scholarly journals 1H-NMR Spectroscopy of Body Fluids: Inborn Errors of Purine and Pyrimidine Metabolism

1999 ◽  
Vol 45 (4) ◽  
pp. 539-548 ◽  
Author(s):  
Ron A Wevers ◽  
Udo FH Engelke ◽  
Sytske H Moolenaar ◽  
Christa Bräutigam ◽  
Jan GN de Jong ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Spectral Characteristics ◽  
Sample Volume ◽  
Body Fluids ◽  
Operating Conditions ◽  
Urine Samples ◽  
Pyrimidine Metabolism ◽  
Inborn Errors

Abstract Background: The diagnosis of inborn errors of purine and pyrimidine metabolism is often difficult. We examined the potential of 1H-NMR as a tool in evaluation of patients with these disorders. Methods: We performed 1H-NMR spectroscopy on 500 and 600 MHz instruments with a standardized sample volume of 500 μL. We studied body fluids from 25 patients with nine inborn errors of purine and pyrimidine metabolism. Results: Characteristic abnormalities could be demonstrated in the 1H-NMR spectra of urine samples of all patients with diseases in the pyrimidine metabolism. In most urine samples from patients with defects in the purine metabolism, the 1H-NMR spectrum pointed to the specific diagnosis in a straightforward manner. The only exception was a urine from a case of adenine phosphoribosyl transferase deficiency in which the accumulating metabolite, 2,8-dihydroxyadenine, was not seen under the operating conditions used. Similarly, uric acid was not measured. We provide the 1H-NMR spectral characteristics of many intermediates in purine and pyrimidine metabolism that may be relevant for future studies in this field. Conclusion: The overview of metabolism that is provided by 1H-NMR spectroscopy makes the technique a valuable screening tool in the detection of inborn errors of purine and pyrimidine metabolism.

scholarly journals 1H NMR spectroscopy of body fluids in patients with inborn errors of purine and pyrimidine metabolism

1997 ◽  
Vol 20 (3) ◽  
pp. 345-350 ◽  
Author(s):  
R. A. Wevers ◽  
U. Engelke ◽  
J. J. Rotteveel ◽  
A. Heerschap ◽  
J. G. N. de Jong ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Body Fluids ◽  
Pyrimidine Metabolism ◽  
Inborn Errors

High-resolution 1H-NMR spectroscopy of blood plasma for metabolic studies

1994 ◽  
Vol 40 (7) ◽  
pp. 1245-1250 ◽  
Author(s):  
R A Wevers ◽  
U Engelke ◽  
A Heerschap
Keyword(s):  
Nmr Spectroscopy ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Spin Echo ◽  
Single Pulse ◽  
Plasma Samples ◽  
Inborn Errors ◽  
Glutathione Biosynthesis ◽  
Health And Disease ◽  
Quantitative Analyses

Abstract Although spin-echo techniques are often used to obtain 1H-NMR spectra of serum or plasma samples, they do not provide reliable quantitative analyses of metabolites. We present a standardized procedure, optimized for sensitivity, for using single-pulse 1H-NMR spectroscopy to analyze deproteinized plasma. The detection limit for various metabolites ranges between 2 and 40 mumol/L. The method allows quantitative analysis of many compounds of interest in studies of inborn errors of metabolism, including betaine and dimethylglycine, which cannot be measured easily with other techniques. For lactate, tyrosine, threonine, and alanine, we obtained results that correlated well with those obtained by established techniques. We also present a library containing resonance positions of 38 compounds occurring in plasma samples in health and disease, including 14 as-yet-unidentified resonances. As an example of the diagnostic power of the technique we show a spectrum of a plasma sample from a patient with 5-oxoprolinuria (pyroglutamic aciduria; McKusick 266130), an enzymatic defect in glutathione biosynthesis.

Metabolomic studies of experimental diabetic urine samples by 1H NMR spectroscopy and LC/MS method

2009 ◽  
Vol 97 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Andris Jankevics ◽  
Edvards Liepinsh ◽  
Edgars Liepinsh ◽  
Reinis Vilskersts ◽  
Solveiga Grinberga ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Urine Samples

scholarly journals Synthesis and properties of 1-aminocarbonylmethyl-5-aryl- 4-aroyl-3-hydroxy-3-pyrroline-2-ones

2020 ◽  
Vol 64 (10) ◽  
pp. 28-32
Author(s):  
Vladimir L. Gein ◽  
◽  
Evgenia V. Pastukhova ◽  
Keyword(s):  
Acetic Acid ◽  
Nmr Spectroscopy ◽  
Physicochemical Properties ◽  
Hydrazine Hydrate ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Glacial Acetic Acid ◽  
Spectral Characteristics ◽  
Biologically Active ◽  
Three Component Reaction

3-Hydroxy-3-pyrrolin-2-ones are fully hydrogenated heterocyclic compounds, the base of which is included in a number of biologically active substances and drugs. Scientists' interest in 3-Hydroxy-3-pyrrolin-2-ones is due to the fact that, with their availability and high stability, they also have high reactivity due to the active carbonyl group in the third position of the heterocycle and easily interact with moconucleophiles. In addition, the presence of acyl and ethoxycarbonyl groups in the fourth position of the heterocycle makes it possible to obtain various condensed systems in reactions with binucleophiles, thereby making it possible to expand the range of the indicated compounds. We set the task to prepare 5-aryl-4-acyl-3-hydroxy-3-pyrrolin-2-ones containing an amino-carbonylmethyl substituent in the first position of the heterocycle, which were not previously described in the literature. It was also supposed to establish how the obtained compounds react with hydrazine hydrate. A series of 1-aminocarbonylmethyl-5-aryl-4-aroyl-3-hydroxy-3-pyrrolin-2-ones was obtained by setting up a three-component reaction of aroylpyruvic acid methyl ester with aromatic aldehydes and glycinamide hydrochloride in glacial acetic acid. The structure of the obtained compounds was established on the basis of IR and 1H NMR spectroscopy data. Based on the data of 1H NMR spectroscopy and a positive reaction with an alcoholic solution of iron(III) chloride, the predominant existence of the obtained compounds in the enol form was established. The article describes the mechanism of three-component reactions, the structural formulas of the obtained compounds, their physicochemical properties and spectral characteristics, as well as the yields of the reaction products. We have also studied the interaction of 1-substituted 5-aryl-4-acyl-3-hydroxy-3-pyrrolin- 2-ones with such a binucleophilic reagent as hydrazine hydrate. As a result of refluxing 1-amino-carbonylmethyl-3-hydroxy-4-(4-methoxybenzoyl)-5-(2-chlorophenyl)-3-pyrrolin-2-one and hydrazine hydrate in glacial acetic acid, 2-[4-(2-chlorophenyl)-3-(4-methoxyphenyl)-6-oxo-4,6-dihydropyrrolo [3,4-c] pyrazol-5(1H)-yl] acetamide. The article describes the proposed reaction mechanism, product yield, its physicochemical properties and spectral characteristics.

scholarly journals Synthesis of 5-aryl-4-acyl-3-hydroxy- 1-carboxymethyl-3-pyrrolin-2-ones

2020 ◽  
Vol 64 (11) ◽  
pp. 9-12
Author(s):  
Vladimir L. Gein ◽  
◽  
Evgenia V. Pastukhova ◽  
Keyword(s):  
Nmr Spectroscopy ◽  
Carbonyl Group ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Spectral Characteristics ◽  
Alcoholic Solution ◽  
Biologically Active ◽  
Acyl Residue ◽  
Reaction Products ◽  
Three Component Reaction

5-Aryl-1,4-disubstituted terahydropyrrole-2,3-diones are five-membered nitrogen heterocycles containing in the first alkyl position or an aryl functionalized substituent and in the fourth position in another state of nature an acyl residue. Trahydropyrrole-2,3-diones constitute a significant class of available and stable substances. Along with this, they easily enter into reactions with various nucleophilic reagents due to the highly reactive carbonyl group in the third position of the heterocycle. The presence of the latter, as well as the carbonyl group of the side chain, makes it possible to form various condensed systems from heterocycles in reactions with binucleophilic reagents. The synthesis of biologically active substances based on 1,4,5-trisubstituted tetrahydropyrrole-2,3-diones is one of the promising ways of using this class of compounds. Previously, it was found that 1,4,5-trisubstituted 3-hydroxy-3-pyrin-2-ones have anti-inflammatory, analgesic, antimicrobial, nootropic, antiplatelet and antiviral activity. We set the task to obtain 5-aryl-4-acyl-3-hydroxy-3-pyrrolin-2-ones, in the first position of the heterocycle there is a carboxymethyl substituent. By setting up a three-component reaction of acylpyruvic acid ether with aromatic aldehydes and glycine in dioxane in dioxane. The structure of the compound was established on the basis of IR and 1H NMR spectroscopy data. Based on the data of 1H NMR spectroscopy and a positive reaction with an alcoholic solution of iron(III) chloride, the predominant presence of compounds in the enol form was established. The article presents the proposed mechanism and schemes of the formula for the synthesis of 5-aryl-4-acyl-3-hydroxy-1-carboxymethyl-3-pyrrolin-2-ones, their physicochemical and spectral characteristics, as well as the yields of the reaction products.

scholarly journals A fast 1H NMR spectroscopy procedure for quantitative determination of N-acetylaspartate in urine samples

2009 ◽  
Vol 404 (2) ◽  
pp. 166-168 ◽  
Author(s):  
Gláucia M.S. Pinheiro ◽  
Ernani A. Basso ◽  
Barbara C. Fiorin ◽  
F. Cendes ◽  
Roberto Rittner ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Quantitative Determination ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Urine Samples

Quality assurance in the pre-analytical phase of human urine samples by 1H NMR spectroscopy

2016 ◽  
Vol 589 ◽  
pp. 10-17 ◽  
Author(s):  
Kathrin Budde ◽  
Ömer-Necmi Gök ◽  
Maik Pietzner ◽  
Christine Meisinger ◽  
Michael Leitzmann ◽  
...  
Keyword(s):  
Quality Assurance ◽  
Nmr Spectroscopy ◽  
1H Nmr ◽  
Human Urine ◽  
1H Nmr Spectroscopy ◽  
Urine Samples ◽  
Human Urine Samples ◽  
Analytical Phase

scholarly journals Diagnosing Inborn Errors of Lipid Metabolism with Proton Nuclear Magnetic Resonance Spectroscopy

2006 ◽  
Vol 52 (7) ◽  
pp. 1395-1405 ◽  
Author(s):  
Marlies Oostendorp ◽  
Udo FH Engelke ◽  
Michèl AAP Willemsen ◽  
Ron A Wevers
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Lipid Metabolism ◽  
Nmr Spectroscopy ◽  
Magnetic Resonance ◽  
Blood Plasma ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Correct Diagnosis ◽  
Proton Nuclear Magnetic Resonance ◽  
Inborn Errors

Abstract Background: Many severe diseases are caused by defects in lipid metabolism. As a result, patients often accumulate unusual lipids in their blood and tissues, and proper identification of these lipids is essential for correct diagnosis. In this study, we investigated the potential use of proton nuclear magnetic resonance (1H-NMR) spectroscopy to simultaneously identify and quantify (un)usual lipids present in the blood of patients with different inborn errors of lipid metabolism. Methods: We extracted blood plasma or serum lipids in chloroform–methanol (2:1 by volume). After addition of the nonvolatile chemical shift and concentration reference compound octamethylcyclotetrasiloxane, we performed 1H-NMR measurements on a 500-MHz spectrometer. Assignments were based on the literature, computer simulations, and reference spectra of relevant authentic standards. Results: Spectra of normal plasma samples allowed the identification of 9 lipid species. We found good correlation between conventional methods and 1H-NMR for cholesterol and triglyceride concentrations. We also investigated 4 inborn errors of lipid metabolism (3 in sterol metabolism and 1 in fatty acid metabolism). NMR analysis led to a correct diagnosis for all 4 diseases, whereas the concentration of the diagnostic metabolite could be determined for 3. Conclusions: 1H-NMR spectroscopy of blood plasma or serum lipid extracts can be used to accurately identify and quantify lipids. The method can also identify unusual lipids in the blood of patients with inborn errors of lipid metabolism. This technique may therefore be applicable in clinical diagnosis and follow-up.

scholarly journals N-Acetylated Metabolites in Urine: Proton Nuclear Magnetic Resonance Spectroscopic Study on Patients with Inborn Errors of Metabolism

2004 ◽  
Vol 50 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Udo F H Engelke ◽  
Maria L F Liebrand-van Sambeek ◽  
Jan G N de Jong ◽  
Jules G Leroy ◽  
Éva Morava ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Nmr Spectroscopy ◽  
Magnetic Resonance ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Inborn Errors Of Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Two Dimensional ◽  
Inborn Errors ◽  
Acetylated Metabolites

Abstract Background: There is no comprehensive analytical technique to analyze N-acetylated metabolites in urine. Many of these compounds are involved in inborn errors of metabolism. In the present study, we examined the potential of proton nuclear magnetic resonance (1H-NMR) spectroscopy as a tool to identify and quantify N-acetylated metabolites in urine of patients with various inborn errors of metabolism. Methods: We performed 1H-NMR spectroscopy on a 500 MHz spectrometer. Using a combination of one- and two-dimensional correlation spectroscopy (COSY) 1H-NMR spectra, we were able to assign and quantify resonances of characteristic N-acetylated compounds products in urine of patients with 13 inborn errors of metabolism. Results: The disease-specific N-acetylated metabolites were excreted at concentrations >100 μmol/mmol of creatinine in the patients’ urine. In control urine samples, the concentration of individual N-acetyl-containing compounds was <40 μmol/mmol of creatinine. The combination of one- and two-dimensional COSY NMR spectroscopy led to the correct diagnosis of nine different inborn errors of metabolism. No abnormalities were observed in the spectra of urine from patients with GM1- or GM2-gangliosidosis. We also determined the 1H-NMR characteristics of N-acetylated metabolites that may be relevant to human metabolism. Conclusion: 1H-NMR spectroscopy may be used to identify and quantify N-acetylated metabolites of diagnostic importance for the field of inborn errors of metabolism.

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