scholarly journals Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Li ◽  
Nianzhi Ning ◽  
Bo Li ◽  
Deyan Luo ◽  
Enqiang Qin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Disease Progression ◽  
Metabolic Disorders ◽  
Acid Metabolism ◽  
Severe Disease ◽  
Essential Amino Acids ◽  
Dynamic Changes ◽  
Metabolic Recovery ◽  
Global Pandemic ◽  
Highly Correlated

COVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in COVID-19 patients, especially their association with disease progression, are still unclear. Here, we systematically analyzed the dynamic changes of the serum metabolome of COVID-19 patients, demonstrating that most of the metabolites did not recover by 1–3 days before discharge. A prominent signature in COVID-19 patients comprised metabolites of amino acids, peptides, and analogs, involving nine essential amino acids, 10 dipeptides, and four N-acetylated amino acids. The levels of 12 metabolites in amino acid metabolism, especially three metabolites of the ornithine cycle, were significantly higher in severe patients than in mild ones, mainly on days 1–3 or 4–6 since onset. Integrating blood metabolomic, biochemical, and cytokine data, we uncovered a highly correlated network, including 6 cytokines, 13 biochemical parameters, and 49 metabolites. Significantly, five ornithine cycle-related metabolites (ornithine, N-acetylornithine, 3-amino-2-piperidone, aspartic acid, and asparagine) highly correlated with “cytokine storms” and coagulation index. We discovered that the ornithine cycle dysregulation significantly correlated with inflammation and coagulation in severe patients, which may be a potential mechanism of COVID-19 pathogenicity. Our study provided a valuable resource for detailed exploration of metabolic factors in COVID-19 patients, guiding metabolic recovery, understanding the pathogenic mechanisms, and creating drugs against SARS-CoV-2 infection.

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.

Free amino acid analysis of untimed and 24-h urine samples compared.

1980 ◽  
Vol 26 (13) ◽  
pp. 1804-1808 ◽  
Author(s):  
M Y Tsai ◽  
J G Marshall ◽  
M W Josephson
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Free Amino ◽  
Metabolic Disorders ◽  
Acid Metabolism ◽  
Reference Interval ◽  
Urine Samples ◽  
Inborn Errors ◽  
Urinary Amino ◽  
Nonketotic Hyperglycinemia

Abstract We measured 11 amino acids in untimed urine samples, to determine whether such samples are suited for use in diagnosis of aminoacidurias. Results for untimed samples varied by as much as 25% more than for 24-h collections when amino acid excretions were expressed in terms of urinary creatinine. Values decreased with increasing age for either type of specimen. Urinary amino acid excretions were also determined with untimed or 24-h samples from patients with cystinuria. Lowe’s syndrome, nonketotic hyperglycinemia, or phenylketonuria. In all cases studied, the amino acids diagnostic of the diseases significantly exceeded the reference interval obtained for 260 control subjects in six age categories. We conclude that untimed urine samples can be used for diagnosis of these inborn errors of amino acid metabolism, but further studies are needed to evaluate their usefulness for other metabolic disorders.

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 Study of the effect of different levels of arginine in feed on broiler chickens

2020 ◽  
Vol 11 (1) ◽  
pp. 908-912 ◽  
Author(s):  
Olga A. Gracheva ◽  
Alizade S. Gasanov ◽  
Damir R. Amirov ◽  
Bulat F. Tamimdarov ◽  
Dina M. Mukhutdinova ◽  
...  
Keyword(s):  
Amino Acids ◽  
Broiler Chickens ◽  
Metabolic Disorders ◽  
Essential Amino Acids ◽  
Feed Additives ◽  
The Body ◽  
Isoleucine Leucine ◽  
Production Experiment ◽  
National University ◽  
Effective Level

Amino acids are the basic structural units of protein molecules in the body. Currently, about 300 amino acids are known, of which 26 are studied best. Amino acids or their derivatives (for example, immune bodies) are part of enzymes, hormones, pigments, and other specific substances that play a crucial role in digestive and metabolic processes. In the process of metabolism, many amino acids are synthesized in the body from other amino acids or compounds, and therefore they are called interchangeable. Amino acids that are not synthesized in the body or are formed in insufficient quantities are called indispensable. According to the content and ratio of essential amino acids, feed proteins are subdivided into full and inferior. Deficiency, absence, or imbalance of essential amino acids in animal diets is accompanied by a deterioration in protein use, metabolic disorders, and decreased productivity. The following amino acids are indispensable; arginine, viburnum, histidine, isoleucine, leucine, lysine, methionine, threonine, tryptophan, phenylalanine. Among the essential amino acids, especially important ones, are those called critical. These are lysine, methionine + cystia, threonine, and tryptophan. A deficiency, absence, or imbalance of essential amino acids in animal diets is accompanied by a deterioration in protein use, metabolic disorders, and decreased productivity. Research and production experiment was conducted within Olenka Poultry Factory LLC and the problematic research laboratory of feed additives of the Department of Animal Feeding and Feed Technology named after P. D. Pshenichny at the National University of Life and Environmental Sciences. The effective level of arginine in compound feed for broilers of the Cobb-500 cross was experimentally determined. The use of compound feed with arginine levels in the first rearing period (1 to 10 days) - 1.28%, in the second (11 to 22 days) - 1.15% and in the third (23 to 42 days) - 1.11% gives the opportunity to get broiler chickens at the age of 42 days, weighing 2.654 kg, at a feed expenditure of 1.78 kg per 1 kg of gain.

Improving the levels of essential amino acids and sulfur metabolites in plants

2005 ◽  
Vol 386 (9) ◽  
Author(s):  
Gad Galili ◽  
Rachel Amir ◽  
Rainer Hoefgen ◽  
Holger Hesse
Keyword(s):  
Amino Acids ◽  
Metabolic Engineering ◽  
Amino Acid Metabolism ◽  
Metabolic Networks ◽  
Acid Metabolism ◽  
Significant Proportion ◽  
Essential Amino Acids ◽  
Plant Foods ◽  
Livestock Feeds ◽  
Low Levels

AbstractPlants represent the major source of food for humans, either directly or indirectly through their use as livestock feeds. Plant foods are not nutritionally balanced because they contain low proportions of a number of essential metabolites, such as vitamins and amino acids, which humans and a significant proportion of their livestock cannot produce on their own. Among the essential amino acids needed in human diets, Lys, Met, Thr and Trp are considered as the most important because they are present in only low levels in plant foods. In the present review, we discuss approaches to improve the levels of the essential amino acids Lys and Met, as well as of sulfur metabolites, in plants using metabolic engineering approaches. We also focus on specific examples for which a deeper understanding of the regulation of metabolic networks in plants is needed for tailor-made improvements of amino acid metabolism with minimal interference in plant growth and productivity.

scholarly journals Dynamic Changes of Plasma Metabolome in Response to Severe Feed Restriction in Pregnant Ewes

Metabolites ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 112 ◽  
Author(s):  
Changzheng Guo ◽  
Yanfeng Xue ◽  
Hossam-eldin Seddik ◽  
Yuyang Yin ◽  
Fan Hu ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Acid Metabolism ◽  
Feed Restriction ◽  
Proline Metabolism ◽  
Dynamic Changes ◽  
Citrate Cycle ◽  
Blood Samples ◽  
Energy Deficiency ◽  
Linoleic Acid Metabolism

Maternal metabolic disorders in ewes induced by energy deficiency have a detrimental effect on the maternal health and lambs. However, the dynamic processes of metabolic disorders are unknown. Therefore, this study attempted to explore the dynamic changes of maternal metabolism based on metabolomics approach during energy deficiency in pregnant ewes. Twenty pregnant Hu sheep were fed a basic diet or a 70% restricted basic diet. The HPLC-MS platform was applied to identify blood metabolites. Principal component analysis of blood samples based on their metabolic profile showed that blood samples of feed restriction group differed after the treatment. In particular, when comparing both groups, there were 120, 129, and 114 differential metabolites at day 5, day 10, and day 114 between the two groups, respectively. Enrichment analysis results showed that four metabolic pathways (glycerophospholipid metabolism, linoleic acid metabolism, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis) at day 5, four metabolic pathways (aminoacyl-tRNA biosynthesis, aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, and citrate cycle) at day 10, and nine metabolic pathways (aminoacyl-tRNA biosynthesis, synthesis and degradation of ketone bodies, glycerophospholipid metabolism, butanoate metabolism, linoleic acid metabolism, citrate cycle, alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine biosynthesis, and arginine and proline metabolism) at day 15 were significantly enriched between the two groups. These findings revealed temporal changes of metabolic disorders in pregnant ewes caused by severe feed restriction, which may provide insights into mitigation measures.

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.

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