Pharmacologic approaches to amino acid depletion for cancer therapy

2021 ◽  
Author(s):  
Carly S. Wilder ◽  
Zhao Chen ◽  
John DiGiovanni
Keyword(s):  
Amino Acid ◽  
Cancer Therapy ◽  
Amino Acid Depletion

In vivo metabolizable branched poly(ester amide) based on inositol and amino acids as drug nanocarrier for cancer therapy

2021 ◽  
Author(s):  
Jun Wu ◽  
Qi-Juan Yuan ◽  
Li Wang ◽  
Jun Huang ◽  
Wei Zhao
Keyword(s):  
Mechanical Property ◽  
Amino Acids ◽  
Amino Acid ◽  
Cancer Therapy ◽  
Biomedical Applications ◽  
Bioactive Components ◽  
Good Biocompatibility

Amino acid-based poly(ester amide) (PEA) has been utilized for various biomedical applications for its tunable mechanical property, good biocompatibility, and biodegradability. However, bioactive components have rarely been incorporated into the...

scholarly journals The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 675 ◽  
Author(s):  
Bo-Hyun Choi ◽  
Jonathan L. Coloff
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cancer Therapy ◽  
Metabolic Pathways ◽  
Essential Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
Redox Status ◽  
Antioxidant Systems

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.

Target of Rapamycin drives unequal responses to essential amino acid depletion in egg laying

2021 ◽  
Author(s):  
André Nogueira Alves ◽  
Carla M Sgrò ◽  
Matthew D Piper ◽  
Christen K Mirth
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Egg Production ◽  
Essential Amino Acids ◽  
Egg Laying ◽  
Drop Out ◽  
Single Amino Acid ◽  
Amino Acid Depletion ◽  
Holidic Diet ◽  
Related Trait

Nutrition shapes a broad range of life history traits, ultimately impacting animal fitness. A key fitness-related trait, female fecundity is well known to change as a function of diet. In particular, the availability of dietary protein is one of the main drivers of egg production, and in the absence of essential amino acids egg laying declines. However, it is unclear whether all essential amino acids have the same impact on phenotypes like fecundity. Using a holidic diet, we fed adult female D. melanogaster diets that contain all necessary nutrients except one of the 10 essential amino acids and assessed the effects on egg production. For most essential amino acids, depleting a single amino acid induced as rapid a decline in egg production as when there were no amino acids in the diet. However, when either methionine or histidine were excluded from the diet, egg production declined more slowly. Next, we tested whether GCN2 and TOR were involved in this difference in response across amino acids. While mutations in GCN2 did not eliminate the differences in the rates of decline in egg laying among amino acid drop-out diets, we found that inhibiting TOR signalling caused egg laying to decline rapidly for all drop-out diets. TOR signalling does this by regulating the yolk-forming stages of egg chamber development. Our results suggest that amino acids differ in their ability to induce signalling via the TOR pathway. This is important because if phenotypes differ in sensitivity to individual amino acids, this generates the potential for mismatches between the output of a pathway and the animal's true nutritional status.

scholarly journals Proteasome Inhibition in Brassica napus Roots Increases Amino Acid Synthesis to Offset Reduced Proteolysis

2020 ◽  
Vol 61 (6) ◽  
pp. 1028-1040
Author(s):  
Dan Pereksta ◽  
Dillon King ◽  
Fahmida Saki ◽  
Amith Maroli ◽  
Elizabeth Leonard ◽  
...  
Keyword(s):  
Amino Acid ◽  
Brassica Napus ◽  
De Novo ◽  
Metabolic Response ◽  
Sugar Metabolism ◽  
Proteasome Inhibition ◽  
Acid Synthesis ◽  
Amino Acid Synthesis ◽  
Amino Acid Depletion ◽  
Metabolic Activities

Abstract Cellular homeostasis is maintained by the proteasomal degradation of regulatory and misfolded proteins, which sustains the amino acid pool. Although proteasomes alleviate stress by removing damaged proteins, mounting evidence indicates that severe stress caused by salt, metal(oids), and some pathogens can impair the proteasome. However, the consequences of proteasome inhibition in plants are not well understood and even less is known about how its malfunctioning alters metabolic activities. Lethality causes by proteasome inhibition in non-photosynthetic organisms stem from amino acid depletion, and we hypothesized that plants respond to proteasome inhibition by increasing amino acid biosynthesis. To address these questions, the short-term effects of proteasome inhibition were monitored for 3, 8 and 48 h in the roots of Brassica napus treated with the proteasome inhibitor MG132. Proteasome inhibition did not affect the pool of free amino acids after 48 h, which was attributed to elevated de novo amino acid synthesis; these observations coincided with increased levels of sulfite reductase and nitrate reductase activities at earlier time points. However, elevated amino acid synthesis failed to fully restore protein synthesis. In addition, transcriptome analysis points to perturbed abscisic acid signaling and decreased sugar metabolism after 8 h of proteasome inhibition. Proteasome inhibition increased the levels of alternative oxidase but decreased aconitase activity, most sugars and tricarboxylic acid metabolites in root tissue after 48 h. These metabolic responses occurred before we observed an accumulation of reactive oxygen species. We discuss how the metabolic response to proteasome inhibition and abiotic stress partially overlap in plants.

scholarly journals Amino acid depletion and appearance during porcine preimplantation embryo development in vitro

Reproduction ◽  
2005 ◽  
Vol 130 (5) ◽  
pp. 655-668 ◽  
Author(s):  
Paul J Booth ◽  
Peter G Humpherson ◽  
Terry J Watson ◽  
Henry J Leese
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Embryo Development ◽  
Preimplantation Embryos ◽  
Type I ◽  
Preimplantation Embryo Development ◽  
Type Iv ◽  
Stage Of Development ◽  
Amino Acid Depletion

Preimplantation embryos can consume and produce amino acids in a manner dependent upon the stage of development that may be predictive of subsequent viability. In order to examine these relationships in the pig, patterns of net depletion and appearance of amino acids byin vitroproduced porcine preimplantation embryos were examined. Cumulus oocyte complexes derived from slaughterhouse pre-pubertal pig ovaries were matured for 40 h in defined TCM-199 medium (containing PVA) before being fertilised (Day 0) with frozen-thawed semen in Tris–based medium. After 6 h, presumptive zygotes were denuded and cultured in groups of 20, in NCSU-23 medium modified to contain 0.1 mM glutamine plus a mixture of 19 amino acids (aa) at low concentrations (0.02–0.11 mM) (NCSU-23aa). Groups of 2–20 embryos were removed (dependent on stage) on Day 0 (1 cell), Day 1 (two- and four-cells), Day 4 (compact morulae) and Day 6 (blastocysts) and placed in 4 μl NCSU-23aafor 24 h. After incubation, the embryos were removed and the spent media was analysed by HPLC. The net rate of amino acid depletion or appearance varied according to amino acid (P< 0.001) and, apart from serine and histidine, stage of development (P< 0.014). Glycine, isoleucine, valine, phenylalanine, tryptophan, methionine, asparagine, lysine, glutamate and aspartate consistently appeared, whereas threonine, glutamine and arginine were consistently depleted. Five types of stage-dependent trends could be observed: Type I: amino acids having high rates of net appearance on Day 0 that reached a nadir on Day 1 or 4 but subsequently increased by Day 6 (glycine, glutamate); Type II: those that exhibited lower rates of net appearance on Days 0 and 6 compared with the intermediate Days 1 and 4 (isoleucine, valine, phenylalanine, methionine, arginine); Type III: amino acids which showed a continuous fall in net appearance (asparagine, aspartate); Type IV: those that exhibited a steady fall in net depletion from Day 0 to Day 6 (glutamine, threonine); Type V: those following no discernable trend. Analysis of further embryo types indicated that presumptive polyspermic embryos on Day 0 had increased (P< 0.05) net rates of leucine, isoleucine, valine and glutamate appearance, and reduced (P< 0.05) net rates of threonine and glutamine depletion compared with normally inseminated oocytes. These data suggest that the net rates of depletion and uptake of amino acids by pig embryos vary between a) amino acids, b) the day of embryo development and, c) the type of embryos present at a given stage of development. The results also suggested that the net depletion and appearance rates of amino acids by early pig embryos might be more similar to those of the human than those of the mouse and cow.

Sign in / Sign up

Export Citation Format

Share Document