scholarly journals Continuous in vivo metabolism by NMR

2018 ◽  
Author(s):  
Michael T Judge ◽  
Yue Wu ◽  
Fariba Tayyari ◽  
Ayuna Hattori ◽  
John Glushka ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Dynamic Properties ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Lymphoid Leukemia ◽  
Metabolomics Data ◽  
Metabolic Fingerprint

Dense time-series metabolomics data are essential for unraveling the underlying dynamic properties of metabolism. Here we extend high-resolution-magic angle spinning (HR-MAS) to enable continuous in vivo monitoring of metabolism by NMR (CIVM-NMR) and provide analysis tools for these data. First, we reproduced a result in human chronic lymphoid leukemia cells by using isotope-edited CIVM-NMR to rapidly and unambiguously demonstrate unidirectional flux in branched-chain amino acid metabolism. We then collected untargeted CIVM-NMR datasets for Neurospora crassa, a classic multicellular model organism, and uncovered dynamics between central carbon metabolism, amino acid metabolism, energy storage molecules, and lipid and cell wall precursors. Virtually no sample preparation was required to yield a dynamic metabolic fingerprint over hours to days at ~4-min temporal resolution with little noise. CIVM-NMR is simple and readily adapted to different types of cells and microorganisms, offering an experimental complement to kinetic models of metabolism for diverse biological systems.

Glucagon receptor signaling is not required for N-carbamoyl glutamate- and l-citrulline-induced ureagenesis in mice

2020 ◽  
Vol 318 (5) ◽  
pp. G912-G927
Author(s):  
Katrine D. Galsgaard ◽  
Jens Pedersen ◽  
Sasha A. S. Kjeldsen ◽  
Marie Winther-Sørensen ◽  
Elena Stojanovska ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Urea Cycle ◽  
Receptor Signaling ◽  
Glucagon Receptor ◽  
Acetylglutamate Synthase

Hepatic ureagenesis is essential in amino acid metabolism and is importantly regulated by glucagon, but the exact mechanism is unclear. With the aim to identify the steps whereby glucagon both acutely and chronically regulates ureagenesis, we here show, contrary to our hypothesis, that glucagon receptor-mediated activation of ureagenesis is not required when N-acetylglutamate synthase activity and/or N-acetylglutamate levels are sufficient to activate the first step of the urea cycle in vivo.

Renal serine production in vivo: effects of dietary manipulation of serine status

1989 ◽  
Vol 67 (9) ◽  
pp. 1058-1061 ◽  
Author(s):  
John T. Brosnan ◽  
Beatrice Hall
Keyword(s):  
Amino Acids ◽  
Blood Flow ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Dietary Manipulation ◽  
In Vivo Effects ◽  
Crystalline Amino Acids ◽  
Arteriovenous Difference

Renal serine production in rats was quantitated by simultaneously measuring renal blood flow and the renal arteriovenous difference for this amino acid. The rate of synthesis was 0.24 ± 0.02 μmol∙min−1∙100 g−1 in rats fed a diet containing 12% casein. This rate was not altered by the inclusion of an additional 1% serine in the diet for 7 days or by acute infusion of serine, although both protocols increased blood serine by 50%. When rats were fed a diet in which protein was entirely replaced by crystalline amino acids the rate of renal serine production was also 0.25 ±0.05 μmol∙min−1∙100 g−1. Omission of serine or both serine and glycine from this diet did not alter the rate of renal serine synthesis. Renal serine production does not respond to the serine content of the diet.Key words: serine, glycine, kidney, amino acid metabolism.

scholarly journals Reciprocal changes in amino acid metabolism in mammary gland and liver of the lactating rat on starvation and refeeding as indicated by the tissue accumulation of α-amino[1-14C]isobutyrate

1990 ◽  
Vol 268 (3) ◽  
pp. 799-802 ◽  
Author(s):  
A E Tedstone ◽  
V Ilic ◽  
D H Williamson
Keyword(s):  
Amino Acids ◽  
Mammary Gland ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Reciprocal Relationship ◽  
Nutritional State ◽  
Tissue Accumulation

Measurements of the tissue accumulation in vivo and in vitro by hepatocytes and mammary-gland acini of alpha-amino[1-14C]isobutyrate ([1-14C]AIB) were compared in virgin and lactating rats. The results indicate the existence of a reciprocal relationship between mammary gland and liver for AIB accumulation that is dependent on the lactational and the nutritional state of the rat. This suggests that amino acids are preferentially directed to the mammary gland during active lactation.

Changes in Amino Acid Metabolism in vivo with Time after Feeding

1968 ◽  
Vol 32 (12) ◽  
pp. 1440-1447 ◽  
Author(s):  
Toshizo KIMURA ◽  
Kiyoshi ASHIDA
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism

scholarly journals Current Therapeutics, Their Problems, and Sulfur-Containing-Amino-Acid Metabolism as a Novel Target against Infections by “Amitochondriate” Protozoan Parasites

2007 ◽  
Vol 20 (1) ◽  
pp. 164-187 ◽  
Author(s):  
Vahab Ali ◽  
Tomoyoshi Nozaki
Keyword(s):  
Drug Resistance ◽  
Amino Acid ◽  
Trichomonas Vaginalis ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Protozoan Parasites ◽  
Novel Target ◽  
Sulfur Containing

SUMMARY The “amitochondriate” protozoan parasites of humans Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis share many biochemical features, e.g., energy and amino acid metabolism, a spectrum of drugs for their treatment, and the occurrence of drug resistance. These parasites possess metabolic pathways that are divergent from those of their mammalian hosts and are often considered to be good targets for drug development. Sulfur-containing-amino-acid metabolism represents one such divergent metabolic pathway, namely, the cysteine biosynthetic pathway and methionine γ-lyase-mediated catabolism of sulfur-containing amino acids, which are present in T. vaginalis and E. histolytica but absent in G. intestinalis. These pathways are potentially exploitable for development of drugs against amoebiasis and trichomoniasis. For instance, l-trifluoromethionine, which is catalyzed by methionine γ-lyase and produces a toxic product, is effective against T. vaginalis and E. histolytica parasites in vitro and in vivo and may represent a good lead compound. In this review, we summarize the biology of these microaerophilic parasites, their clinical manifestation and epidemiology of disease, chemotherapeutics, the modes of action of representative drugs, and problems related to these drugs, including drug resistance. We further discuss our approach to exploit unique sulfur-containing-amino-acid metabolism, focusing on development of drugs against E. histolytica.

scholarly journals Targeting Amino Acid Metabolic Vulnerabilities in Myeloid Malignancies

2021 ◽  
Vol 11 ◽  
Author(s):  
Livingstone Fultang ◽  
Luciana Gneo ◽  
Carmela De Santo ◽  
Francis J. Mussai
Keyword(s):  
Amino Acid ◽  
Small Molecules ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Expression Patterns ◽  
Tumor Burden ◽  
Murine Models ◽  
Leukemic Stem Cells ◽  
Myeloid Malignancies

Tumor cells require a higher supply of nutrients for growth and proliferation than normal cells. It is well established that metabolic reprograming in cancers for increased nutrient supply exposes a host of targetable vulnerabilities. In this article we review the documented changes in expression patterns of amino acid metabolic enzymes and transporters in myeloid malignancies and the growing list of small molecules and therapeutic strategies used to disrupt amino acid metabolic circuits within the cell. Pharmacological inhibition of amino acid metabolism is effective in inducing cell death in leukemic stem cells and primary blasts, as well as in reducing tumor burden in in vivo murine models of human disease. Thus targeting amino acid metabolism provides a host of potential translational opportunities for exploitation to improve the outcomes for patients with myeloid malignancies.

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