scholarly journals Coordination of the Uptake and Metabolism of Amino Acids in Mycobacterium tuberculosis-Infected Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Qingkui Jiang ◽  
Lanbo Shi
Keyword(s):  
Amino Acids ◽  
Mycobacterium Tuberculosis ◽  
Amino Acid ◽  
Macrophage Polarization ◽  
Amino Acid Uptake ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Acid Uptake ◽  
System L ◽  
Uptake And Metabolism

Macrophage polarization to the M1-like phenotype, which is critical for the pro-inflammatory and antimicrobial responses of macrophages against intracellular pathogens, is associated with metabolic reprogramming to the Warburg effect and a high output of NO from increased expression of NOS2. However, there is limited understanding about the uptake and metabolism of other amino acids during M1 polarization. Based on functional analysis of a group of upregulated transporters and enzymes involved in the uptake and/or metabolism of amino acids in Mycobacterium tuberculosis-infected macrophages, plus studies of immune cell activation, we postulate a coherent scheme for amino acid uptake and metabolism during macrophage polarization to the M1-like phenotype. We describe potential mechanisms that the increased arginine metabolism by NOS2 is metabolically coupled with system L transporters LAT1 and LAT2 for the uptake of neutral amino acids, including those that drive mTORC1 signaling toward the M1-like phenotype. We also discuss the underappreciated pleiotropic roles of glutamine metabolism in the metabolic reprogramming of M1-like macrophages. Collectively, our analyses argue that a coordinated amino acid uptake and metabolism constitutes an integral component of the broad metabolic scheme required for macrophage polarization to M1-like phenotype against M. tuberculosis infection. This idea could stimulate future experimental efforts to elucidate the metabolic map of macrophage activation for the development of anti-tuberculosis therapies.

Neutral amino acid influx in developing rabbit blastocysts

1986 ◽  
Vol 251 (2) ◽  
pp. C285-C292 ◽  
Author(s):  
J. E. Bell ◽  
K. E. Begg ◽  
Y. Sin ◽  
J. D. Biggers ◽  
D. J. Benos
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Neutral Amino Acid ◽  
Acid Uptake ◽  
Amino Acid Analogue ◽  
Independent Components ◽  
System A ◽  
Acid Analogue ◽  
System L

The influx of the neutral amino acids glycine, aminoisobutyric acid (AIB), and leucine into rabbit blastocysts was measured. In day 6 postcoitus (pc) embryos, glycine influx was Na+ independent, whereas AIB and leucine influx involved both Na+-dependent and independent components. From days 5 to 7 pc, the leucine and AIB influx remained constant, although the Na+-dependent fraction decreased and the Na+-independent fraction increased with age. None of the Na+-independent influx was inhibited by methylaminoisobutyric acid (MeAIB), an amino acid analogue specific for the system A of neutral amino acid uptake. In addition, MeAIB influx was Na+ independent, implying that system A is not involved in leucine or AIB uptake. All Na+-dependent influx is thus considered to occur via system ASC. System L contributed only to the influx of leucine at days 6 and 7 pc, as measured by inhibition of Na+-independent influx by 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylic acid.

scholarly journals Amino Acid Sensing and Assimilation by the Fungal Pathogen Candida albicans in the Human Host

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 5
Author(s):  
Fitz Gerald S. Silao ◽  
Per O. Ljungdahl
Keyword(s):  
Amino Acids ◽  
Candida Albicans ◽  
Amino Acid ◽  
Fungal Pathogens ◽  
Close Association ◽  
Amino Acid Uptake ◽  
Nutrient Sensing ◽  
Acid Uptake ◽  
Uptake And Metabolism

Nutrient uptake is essential for cellular life and the capacity to perceive extracellular nutrients is critical for coordinating their uptake and metabolism. Commensal fungal pathogens, e.g., Candida albicans, have evolved in close association with human hosts and are well-adapted to using diverse nutrients found in discrete host niches. Human cells that cannot synthesize all amino acids require the uptake of the “essential amino acids” to remain viable. Consistently, high levels of amino acids circulate in the blood. Host proteins are rich sources of amino acids but their use depends on proteases to cleave them into smaller peptides and free amino acids. C. albicans responds to extracellular amino acids by pleiotropically enhancing their uptake and derive energy from their catabolism to power opportunistic virulent growth. Studies using Saccharomyces cerevisiae have established paradigms to understand metabolic processes in C. albicans; however, fundamental differences exist. The advent of CRISPR/Cas9-based methods facilitate genetic analysis in C. albicans, and state-of-the-art molecular biological techniques are being applied to directly examine growth requirements in vivo and in situ in infected hosts. The combination of divergent approaches can illuminate the biological roles of individual cellular components. Here we discuss recent findings regarding nutrient sensing with a focus on amino acid uptake and metabolism, processes that underlie the virulence of C. albicans.

scholarly journals Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 125
Author(s):  
Uğur Kahya ◽  
Ayşe Sedef Köseer ◽  
Anna Dubrovska
Keyword(s):  
Amino Acid ◽  
Cancer Metabolism ◽  
Tumor Imaging ◽  
Redox Homeostasis ◽  
Amino Acid Uptake ◽  
Metabolic Reprogramming ◽  
Tumor Evolution ◽  
Amino Acid Transporters ◽  
Acid Uptake ◽  
Growth And Survival

Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

Gamma-Glutamyl-Amino Acids as Signals for the Hormonal Regulation of Amino Acid Uptake by the Mammary Gland of the Lactating Rat

Neonatology ◽  
1985 ◽  
Vol 48 (4) ◽  
pp. 250-256 ◽  
Author(s):  
Juan R. Viña ◽  
Inmaculada R. Puertes ◽  
Juan B. Montoro ◽  
Guillermo T. Saez ◽  
José Viña
Keyword(s):  
Amino Acids ◽  
Mammary Gland ◽  
Amino Acid ◽  
Hormonal Regulation ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Gamma Glutamyl

scholarly journals Action of growth hormone in vitro on the net uptake and incorporation into protein of amino acids in muscle from intact rabbits given protein-deficient diets

1976 ◽  
Vol 35 (1) ◽  
pp. 1-10 ◽  
Author(s):  
M. R. Turner ◽  
P. J. Reeds ◽  
K. A. Munday
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Amino Acid ◽  
De Novo ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Amino Acid Incorporation ◽  
Acid Incorporation

1. Net amino acid uptake, and incorporation into protein have been measured in vitro in the presence and absence of porcine growth hormone (GH) in muscle from intact rabbits fed for 5 d on low-protein (LP), protein-free (PF) or control diets.2. In muscle from control and LP animals GH had no effect on the net amino acid uptake but stimulated amino acid incorporation into protein, although this response was less in LP animals than in control animals.3. In muscle from PF animals, GH stimulated both amino acid incorporation into protein and the net amino acid uptake, a type of response which also occurs in hypophysectomized animals. The magnitude of the effect of GH on the incorporation of amino acids into protein was reduced in muscle from PF animals.4. The effect of GH on the net amino acid uptake in PF animals was completely blocked by cycloheximide; the uptake effect of GH in these animals was dependent therefore on de novo protein synthesis.5. It is proposed that in the adult the role of growth hormone in protein metabolism is to sustain cellular protein synthesis when there is a decrease in the level of substrate amino acids, similar to that which occurs during a short-term fast or when the dietary protein intake is inadequate.

The uptake of amino acids by mouse cells (strain LS) during growth in batch culture and chemostat culture: the influence of cell growth rate

1967 ◽  
Vol 168 (1013) ◽  
pp. 421-438 ◽  
Keyword(s):  
Amino Acids ◽  
Growth Rate ◽  
Amino Acid ◽  
Cell Growth ◽  
Glutamic Acid ◽  
Batch Culture ◽  
Amino Acid Uptake ◽  
Essential Amino Acids ◽  
Growth Yields ◽  
Acid Uptake

The uptake of thirteen essential amino acids by mouse LS cells in suspension culture was determined by bacteriological assay methods. Chemostat continuous-flow cultures were used to determine the effect of different cell growth rates on the quantitative amino acid requirements for growth. The growth yields of the cells ( Y = g cell dry weight produced/g amino acid utilized) were calculated for each of the essential amino acids. A mixture of the non-essential amino acids, serine, alanine and glycine increased the cell yield from the essential amino acids. The growth yields from nearly all the essential amino acids in batch culture were increased when glutamic acid was substituted for the glutamine in the medium. The growth yields from the amino acids in batch culture were much less at the beginning than at the end of the culture. The highest efficiencies of conversion of amino acids to cell material were obtained by chemostat culture. When glutamic acid largely replaced the glutamine in the medium the conversion of amino acid nitrogen to cell nitrogen was 100 % efficient (that is, the theoretical yield was obtained) at the optimum growth rate (cell doubling time, 43 h). The maximum population density a given amino acid mixture will support can be calculated from the data. It is concluded that in several routinely used tissue culture media the cell growth is limited by the amino acid supply. In batch culture glutamine was wasted by (1) its spontaneous decomposition to pyrrolidone carboxylic acid and ammonia, and (2) its enzymic breakdown to glutamic acid and ammonia, but also glutamine was used less efficiently than glutamic acid. Study of the influence of cell growth rate on amino acid uptake rates per unit mass of cells indicated that a marked change in amino acid metabolism occurred at a specific growth rate of 0.4 day -1 (cell doubling time, 43 h). With decrease in specific growth rate below 0.4 day -1 there was a marked stimulation of amino acid uptake rate per cell and essential amino acids were consumed increasingly for functions other than synthesis of cell material.

scholarly journals Action of insulin and growth hormone on protein synthesis in muscle from non-hypophysectomized rabbits

1971 ◽  
Vol 125 (2) ◽  
pp. 515-520 ◽  
Author(s):  
P. J. Reeds ◽  
K. A. Munday ◽  
M. R. Turner
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Incubation Medium ◽  
Amino Acid Uptake ◽  
Diaphragm Muscle ◽  
Acid Uptake

The separate effects of insulin and growth hormone on the uptake and incorporation of five amino acids into diaphragm muscle from non-hypophysectomized rabbits has been examined. Both growth hormone and insulin, when present in the medium separately, stimulated the incorporation into protein of the amino acids, leucine, arginine, valine, lysine and histidine. Insulin also stimulated amino acid uptake, but growth hormone did not. When insulin and growth hormone were present in the incubation medium together, the uptake and incorporation of valine, the only amino acid studied under these conditions, tended to be greater than the sum of the separate effects of the two hormones.

Amino acid uptake systems in Bacteroides ruminicola

1979 ◽  
Vol 25 (10) ◽  
pp. 1161-1168 ◽  
Author(s):  
Roselynn M. W. Stevenson
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Nitrogen Sources ◽  
Amino Acid Uptake ◽  
Defined Medium ◽  
High Rate ◽  
Transport Systems ◽  
Acid Uptake ◽  
Chemical Structures ◽  
Kinetic Inhibition

Uptake of amino acids by Bacteroides ruminicola was observed in cells grown in a complete defined medium, containing ammonia as the nitrogen source. A high rate of uptake occurred only in fresh medium, as an inhibitory substance, possibly acetate, apparently accumulated during growth. All amino acids except proline were taken up and incorporated into cold trichloroacetic acid precipitable material. Different patterns of incorporation and different responses to 2,4-dinitrophenol and potassium ferricyanide indicated multiple uptake systems were involved. Kinetic inhibition patterns suggested six distinct systems were present for amino acid uptake, with specificities related to the chemical structures of the amino acids. Thus, the failure of free amino acids to act as sole nitrogen sources for growth of B. ruminicola is not due to the absence of transport systems for these compounds.

Acute acidosis inhibits liver amino acid transport: no primary role for the urea cycle in acid-base balance

1994 ◽  
Vol 267 (6) ◽  
pp. F1015-F1020 ◽  
Author(s):  
L. Boon ◽  
P. J. Blommaart ◽  
A. J. Meijer ◽  
W. H. Lamers ◽  
A. C. Schoolwerth
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hepatic Vein ◽  
Amino Acid Transport ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Primary Role ◽  
Urea Synthesis ◽  
Acid Transport ◽  
Acid Base

To examine further the role of the liver in acid-base homeostasis, we studied hepatic amino acid uptake and urea synthesis in rats in vivo during acute acidosis and alkalosis, induced by infusion of 1.8 mmol of HCl or NaHCO3 over 3 h. Amino acids and NH4+ were measured in portal vein, hepatic vein, and aortic plasma, and arteriovenous differences of amino acids and urinary urea and NH4+ excretion were measured. In acidosis, urinary urea excretion was reduced 36% (P < 0.01), whereas urinary NH4+ excretion increased ninefold (P < 0.01), but the sum of urea and NH4+ excretion was unchanged. Total hepatic amino acid uptake, as determined from arteriovenous differences, was decreased by 63% (P < 0.01) in acidosis, with the major effect being noted with alanine and glycine. Only glutamine was released in both acidosis and alkalosis but was not significantly different in the two conditions. Since intracellular concentrations of readily transportable amino acids were not different at low pH despite accelerated protein degradation, these results indicate that hepatic amino acid transport was inhibited markedly and sufficiently to explain the observed decrease in urea synthesis. Total hepatic vein amino acid content was greater in acidosis than alkalosis (P < 0.01). Directly or indirectly, by conversion to glutamine elsewhere, these increased amino acids were degraded in kidney and accounted for the ninefold increase in urinary NH4+ excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Dicarboxylic Amino Acid Uptake in Normal, Friedreich's Ataxia, and Dicarboxylic Aminoaciduria Fibroblasts

1979 ◽  
Vol 6 (2) ◽  
pp. 263-273 ◽  
Author(s):  
S.B. Melancon ◽  
B. Grenier ◽  
L. Dallaire ◽  
M. Potier ◽  
G. Fontaine ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Acid Uptake ◽  
Normal Cells ◽  
Dicarboxylic Amino Acid ◽  
Normal Individuals ◽  
Kinetics Of

SummaryGlutamic and aspartic acid uptake was measured in skin fibroblasts from patients with Friedreich's Ataxia, dicarboxylic aminoaciduria, and normal individuals. The results showed no difference in uptake kinetics of either dicarboxylic amino acids between Friedreich's Ataxia and normal cells, but reduced uptake velocities in dicarboxylic aminoaciduria fibroblasts. Friedreich's Ataxia fibroblasts were, however, less calcium-dependant and more magnesium and phosphate-dependent than controls in glucose-free incubation mixture. This difference might be related to some degree of glucose intolerance by Friedreich's Ataxia fibroblasts in culture.

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