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.

Amino acid metabolism of bovine blastocysts derived from parthenogenetically activated or in vitro fertilized oocytes

1998 ◽  
Vol 10 (3) ◽  
pp. 279 ◽  
Author(s):  
Y. G. Jung ◽  
T. Sakata ◽  
E. S. Lee ◽  
Y. Fukui
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Culture Medium ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
Fluid Medium ◽  
Vitro Fertilization ◽  
Oviduct Fluid

The uptake and synthesis of 19 amino acids by fresh or frozen–thawed bovine blastocysts produced by parthenogenesis (PT) or in vitro fertilization (IVF) were compared in the present study. Fresh blastocysts, 180 h after IVF or PT activation, and frozen–thawed blastocysts, 168 h old and cultured for 12 h post-thawing, were cultured in synthetic oviduct fluid medium (SOFM) containing polyvinyl alcohol (PVA) with both essential and non-essential amino acids (EAA and NEAA, respectively) (Medium 1: M1) or SOFM containing PVA with only EAA (Medium 2: M2). In Experiment 1, when fresh or frozen–thawed PT blastocysts were cultured in M1, the uptake of glutamate (in fresh only), aspartate and arginine, and the synthesis of glutamine and alanine were significantly enhanced. In the culture with M2, serine, asparagine, glutamate, glutamine, glycine, arginine and alanine were significantly taken up. It was found that the glutamine concentrations was significantly higher (P < 0.001) in the culture medium drops containing embryos than in the drops without embryos. In Experiment 2, when PT blastocysts were cultured in M1, the uptake of aspartate and synthesis of alanine were greater (P < 0.01) than those by IVF blastocysts. When M2 was used, a significant (P < 0.01) production of serine, asparagine, glutamate, glutamine and alanine, and the uptake of arginine by PT blastocysts were observed. In Experiment 3, when IVF blastocysts were cultured in M1, fresh blastocysts depleted more aspartate and glutamate, and produced more glutamine and alanine than frozen–thawed blastocysts. When cultured in M2, frozen–thawed blastocysts depleted more threonine (P < 0.01) than fresh blastocysts. These results indicate that the uptake and synthesis of amino acids were different in fresh or frozen–thawed bovine blastocysts derived from PT or IVF. These differences in amino acid metabolism may be related to the viability of the blastocysts.

scholarly journals The case for regulating indispensable amino acid metabolism: the branched-chain α-keto acid dehydrogenase kinase-knockout mouse

2006 ◽  
Vol 400 (1) ◽  
Author(s):  
Susan M. Hutson
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
The Body ◽  
Keto Acid ◽  
Acid Dehydrogenase ◽  
Indispensable Amino Acid ◽  
Branched Chain

BCAAs (branched-chain amino acids) are indispensable (essential) amino acids that are required for body protein synthesis. Indispensable amino acids cannot be synthesized by the body and must be acquired from the diet. The BCAA leucine provides hormone-like signals to tissues such as skeletal muscle, indicating overall nutrient sufficiency. BCAA metabolism provides an important transport system to move nitrogen throughout the body for the synthesis of dispensable (non-essential) amino acids, including the neurotransmitter glutamate in the central nervous system. BCAA metabolism is tightly regulated to maintain levels high enough to support these important functions, but at the same time excesses are prevented via stimulation of irreversible disposal pathways. It is well known from inborn errors of BCAA metabolism that dysregulation of the BCAA catabolic pathways that leads to excess BCAAs and their α-keto acid metabolites results in neural dysfunction. In this issue of Biochemical Journal, Joshi and colleagues have disrupted the murine BDK (branched-chain α-keto acid dehydrogenase kinase) gene. This enzyme serves as the brake on BCAA catabolism. The impaired growth and neurological abnormalities observed in this animal show conclusively the importance of tight regulation of indispensable amino acid metabolism.

scholarly journals Oncology Therapeutics Targeting the Metabolism of Amino Acids

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1904 ◽  
Author(s):  
Nefertiti Muhammad ◽  
Hyun Min Lee ◽  
Jiyeon Kim
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
De Novo ◽  
Essential Amino Acids ◽  
Cancer Cell Proliferation ◽  
Ros Scavenging ◽  
Cancer Proliferation ◽  
Extracellular Environment

Amino acid metabolism promotes cancer cell proliferation and survival by supporting building block synthesis, producing reducing agents to mitigate oxidative stress, and generating immunosuppressive metabolites for immune evasion. Malignant cells rewire amino acid metabolism to maximize their access to nutrients. Amino acid transporter expression is upregulated to acquire amino acids from the extracellular environment. Under nutrient depleted conditions, macropinocytosis can be activated where proteins from the extracellular environment are engulfed and degraded into the constituent amino acids. The demand for non-essential amino acids (NEAAs) can be met through de novo synthesis pathways. Cancer cells can alter various signaling pathways to boost amino acid usage for the generation of nucleotides, reactive oxygen species (ROS) scavenging molecules, and oncometabolites. The importance of amino acid metabolism in cancer proliferation makes it a potential target for therapeutic intervention, including via small molecules and antibodies. In this review, we will delineate the targets related to amino acid metabolism and promising therapeutic approaches.

scholarly journals Multi-omics data reveal genes that are relevant for muscular amino acids in the common carp

2020 ◽  
Author(s):  
Youxiu Zhu ◽  
Hanyuan Zhang ◽  
Peng Xu ◽  
Zixia Zhao ◽  
Jianxin Feng ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Common Carp ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
Muscle Tissues ◽  
The Common ◽  
Branched Chain ◽  
Amino Acid Contents

Abstract Background Fish muscular amino acids are a series of essential nutrients that embrace essential amino acids, branched-chain amino acids and flavorous amino acids. Previous studies have found that amino acids have important physiological effects on fish growth and development, as they are involved in maintaining nitrogen balance and in the formation of enzymes and hormones. Amino acids, such as aspartic acid, glutamic acid, glycine and alanine, that can have a significant effect on fish umami taste are called flavorous amino acids. Nevertheless, the studies on the genetic mechanisms of amino acid metabolism in the common carp (Cyprinus carpio) are still limited. Results The purpose of this study was to examine the divergent patterns at the genomic, transcriptomic and epigenomic levels in fish with different amino acid contents. Genome-wide association analysis using 195 individuals of common carp was conducted, and 62 genes were identified to be associated with glycine, proline, and tyrosine content. RNA-Seq of samples with extreme contents of essential amino acids, branched-chain amino acids and flavorous amino acids was applied using brain, liver and muscle tissues, resulting in 1,643 differentially expressed genes. Whole-genome bisulfite sequencing identified 3,108 genes with differentially methylated promoters. Through the enrichment analysis of transcriptome and DNA methylation results, we screened out a series of enriched pathways associated with amino acid metabolism, including various categories of pathways spanning growth regulation, lipid metabolism, the citrate cycle and other signaling pathways. Integrated studies demonstrated prominent correlations between DGE and DMP for amino acid contents trait in brain and muscle tissues. Conclusion In summary, the multi-omics data revealed candidate genes and pathways correlated with amino acid metabolism. These results will promote the process of the genomic selection and breeding strategy in muscular amino acid contents of fish.

scholarly journals Multi-omics data reveal genes that are relevant for muscular amino acids in the common carp

2021 ◽  
Author(s):  
Youxiu Zhu ◽  
Hanyuan Zhang ◽  
Peng Xu ◽  
Zixia Zhao ◽  
Jianxin Feng ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Common Carp ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
Muscle Tissues ◽  
The Common ◽  
Branched Chain ◽  
Amino Acid Contents

Abstract Background: Fish muscular amino acids are a series of essential nutrients that embrace essential amino acids, branched-chain amino acids and flavorous amino acids. Previous studies have found that amino acids have important physiological effects on fish growth and development, as they are involved in maintaining nitrogen balance and in the formation of enzymes and hormones. Amino acids, such as aspartic acid, glutamic acid, glycine and alanine, that can have a significant effect on fish umami taste are called flavorous amino acids. Nevertheless, the studies on the genetic mechanisms of amino acid metabolism in the common carp (Cyprinus carpio) are still limited.Results: The purpose of this study was to examine the divergent patterns at the genomic, transcriptomic and epigenomic levels in fish with different amino acid contents. Genome-wide association analysis using 195 individuals of common carp was conducted, and 62 genes were identified to be associated with glycine, proline, and tyrosine content. RNA-Seq of samples with extreme contents of essential amino acids, branched-chain amino acids and flavorous amino acids was applied using brain, liver and muscle tissues, resulting in 1,643 differentially expressed genes. Whole-genome bisulfite sequencing identified 3,108 genes with differentially methylated promoters. Through the enrichment analysis of transcriptome and DNA methylation results, we screened out a series of enriched pathways associated with amino acid metabolism, including various categories of pathways spanning growth regulation, lipid metabolism, the citrate cycle and other signaling pathways. Integrated studies demonstrated prominent correlations between DGE and DMP for amino acid contents trait in brain and muscle tissues.Conclusions: In summary, the multi-omics data revealed candidate genes and pathways correlated with amino acid metabolism. These results will promote the process of the genomic selection and breeding strategy in muscular amino acid contents of fish.

scholarly journals Oncology Therapeutics Targeting the Metabolism of Amino Acids

2020 ◽  
Author(s):  
Nefertiti Muhammad ◽  
Hyun Min Lee ◽  
Jiyeon Kim
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
De Novo ◽  
Essential Amino Acids ◽  
Cancer Cell Proliferation ◽  
Ros Scavenging ◽  
Cancer Proliferation ◽  
Extracellular Environment

Amino acid metabolism promotes cancer cell proliferation and survival by supporting building block synthesis, producing reducing agents to mitigate oxidative stress, and generating immunosuppressive metabolites for immune evasion. Malignant cells rewire amino acid metabolism to maximize their access to nutrients. Amino acid transporter expression is upregulated to acquire amino acids from the extracellular environment. Under nutrient depleted conditions, macropinocytosis can be activated where proteins from the extracellular environment are engulfed and degraded into the constituent amino acids. The demand for non-essential amino acids (NEAAs) can be met through de novo synthesis pathways. Cancer cells can alter various signaling pathways to boost amino acid usage for the generation of nucleotides, reactive oxygen species (ROS) scavenging molecules and oncometabolites. The importance of amino acid metabolism in cancer proliferation makes it a potential target for therapeutic intervention, including via small molecules and antibodies. In this review, we will delineate the targets related to amino acid metabolism and promising therapeutic approaches.

scholarly journals Comprehensive transcriptome and metabolome profiling reveal metabolic mechanisms of Nitraria sibirica Pall. to salt stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huanyong Li ◽  
Xiaoqian Tang ◽  
Xiuyan Yang ◽  
Huaxin Zhang
Keyword(s):  
Salt Stress ◽  
Amino Acid ◽  
Salt Tolerance ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Sulfur Metabolism ◽  
Enrichment Analysis ◽  
Extracellular Region ◽  
Nitraria Sibirica

AbstractNitraria sibirica Pall., a typical halophyte that can survive under extreme drought conditions and in saline-alkali environments, exhibits strong salt tolerance and environmental adaptability. Understanding the mechanism of molecular and physiological metabolic response to salt stress of plant will better promote the cultivation and use of halophytes. To explore the mechanism of molecular and physiological metabolic of N. sibirica response to salt stress, two-month-old seedlings were treated with 0, 100, and 400 mM NaCl. The results showed that the differentially expressed genes between 100 and 400 mmol L−1 NaCl and unsalted treatment showed significant enrichment in GO terms such as binding, cell wall, extemal encapsulating structure, extracellular region and nucleotide binding. KEGG enrichment analysis found that NaCl treatment had a significant effect on the metabolic pathways in N. sibirica leaves, which mainly including plant-pathogen interaction, amino acid metabolism of the beta alanine, arginine, proline and glycine metabolism, carbon metabolism of glycolysis, gluconeogenesis, galactose, starch and sucrose metabolism, plant hormone signal transduction and spliceosome. Metabolomics analysis found that the differential metabolites between the unsalted treatment and the NaCl treatment are mainly amino acids (proline, aspartic acid, methionine, etc.), organic acids (oxaloacetic acid, fumaric acid, nicotinic acid, etc.) and polyhydric alcohols (inositol, ribitol, etc.), etc. KEGG annotation and enrichment analysis showed that 100 mmol L−1 NaCl treatment had a greater effect on the sulfur metabolism, cysteine and methionine metabolism in N. sibirica leaves, while various amino acid metabolism, TCA cycle, photosynthetic carbon fixation and sulfur metabolism and other metabolic pathways have been significantly affected by 400 mmol L−1 NaCl treatment. Correlation analysis of differential genes in transcriptome and differential metabolites in metabolome have found that the genes of AMY2, BAM1, GPAT3, ASP1, CML38 and RPL4 and the metabolites of L-cysteine, proline, 4-aminobutyric acid and oxaloacetate played an important role in N. sibirica salt tolerance control. This is a further improvement of the salt tolerance mechanism of N. sibirica, and it will provide a theoretical basis and technical support for treatment of saline-alkali soil and the cultivation of halophytes.

Biochemische Aspekte des Aminosäuren-Stoffwechsels bei Psoriasis vulgaris / Biochemical Aspects of Amino Acid Metabolism in Psoriasis vulgaris

1973 ◽  
Vol 28 (7-8) ◽  
pp. 449-451 ◽  
Author(s):  
G. Peter ◽  
H. Angst ◽  
U. Koch
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Free Amino Acids ◽  
Free Amino ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Psoriasis Vulgaris ◽  
Normal Subjects ◽  
Pathological Process

Free and protein-bound amino acids in serum and scales were investigated. In serum the bound amino acids of psoriatics are significantly higher with exception of Pro, Met, Tyr and Phe in contrast to normal subjects. For free amino acids the differences between normal subjects and psoriatics found in serum and scales are not significant. Results are discussed in relation to the single amino acids and the biochemical correlations are outlined which takes the pathological process as a basis.

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