scholarly journals Heptanoate as a Neural Fuel: Energetic and Neurotransmitter Precursors in Normal and Glucose Transporter I-Deficient (G1D) Brain

2012 ◽  
Vol 33 (2) ◽  
pp. 175-182 ◽  
Author(s):  
Isaac Marin-Valencia ◽  
Levi B Good ◽  
Qian Ma ◽  
Craig R Malloy ◽  
Juan M Pascual
Keyword(s):  
Mass Spectrometry ◽  
Glucose Transporter ◽  
Tricarboxylic Acid Cycle ◽  
Gas Chromatography Mass Spectrometry ◽  
Resonance Spectroscopy ◽  
Type I ◽  
Acetyl Coa ◽  
Chromatography Mass Spectrometry ◽  
Neurotransmitter Precursors ◽  
The Brain

It has been postulated that triheptanoin can ameliorate seizures by supplying the tricarboxylic acid cycle with both acetyl-CoA for energy production and propionyl-CoA to replenish cycle intermediates. These potential effects may also be important in other disorders associated with impaired glucose metabolism because glucose supplies, in addition to acetyl-CoA, pyruvate, which fulfills biosynthetic demands via carboxylation. In patients with glucose transporter type I deficiency (G1D), ketogenic diet fat (a source only of acetyl-CoA) reduces seizures, but other symptoms persist, providing the motivation for studying heptanoate metabolism. In this work, metabolism of infused [5,6,7-13C3]heptanoate was examined in the normal mouse brain and in G1D by 13C-nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). In both groups, plasma glucose was enriched in 13C, confirming gluconeogenesis from heptanoate. Acetyl-CoA and glutamine levels became significantly higher in the brain of G1D mice relative to normal mice. In addition, brain glutamine concentration and 13C enrichment were also greater when compared with glutamate in both animal groups, suggesting that heptanoate and/or C5 ketones are primarily metabolized by glia. These results enlighten the mechanism of heptanoate metabolism in the normal and glucosedeficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism.

Use of mass isotopomer distributions in secreted lipids to sample lipogenic acetyl-CoA pool in vivo in humans

1991 ◽  
Vol 261 (4) ◽  
pp. E479-E486 ◽  
Author(s):  
M. K. Hellerstein ◽  
C. Kletke ◽  
S. Kaempfer ◽  
K. Wu ◽  
C. H. Shackleton
Keyword(s):  
Mass Spectrometry ◽  
De Novo ◽  
Density Lipoprotein ◽  
Gas Chromatography Mass Spectrometry ◽  
Invasive Technique ◽  
Acetyl Coa ◽  
Precursor Pool ◽  
Chromatography Mass Spectrometry ◽  
Mass Isotopomer

Measurement of hepatic fatty acid (FA) and cholesterol synthesis has been limited by lack of access to the precursor pool, cytosolic acetyl-CoA. We present a method for inferring the enrichment of the true hepatic lipogenic precursor pool in humans using the frequency distribution of mass isotopomers within enriched circulating polymers of acetyl-CoA [very low-density lipoprotein (VLDL)-palmitate, VLDL-stearate]. Human subjects were infused intravenously (n = 16) with [1-13C]- or [2-13C]acetate. Oral sulfamethoxazole (SMX) was administered concurrently, and the acetylated conjugate (SMX acetate) was used to estimate independently the hepatic cytosolic acetyl-CoA enrichment. Isotopomer frequencies in VLDL-FA were determined by gas chromatography-mass spectrometry, whereas high-performance liquid chromatography-mass spectrometry was used to measure enrichments in SMX acetate. Based on the excess M2/excess M1 ratio in VLDL-FA, calculated acetyl-CoA enrichments were 5.59 +/- 0.33 molar percent excess (MPE), whereas SMX acetate enrichments were 5.38 +/- 0.31 MPE (the 2 methods were not significantly different). Mass isotopomer-calculated and SMX acetate-measured estimates of acetyl-CoA enrichments correlated very closely in individual subjects (r2 = 0.93; P less than 0.0001). De novo hepatic lipogenesis can be measured using isotopomer-calculated precursor enrichments compared with measured incorporation in specific isotopomers of VLDL-FA. In summary, excess isotopomer frequencies in secreted lipids provide a non-invasive technique for estimating hepatic cytosolic acetyl-CoA enrichments in humans in vivo and correlate closely with enrichments observed using the xenobiotic probe technique. Isotopomeric distributions represent a new strategy for accurate measurement of macromolecule synthesis that may be applicable to other classes of molecules besides lipids.

The role of metabolomics in personalized medicine for diabetes

2021 ◽  
Author(s):  
Shamiha Chowdhury ◽  
Sultan Mohammed Faheem ◽  
Shaik Sarfaraz Nawaz ◽  
Khalid Siddiqui
Keyword(s):  
Mass Spectrometry ◽  
Personalized Medicine ◽  
Diabetes Management ◽  
Gas Chromatography Mass Spectrometry ◽  
Resonance Spectroscopy ◽  
Liquid Chromatography Mass Spectrometry ◽  
Hydroxybutyric Acid ◽  
Chromatography Mass Spectrometry ◽  
Branch Chain Amino

Metabolomics is rapidly evolving omics technology in personalized medicine, it offers a new avenue for identification of multiple novel metabolic mediators of impaired glucose tolerance and dysglycemia. Liquid chromatography–mass spectrometry, gas chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy are most commonly used analytical methods in the field of metabolomics. Recent evidences showed that metabolomic profiles are link to the incidence of diabetes. In this review, an overview of metabolomics studies in diabetes revealed several diabetes-associated metabolites including 1,5 anhydroglycitol, branch chain amino acids, glucose, α-hydroxybutyric acid, 3-hydroundecanoyl-carnitine and phosphatidylcholine that could be potential biomarkers associated with diabetes. These identified metabolites can be used to develop personalized prognostics and diagnostic, and help in diabetes management.

scholarly journals Metabolic phenotyping of a model of adipocyte differentiation

2009 ◽  
Vol 39 (2) ◽  
pp. 109-119 ◽  
Author(s):  
Lee D. Roberts ◽  
Sam Virtue ◽  
Antonio Vidal-Puig ◽  
Andrew W. Nicholls ◽  
Julian L. Griffin
Keyword(s):  
Mass Spectrometry ◽  
Fatty Acid ◽  
Cell Line ◽  
Tca Cycle ◽  
Acid Synthesis ◽  
Metabolic Phenotype ◽  
Gas Chromatography Mass Spectrometry ◽  
Resonance Spectroscopy ◽  
Polyamine Biosynthesis ◽  
Chromatography Mass Spectrometry

The 3T3-L1 murine cell line is a robust and widely used model for the study of adipogenesis and processes occurring in mature adipocytes. The fibroblastic like cells can be induced by hormones to differentiate into mature adipocytes. In this study, the metabolic phenotype associated with differentiation of the 3T3-L1 cell line has been studied using gas chromatography-mass spectrometry, 1H nuclear magnetic resonance spectroscopy, liquid chromatography-mass spectrometry, direct infusion-mass spectrometry, and 13C substrate labeling in conjunction with multivariate statistics. The changes in metabolite concentrations at distinct periods during differentiation have been defined including alterations in the TCA cycle, glycolysis, the production of odd chain fatty acids by α-oxidation, fatty acid synthesis, fatty acid desaturation, polyamine biosynthesis, and trans-esterification to produce complex lipids. The metabolic changes induced during differentiation of the 3T3-L1 cell line were then compared with the metabolic differences between pre- and postdifferentiation primary adipocytes. These metabolic alterations reflect the changing role of the 3T3-L1 cells during differentiation, as well as possibly providing metabolic triggers to stimulate the processes which occur during differentiation.

Cysteine Conjugate β-Lyase-Dependent Metabolism of Compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene) in Human Subjects Anesthetized with Sevoflurane and in Rats Given Compound A 

1998 ◽  
Vol 88 (3) ◽  
pp. 611-618 ◽  
Author(s):  
Ramaswamy A. Iyer ◽  
Edward J. Frink ◽  
Thomas J. Ebert ◽  
M. W. Anders
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Human Subjects ◽  
Gas Chromatography Mass Spectrometry ◽  
Resonance Spectroscopy ◽  
Metabolite Formation ◽  
Rat Urine ◽  
Compound A ◽  
Chromatography Mass Spectrometry ◽  
Human Volunteers

Background Sevoflurane undergoes Baralyme- or soda lime-catalyzed degradation in the anesthesia circuit to yield compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluroro-1-propene), which is nephrotoxic in rats and undergoes metabolism via the cysteine conjugate beta-lyase pathway in those animals. The objective of these experiments was to test the hypothesis that compound A undergoes beta-lyase-dependent metabolism in humans. Methods Human volunteers were anesthetized with sevoflurane (1.25 minimum alveolar concentration, 3%, 2 l/min, 8 h) and thereby exposed to compound A. Urine was collected at 24-h intervals for 72 h after anesthesia. Rats, which served as a positive control, were given compound A intraperitoneally, and urine was collected for 24 h afterward. Human and rat urine samples were analyzed by 19F nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry for the presence of compound A metabolites. Results Analysis of human and rat urine showed the presence of the compound A metabolites S-[2(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-N-acetyl-L- cysteine, (E)- and (Z)-S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-N-acetyl- L-cysteine, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid, 3,3,3-trifluorolactic acid, and inorganic fluoride. The presence of 2-(fluoromethoxy)3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in human urine was confirmed by gas chromatography-mass spectrometry. Conclusions The formation of compound A-derived mercapturates shows that compound A undergoes glutathione S-conjugate formation. The identification of 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in the urine of humans anesthetized with sevoflurane shows that compound A undergoes beta-lyase-dependent metabolism. Metabolite formation was qualitatively similar in both human volunteers anesthetized with sevoflurane, and thereby exposed to compound A, and in rats given compound A, indicating that compound A is metabolized by the beta-lyase pathway in both species.

scholarly journals Metabolic Reprogramming and Risk Stratification of Hepatocellular Carcinoma Studied by Using Gas Chromatography–Mass Spectrometry-Based Metabolomics

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 231
Author(s):  
Chengnan Fang ◽  
Hui Wang ◽  
Zhikun Lin ◽  
Xinyu Liu ◽  
Liwei Dong ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Hepatocellular Carcinoma ◽  
Gas Chromatography ◽  
Risk Stratification ◽  
Tricarboxylic Acid Cycle ◽  
Nonnegative Matrix ◽  
Metabolic Reprogramming ◽  
Gas Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry ◽  
Tumor Tissues

Hepatocellular carcinoma (HCC) displays a high degree of metabolic and phenotypic heterogeneity and has dismal prognosis in most patients. Here, a gas chromatography–mass spectrometry (GC-MS)-based nontargeted metabolomics method was applied to analyze the metabolic profiling of 130 pairs of hepatocellular tumor tissues and matched adjacent noncancerous tissues from HCC patients. A total of 81 differential metabolites were identified by paired nonparametric test with false discovery rate correction to compare tumor tissues with adjacent noncancerous tissues. Results demonstrated that the metabolic reprogramming of HCC was mainly characterized by highly active glycolysis, enhanced fatty acid metabolism and inhibited tricarboxylic acid cycle, which satisfied the energy and biomass demands for tumor initiation and progression, meanwhile reducing apoptosis by counteracting oxidative stress. Risk stratification was performed based on the differential metabolites between tumor and adjacent noncancerous tissues by using nonnegative matrix factorization clustering. Three metabolic clusters displaying different characteristics were identified, and the cluster with higher levels of free fatty acids (FFAs) in tumors showed a worse prognosis. Finally, a metabolite classifier composed of six FFAs was further verified in a dependent sample set to have potential to define the patients with poor prognosis. Together, our results offered insights into the molecular pathological characteristics of HCC.

scholarly journals Compartmentation of acetyl CoA studied by analysis of tricarboxylic acid cycle acids and 3-hydroxybutyrate in bile of rats given [2,2,2-2H3]ethanol

1990 ◽  
Vol 265 (2) ◽  
pp. 569-574 ◽  
Author(s):  
C Norsten ◽  
T Cronholm
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Ketone Bodies ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Gas Chromatography Mass Spectrometry ◽  
Acetyl Coa ◽  
Acid Cycle ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Rat Bile

Acetate, 3-hydroxybutyrate, pyruvate, lactate, citrate, 2-oxoglutarate, succinate, fumarate and malate were analysed in rat bile by gas chromatography and gas chromatography/mass spectrometry of their O-melthyloxime-t-butyldimethylsilyl derivatives. The concentration of acetate increased to about 1.8 mmol/l after administration of [2,2,2-2H3]ethanol. Acetate was formed from ethanol to an extent of about 82% and retained all of the 2H at C-2, whereas 15% of the 2H had been lost in the tricarboxylic acid cycle intermediates and 24% in 3-hydroxybutyrate. Thus the exchange of 2H for 1H takes place after formation of acetyl CoA. For citrate and 3-hydroxybutyrate, 41% and 11% respectively was formed from [2,2,2-2H3]ethanol. These results indicate that different pools of acetyl CoA are used for the synthesis of ketone bodies and citrate, with the latter being derived from ethanol to a much larger extent. Smaller fractions of 2-oxoglutarate (16%) and succinate (5%) were derived from [2,2,2--2H3]ethanol, indicating significant contributions from amino acids.

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