of the symbiotic bacterium B. aphidicola to synthesize essential amino acids exceeded the dietary deficit of all phloem amino acids except methionine. It is proposed that this shortfall of methionine was met by aphid usage of the non-protein amino acid 5-methylmethionine in the phloem sap. This study provides the first quantitative demonstration that bacterial symbiosis can meet the nutritional demand of plant-reared aphids. It shows how symbiosis with micro-organisms has enabled this group of animals to escape from the constraint of requiring a balanced dietary supply of amino acids.


1998 ◽  
Vol 66 (1) ◽  
pp. 285-292 ◽  
Author(s):  
M. García-Gallego ◽  
H. Akharbach ◽  
M. de la Higuera

AbstractThis experiment was conducted to test two different protein sources as alternatives to the commonly used fish meal (FM) in the diet of the European eel (Anguilla anguilla). Six experimental diets were tested in three replicated lots of European eels. All diets contained the same protein and energy content (ca, 300 g crude protein per kg dry matter and 18·5 MJ/kg, respectively) but differed in the nature of the protein source: FM was the only protein source in the control diet and was fully or partially (0–5: 0–5) replaced by meat meal (MM) or sunflower meal (SFM) in four other diets; a sixth diet included SFM as the only protein source but was supplemented with several essential amino acids. Food intake, fish growth and several indices of diet and protein utilization were measured. MM clearly was the poorest protein source while SFM could replace, at least 0·5 of the FM with no significant reduction in performance. In addition, the European eel was able to utilize the supplement of essential amino acids. The full-SFM diet was improved significantly when supplemented and results were not statistically different from the control FM-based diet. Overall, a good correlation was found between the results of each diet and the respective essential amino acid index, calculated using as reference the essential amino acid requirements previously defined for another eel species, Anguilla japonica. This index could be used as a reliable measure for an a priori evaluation of alternative protein sources to be included in commercial foods for eels.


2021 ◽  
Vol 7 (2) ◽  
pp. 138-146
Author(s):  
Pranta Das ◽  
Md Salman ◽  
Md Aminur Islam ◽  
Sharmin Suraiya ◽  
Monjurul Haq

Dried shrimp has some special advantageous such as long shelf-life, high nutritional content, and ease of transportation considered as a healthy choice of food. The nutritional properties of three common and demandable dried shrimp species available in Jashore, Bangladesh were evaluated. The moisture content of dried Palaemon karnafuliensis, Metapenaeus Monoceros and Ferapenaeus indicus was determined 19.7±0.40%, 20.5±0.25% and 24.9±0.21%, respectively. The protein content was found 57.46±5.88%, 62.5±1.98%, and 55.5±1.85% in Palaemon karnafuliensis, Metapenaeus Monoceros, and Ferapenaeus indicus, respectively. The ash and fat content of Palaemon karnafuliensis, Metapenaeus Monoceros and Ferapenaeus indicus were observed 12.20±0.90% and 1.90±0.15%, 10.20±0.39% and 1.48±0.32%, 8.57±1.43%, and 1.08±0.21%, respectively. Total saturated fatty acids content was found 31.56%, 29.21%, 38.59 in Palaemon karnafuliensis, Metapenaeus monoceros, and Ferapenaeus indicus, respectively. The polyunsaturated fatty acids was found 42.60%, 42.29%, and 37.80% in Palaemon karnafuliensis, Metapenaeus monoceros, and Ferapenaeus indicus, respectively. There were nine non-essential and eight essential amino acids found in the dried shrimp products. Glutamine, proline, glycine and alanine were dominated among the non-essential amino acid. Lysine was found a significant amount in the study. All the three dried shrimp products were considered as highly nutritive and less fat value which is considered healthy for the consumers. Asian J. Med. Biol. Res. 2021, 7 (2), 138-146


2020 ◽  
Vol 7 (15) ◽  
pp. 43-57
Author(s):  
Agada Adaeze Bob-Chile ◽  
Peter Uchenna Amadi

This study was carried out to determine the essential oil components, protein qualities, fatty acid composition, and free radical scavenging potentials of leaves of Cola lepidota K. Schum. (Malvaceae) and Irvingia gabonensis (Aubry-Lecomte ex O'Rorke) Baill. (Irvingiaceae) using chromatographic and spectrophotometric methods. Thirty five bioactive components were isolated from C. lepidota leaves with myrcene, phytol, ephedrine, hexadecanoic acid, and 1,14-tetradecanediol as the main compounds while phytol, 2-furancarboxaldehyde, 5-(hydroxymethyl)-, 1-hexadecyne, carotene, and humulene were the predominant components of the I. gabonensis leaves. Leucine and arginine were the predominant essential amino acids, whereas glutamic acid and serine were the main non-essential amino acids in both leaves. The total amino acid (TAA) (70.92 g/100g), total non-essential amino acid (TNEAA) (45.87 g/100 g), and total acidic amino acid (TAAA) (23.01 g/100 g) of C. lepidota were high whereas I. gabonensis recorded higher Total essential amino acid (TEAA) (28.98 g/100 g), total aromatic amino acid (TArAA) (7.21 g/100 g), total branched chain amino acid (TBCAA) (14.28 g/100g), predicted protein efficiency ratios (P-PERs), and essential amino acid index (EAAI). C. lepidota contained 55.72% of unsaturated fatty acids, with predominance of linolenic and linoleic acids, while I. gabonensis produced 74.46% of saturated fatty acids, having myristic, lauric, and palmitic acid as the main compounds. All the radical scavenging potentials of both leaves were concentration dependent and produced higher DPPH, hydrogen peroxide, and ABTS radical scavenging potentials than the standards. This study has thus provided the scientific backing for the inclusion of both leaves for dietary and therapeutic purposes.


1990 ◽  
Vol 259 (4) ◽  
pp. R716-R723 ◽  
Author(s):  
J. L. Beverly ◽  
D. W. Gietzen ◽  
Q. R. Rogers

Microinjection of the dietary limiting essential amino acid (DLAA) into the prepyriform cortex (PPC) increased intake of a diet having an imbalance among the essential amino acids (imbalanced diet) from 50-55% of baseline, when artificial cerebrospinal fluid (aCSF) was injected, to 70-75% of baseline. The increase in intake of the imbalanced diet by DLAA injection became apparent after 3-6 h and was maintained throughout the dark period. Meal size, meal duration, and the number of meals returned to normal after bilateral injections of the DLAA into the PPC of rats fed the imbalanced diet. Injection of the DLAA 30 min before the onset of the dark phase increased intake of imbalanced diet to 70% of baseline intake. When injections of threonine or isoleucine were made 6 and 3 h, respectively, prior to onset of the dark phase, intake of imbalanced diet increased to 85% of baseline intake. Results suggest that some form of processing of the injected DLAA within the PPC is necessary to increase the intake of imbalanced diets.


2021 ◽  
Vol 14 (1) ◽  
pp. 72
Author(s):  
Macus Kuo ◽  
Helen Chen ◽  
Lynn Feun ◽  
Niramol Savaraj

Proline, glutamine, asparagine, and arginine are conditionally non-essential amino acids that can be produced in our body. However, they are essential for the growth of highly proliferative cells such as cancers. Many cancers express reduced levels of these amino acids and thus require import from the environment. Meanwhile, the biosynthesis of these amino acids is inter-connected but can be intervened individually through the inhibition of key enzymes of the biosynthesis of these amino acids, resulting in amino acid starvation and cell death. Amino acid starvation strategies have been in various stages of clinical applications. Targeting asparagine using asparaginase has been approved for treating acute lymphoblastic leukemia. Targeting glutamine and arginine starvations are in various stages of clinical trials, and targeting proline starvation is in preclinical development. The most important obstacle of these therapies is drug resistance, which is mostly due to reactivation of the key enzymes involved in biosynthesis of the targeted amino acids and reprogramming of compensatory survival pathways via transcriptional, epigenetic, and post-translational mechanisms. Here, we review the interactive regulatory mechanisms that control cellular levels of these amino acids for amino acid starvation therapy and how drug resistance is evolved underlying treatment failure.


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