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[en] The drive to understand how altered cellular metabolism and cancer are linked has caused a paradigm shift in the focus of cancer research. The discovery of a mutated metabolic enzyme, isocitrate dehydrogenase 1, that leads to accumulation of the oncometabolite 2-hydroxyglutarate, provided significant direct evidence that dysfunctional metabolism plays an important role in oncogenesis. Striking parallels exist with the Krebs cycle enzyme fumarate hydratase (FH), a tumor suppressor, whose mutation is associated with the development of leiomyomata, renal cysts, and tumors. Loss of FH enzymatic activity results in accumulation of intracellular fumarate which has been proposed to act as a competitive inhibitor of 2-oxoglutarate-dependent oxygenases including the hypoxia-inducible factor (HIF) hydroxylases, thus activating oncogenic HIF pathways. Interestingly, our studies have questioned the role of HIF and have highlighted other candidate mechanisms, in particular the non-enzymatic modification of cysteine residues (succination) that could lead to disruption or loss of protein functions, dysfunctional cell metabolism and cell signaling. Here, we discuss the evidence for proposing fumarate as an onco-metabolite.
[en] The invention relates to the determination of 1 α, 25-dihydroxycholecalciferol and of optical enantiomers and racemates thereof. More particularly, the invention is concerned with a radioimmunoassay and a reagent for the determination of 1 α, 25-dihydroxycholecalciferol and of optical enantiomers and racemates thereof, with novel antigens and antibodies useful in the said process and with a process for the preparation of the said antigens and antibodies. The invention is also concerned with novel haptens useful in the preparation of said antigens and with a process for the preparation of said haptens. (author)
[en] Syntheses of modified steroids annulated at the 16-, 17-positions with five- and six-membered heterocycles are reviewed. The biological activity profiles of these compounds as important secondary metabolites are described.
[en] A survey is given of radiopharmaceuticals which have been developed for in vivo nuclear medical procedures in the study of cardiac diseases. Reagents for imaging the cardiac and myocardial blood-pool are discussed. The use of labelled fatty acids and glucose derivatives to visualize the myocardium and detect metabolic defects are described. Scintigraphic techniques for myocardial infarction are mentioned. (Auth.)
[en] Four compounds show a same TLC behavior (Rf 0.67 on Si 60F254 in elution condition of CH2Cl2-MeOH (=10:1, v/v)) and could be isolated into each component only with HPLC (Fig. 2). The structures of four compounds were determined based on spectroscopic analysis (UV, 1H-, 13C-, DEPT, 1H-1H COSY, HMQC, HMBC, and FAB-MS). FAB-mass spectra of four compounds exhibit the same molecular ion peak, i. e. [M+Na]+, and its mass value (m/z) is found 563.1. In the UV spectra, the compound 1 and 2 show the characteristic UV absorption maxima of a conjugated tetraene at 288, 301, 315 nm, and the compound 3 and 4 show those of a conjugated triene at 263, 279, 287 nm (Fig. 2). These observation and spectroscopic data would strongly suggest that these compounds are most likely to be of isomeric relationship
[en] The metabolites of mefenamic acid, a non-steroidal anti-inflammatory drug, were studied in urine of human male and female volunteers. Urine samples were collected at pre-determined time intervals. The concentration of mefenamic acid as free drug was analyzed by spectrophotometry at 285 nm and the metabolites were separated by paper chromatography. The average plus minus SE values of the amount of mefenamic acid in urine of human male and female volunteers were found to be 4.484 plus minus 0.228 micro gram/mL and 4.057 plus minus micro g/mL respectively. The average R/sub f/values of mefenamic acid as free drug in male and female volunteers were found to be 0.76 and 0.77 respectively. And the average R/sub f/ values for the metabolites of mefenamic acid were found to be 0.47 and 0.45 respectively. The method of analysis is accurate, easy, handy and reproducible (author)
[en] Microfungi are a highly diverse group of micro-organisms and important components of the ecosystem with great potential for diverse metabolite production. During a survey of microfungi on leaves in a National Park in Sarawak, an uncommon endophytic microfungus Aspergillus nomius was encountered. The metabolite production of this microfungus was investigated by growing it in a liquid basal medium for 2 weeks. Gas Chromatography - Mass Spectrometry (GC-MS) and Fourier Transform Infrared (FTIR) profiling of the secondary metabolites produced by this microfungus in the liquid medium revealed the presence of 46 different secondary metabolites. The metabolites include saturated hydrocarbons, alkyl halides, alcohols and an unsaturated hydrocarbon. Majority of the metabolites produced were saturated hydrocarbons. Tetracosane, Icosane and 10-Methylicosane were the most abundant metabolites identified while heptadecane and 2,4-dimethylundecane were the least abundant respectively. This study is the first GC-MS and FTIR report of secondary metabolites from A. nomius. The results from this study confirm the ability of microfungi to produce diverse metabolites, including saturated hydrocarbons. (author)
[en] Of several hundred microorganisms randomly selected from the environment, only a fungal isolate identified as Aspergillus niger van Tiegham var. niger was found to transform the phytotoxin thaxtomin A to much less toxic metabolites. The rate and extent of transformation of thaxtomin A was tested under a variety of conditions, including different growth media, biomass concentrations, incubation periods, and shaker speeds. Under optimum conditions the fungus converted thaxtomin A into two major and five minor metabolites. The two major metabolites and three of the five minor metabolites were fully characterized by a combination of mass spectral and nuclear magnetic resonance techniques. When assayed on aseptically produced mini-tubers, the major metabolites proved to be much less phytotoxic than thaxtomin A. (author)
[en] Background: Age- and sex-related changes of metabolites in healthy adult brains have been examined with different 1H magnetic resonance spectroscopy (MRS) methods in varying populations, and with differing results. A long repetition time and short echo time technique reduces quantification errors due to T1 and T2 relaxation effects and makes it possible to measure metabolites with short T2 relaxation times. Purpose: To examine the effect of age on the metabolite concentrations measured by 1H MRS in normal supraventricular white matter using a long repetition time (TR) and a short echo time (TE). Material and Methods: Supraventricular white matter of 57 healthy subjects (25 women, 32 men), aged 13 to 72 years, was examined with a single-voxel MRS at 1.5T using a TR of 6000 ms and a TE of 22 ms. Tissue water was used as a reference in quantification. Results: Myoinositol increased slightly and total N-acetyl aspartate (NAA) decreased slightly with increasing age. Glutamine/glutamate complex (Glx) showed U-shaped age dependence, with highest concentrations in the youngest and oldest subjects. No significant age dependence was found in total choline and total creatine. No gender differences were found. Macromolecule/ lipid (ML) fractions were reliably measurable only in 36/57 or even fewer subjects and showed very large deviations. Conclusion: The concentrations of several metabolites in cerebral supraventricular white matter are age dependent on 1H MRS, even in young and middle-aged people, and age dependency can be nonlinear. Each 1H MRS study of the brain should therefore take age into account, whereas sex does not appear to be so important. The use of macromolecule and lipid evaluations is compromised by less successful quantification and large variations in healthy people