Longitudinal metabolomics profiling of serum amino acids in rotenone-induced Parkinson's mouse model

Protein synthesis was measured in rat diaphragms incubated with serum amino acids + 0.35 mM L-[2,6-3H]tyrosine and different energy-yielding substrates. Muscles incubated with 5.5 mM glucose (with or without actinomycin D) synthesized more protein than those incubated with 11 mM pyruvate or 11 mM lactate. Tissue ATP decreased during incubation with lactate, but pyruvate maintained ATP, ADP, and creatine phosphate as well as glucose. Glucose 6-phosphate decreased in muscles incubated in glucose-free media. 14CO2 production from substrates was [1-14C]pyruvate greater than [1-14C]lactate greater than [3,4-14C]glucose. Intracellular lactate/pyruvate was measured to assess cytoplasmic free NADH/NAD+; the effect of different media on these ratios was lactate greater than glucose = lactate + pyruvate greater than pyruvate + glucose greater than pyruvate. Lactate + pyruvate (8.8 + 2.2 mM) supported protein synthesis better than pyruvate and as well as glucose. Adding glucose to pyruvate accelerated protein synthesis and increased NADH/NAD+. Iodoacetate (0.1 mM) inhibited glycolytic NAD reduction and abolished the stimulatory effect of glucose on protein synthesis in the presence of pyruvate. Supplementation of pyruvate media with 1 mM leucine or isoleucine stimulated protein synthesis, but beta-hydroxybutyrate, malate, alpha-ketoisocaproate, and all other amino acids were ineffective. The cytoplasmic redox potential may act as a translational modulator of protein synthesis in skeletal muscle.

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Effect of protein restriction on15N transfer from dietary [15N]alanine and [15N]Spirulina platensisinto urea

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.281.2.e349 ◽

2001 ◽

Vol 281 (2) ◽

pp. E349-E356 ◽

Cited By ~ 2

Author(s):

Mazen J. Hamadeh ◽

L. John Hoffer

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Test Meal ◽

High Protein Diet ◽

Normal Subjects ◽

Insulin Dependent Diabetes Mellitus ◽

Protein Restriction ◽

Dependent Diabetes Mellitus ◽

Serum Amino Acids ◽

Normal Men

Six normal men consumed a mixed test meal while adapted to high (1.5 g · kg−1· day−1) and low (0.3 g · kg−1· day−1) protein intakes. They completed this protocol twice: when the test meals included 3 mg/kg of [15N]alanine ([15N]Ala) and when they included 30 mg/kg of intrinsically labeled [15N] Spirulina platensis([15N]SPI). Six subjects with insulin-dependent diabetes mellitus (IDDM) receiving conventional insulin therapy consumed the test meal with added [15N]Ala while adapted to their customary high-protein diet. Protein restriction increased serum alanine, glycine, glutamine, and methionine concentrations and reduced those of leucine. Whether the previous diet was high or low in protein, there was a similar increase in serum alanine, methionine, and branched-chain amino acid concentrations after the test meal and a similar pattern of15N enrichment in serum amino acids for a given tracer. When [15N]Ala was included in the test meal,15N appeared rapidly in serum alanine and glutamine, to a minor degree in leucine and isoleucine, and not at all in other circulating amino acids. With [15N]SPI, there was a slow appearance of the label in all serum amino acids analyzed. Despite the different serum amino acid labeling, protein restriction reduced the postmeal transfer of dietary15N in [15N]Ala or [15N]SPI into [15N]urea by similar amounts (38 and 43%, respectively, not significant). The response of the subjects with IDDM was similar to that of the normal subjects. Information about adaptive reductions in dietary amino acid catabolism obtained by adding [15N]Ala to a test meal appears to be equivalent to that obtained using an intrinsically labeled protein tracer.

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Complex behavioral and synaptic effects of dietary branched chain amino acids in a mouse model of amyotrophic lateral sclerosis

Molecular Nutrition & Food Research ◽

10.1002/mnfr.201000296 ◽

2011 ◽

Vol 55 (4) ◽

pp. 541-552 ◽

Cited By ~ 2

Author(s):

Aldina Venerosi ◽

Alberto Martire ◽

Angela Rungi ◽

Massimo Pieri ◽

Antonella Ferrante ◽

...

Keyword(s):

Amino Acids ◽

Amyotrophic Lateral Sclerosis ◽

Mouse Model ◽

Branched Chain Amino Acids ◽

Branched Chain ◽

Synaptic Effects ◽

Lateral Sclerosis

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IRW and IQW Reduce Colitis-Associated Cancer Risk by Alleviating DSS-Induced Colonic Inflammation

BioMed Research International ◽

10.1155/2019/6429845 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Yong Ma ◽

Hongmei Jiang ◽

Jun Fang ◽

Gang Liu

Keyword(s):

Amino Acids ◽

Intestinal Inflammation ◽

Great Influence ◽

Basal Diet ◽

Immune Defense ◽

Inflammatory Factors ◽

Adaptation Period ◽

Serum Samples ◽

Serum Amino Acids ◽

Inflammatory Bowel

Background and Objective. Bioactive peptides exert great influence in animals and human health by targeting gastrointestinal tracts. The colitis model of mice was induced by dextran sulfate sodium (DSS). Thirty-two 8-week-old mice weighing 23 g on average were randomly assigned to four groups of 8 each: mice fed basal diet (CON), mice fed basal diet with 5% DSS (DSS), mice fed 0.03% IRW with 5% DSS (IRW-DSS), and mice fed 0.03% IRW with 5% DSS (IQW-DSS). After an adaptation period of 3 days, on day 8, all mice were slaughtered. Serum samples were collected to determine the level of amino acids; colonic tissue was quick-frozen for the determination of gene expression. Methods. The aim of this study was to assess the ability of two kinds of peptides (IRW and IQW) to repair intestinal inflammatory in the DSS-induced model in accordance with serum amino acids and intestinal inflammatory factors. Results. The results demonstrated that the addition of IRW and IQW had a mitigating effect on DSS-induced intestinal inflammation. The level of Asp decreased in the serum of mice supplemented with IRW-DSS (P<0.05), and IQW enhanced the level of Leu, but lowered the level of Ser (P<0.05). IQW and IRW addition reduced the level of TNF-α and IL-17 (P<0.05). No other significant effects were observed. Conclusions. The present study demonstrated that intracolic administration of IRW and IQW might be a novel option for preventing inflammatory bowel disease via regulating the level of serum amino acid and enhancing the intestinal immune defense.

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Targeted Metabolomic Analysis of a Mucopolysaccharidosis IIIB Mouse Model Reveals an Imbalance of Branched-Chain Amino Acid and Fatty Acid Metabolism

International Journal of Molecular Sciences ◽

10.3390/ijms21124211 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4211 ◽

Cited By ~ 2

Author(s):

Valeria De Pasquale ◽

Marianna Caterino ◽

Michele Costanzo ◽

Roberta Fedele ◽

Margherita Ruoppolo ◽

...

Keyword(s):

Amino Acids ◽

Fatty Acid ◽

Amino Acid ◽

Mouse Model ◽

Molecular Mechanisms ◽

Clinical Manifestations ◽

Neurological Impairment ◽

Genetic Mutation ◽

Inherited Disorders ◽

Branched Chain

Mucopolysaccharidoses (MPSs) are inherited disorders of the glycosaminoglycan (GAG) metabolism. The defective digestion of GAGs within the intralysosomal compartment of affected patients leads to a broad spectrum of clinical manifestations ranging from cardiovascular disease to neurological impairment. The molecular mechanisms underlying the progression of the disease downstream of the genetic mutation of genes encoding for lysosomal enzymes still remain unclear. Here, we applied a targeted metabolomic approach to a mouse model of PS IIIB, using a platform dedicated to the diagnosis of inherited metabolic disorders, in order to identify amino acid and fatty acid metabolic pathway alterations or the manifestations of other metabolic phenotypes. Our analysis highlighted an increase in the levels of branched-chain amino acids (BCAAs: Val, Ile, and Leu), aromatic amino acids (Tyr and Phe), free carnitine, and acylcarnitines in the liver and heart tissues of MPS IIIB mice as compared to the wild type (WT). Moreover, Ala, Met, Glu, Gly, Arg, Orn, and Cit amino acids were also found upregulated in the liver of MPS IIIB mice. These findings show a specific impairment of the BCAA and fatty acid catabolism in the heart of MPS IIIB mice. In the liver of affected mice, the glucose-alanine cycle and urea cycle resulted in being altered alongside a deregulation of the BCAA metabolism. Thus, our data demonstrate that an accumulation of BCAAs occurs secondary to lysosomal GAG storage, in both the liver and the heart of MPS IIIB mice. Since BCAAs regulate the biogenesis of lysosomes and autophagy mechanisms through mTOR signaling, impacting on lipid metabolism, this condition might contribute to the progression of the MPS IIIB disease.

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