Identification of New Medium-Chain Acylcarnitines Present in Normal Human Urine

Libert, R.; Vanhoof, F.; Thillaye, M; Vincent, Marie‐Françoise; Nassogne, Marie‐Cécile; Stroobant, Vincent; Hoffmann, Edmond de; Schanck, André

doi:10.1006/abio.1997.2274

Cited by 15 publications

(7 citation statements)

References 16 publications

(7 reference statements)

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“…These researchers further found that the acylcarnitines with a cyclopropane ring in their fatty acid moieties disappeared in the urine of humans treated with antibiotic. Fatty acids with cyclopropane rings can be synthesized in bacterial membranes by cyclopropane fatty acid synthase (27). Therefore, it has been proposed that cis-11,12methylene-pentadecanoic acid generated by cyclopropane fatty acid synthase in bacteria could be absorbed and metabolized through ␤-oxidation in mitochondria to form cis-3,4-methylene-heptanoyl coenzyme A, which would then be converted into acylcarnitines and excreted (28).…”

Section: Resultsmentioning

confidence: 99%

Fecal Microbiota Transplantation in Experimental Ulcerative Colitis Reveals Associated Gut Microbial and Host Metabolic Reprogramming

Yan

Gao

et al. 2018

Appl Environ Microbiol

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Fecal microbiota transplantation (FMT) is gaining attention for the treatment of ulcerative colitis (UC). Data from individual case studies have suggested that FMT may be beneficial for UC, but the detailed microbial and molecular basis remains unknown. Here, we employ 16S rRNA gene sequencing and metabolomics to investigate the influence of FMT on gut microbial community composition and host metabolism in the dextran sulfate sodium-induced UC rat model. The findings from this pilot study suggest that FMT from normal donors to UC recipients could alleviate UC symptoms without close resemblance of donor's gut microbial and metabolic pattern. Meanwhile, FMT from UC donors to normal recipient rats triggered UC symptoms, UC-prone microbial shift, and host metabolic adaption. Gut microbiota under normal conditions could maintain stable species richness and diversity upon FMT intervention, but the disturbed gut microbiota under UC conditions could not maintain such homeostasis. Significant correlations between altered bacterial composition and host metabolism could be assigned to the pathological effects of UC (accounting for 8.0 to 16.2% of total variance) and/or the FMT intervention effects (3.9 to 7.0% of total variance). Overall, our study reveals diverse gut microbial shifts in UC related FMT and their association with host metabolic reprogramming. This study combined clinical symptoms measurement, 16S rRNA gene microbial profiling and metabolomics to comprehensively investigate the gut bacterial and host metabolic association and reprogramming in FMT-treated experimental UC. These data can advance our understanding of the effect of FMT on UC and the involvement of gut microbial dysbiosis in the development of UC.

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Section: Resultsmentioning

confidence: 99%

Fecal Microbiota Transplantation in Experimental Ulcerative Colitis Reveals Associated Gut Microbial and Host Metabolic Reprogramming

Yan

Gao

et al. 2018

Appl Environ Microbiol

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“…New metabolites continue to be discovered even in well-studied diseases (21,22,31 ), and the metabolomics approach permits analysis of an unprecedented range of compounds. In this study, metabolites such as unsaturated acylcarnitines, isovaleryl carnitine, and ␥-butyrobetaine were associated with MMA and PA.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics Identifies Perturbations in Human Disorders of Propionate Metabolism

et al. 2007

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Background: We applied untargeted mass spectrometrybased metabolomics to the diseases methylmalonic acidemia (MMA) and propionic acidemia (PA). Methods: We used a screening platform that used untargeted, mass-based metabolomics of methanolextracted plasma to find significantly different molecular features in human plasma samples from MMA and PA patients and from healthy individuals. Capillary reverse phase liquid chromatography (4 L/min) was interfaced to a TOF mass spectrometer, and data were processed using nonlinear alignment software (XCMS) and an online database (METLIN) to find and identify metabolites differentially regulated in disease. Results: Of the approximately 3500 features measured, propionyl carnitine was easily identified as the best biomarker of disease (P value 1.3 ؋ 10 ؊18 ), demonstrating the proof-of-concept use of untargeted metabolomics in clinical chemistry discovery. Five additional acylcarnitine metabolites showed significant differentiation between plasma from patients and healthy individuals, and ␥-butyrobetaine was highly increased in a subset of patients. Two acylcarnitine metabolites and numerous unidentified species differentiate MMA and PA. Many metabolites that do not appear in any public database, and that remain unidentified, varied significantly between normal, MMA, and PA, underscoring the complex downstream metabolic effects resulting from the defect in a single enzyme. Conclusions: This proof-of-concept study demonstrates that metabolomics can expand the range of metabolites

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“…Determination of acylcarnitines is challenging and has been addressed using a variety of chromatographic, derivatization, or detection schemes including radioisotopic exchange/HPLC, HPLC/UV, HPLC/fluorescence, GC/MS, CE, CE/MS, and HPLC/tandem MS . However, today the most common method used to analyze acylcarnitines begins with the esterification of acylcarnitines by means of high-temperature acylation followed by detection using tandem MS. , Primarily due to its simplicity and rapidity, this approach has been applied with much success to programs for newborn screening and contributed greatly to our understanding of the role of acylcarnitines in metabolic disorders.…”

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confidence: 99%

Strategy for the Isolation, Derivatization, Chromatographic Separation, and Detection of Carnitine and Acylcarnitines

2005

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A strategy for detection of carnitine and acylcarnitines is introduced. This versatile system has four components: (1) isolation by protein precipitation/desalting and cation-exchange solid-phase extraction, (2) derivatization of carnitine and acylcarnitines with pentafluorophenacyl trifluoromethanesulfonate, (3) sequential ion-exchange/reversed-phase chromatography using a single non-end-capped C8 column, and (4) detection of carnitine and acylcarnitine pentafluorophenacyl esters using an ion trap mass spectrometer. Recovery of carnitine and acylcarnitines from the isolation procedure is 77-85%. Derivatization is rapid and complete with no evidence of acylcarnitine hydrolysis. Sequential ion-exchange/reversed-phase HPLC results in separation of reagent byproducts from derivatized carnitine and acylcarnitines, followed by reversed-phase separation of carnitine and acylcarnitine pentafluorophenacyl esters. Detection by MS/MS is highly selective, with carnitine pentafluorophenacyl ester yielding a strong product ion at m/z 311 and acylcarnitine pentafluorophenacyl ester fragmentation yielding two product ions: (1) loss of m/z 59 and (2) generation of an ion at m/z 293. To demonstrate this analytical strategy, phosphate buffered serum albumin was spiked with carnitine and 15 acylcarnitines and analyzed using the described protein precipitation/desalting and cation-exchange solid-phase extraction isolation, derivatization with pentafluorophenacyl trifluoromethanesulfonate, chromatography using the sequential ion-exchange/reversed-phase chromatography HPLC system, and detection by MS and MS/MS. Successful application of this strategy to the quantification of carnitine and acetylcarnitine in rat liver is shown.

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Identification of New Medium-Chain Acylcarnitines Present in Normal Human Urine

Cited by 15 publications

References 16 publications

Fecal Microbiota Transplantation in Experimental Ulcerative Colitis Reveals Associated Gut Microbial and Host Metabolic Reprogramming

Fecal Microbiota Transplantation in Experimental Ulcerative Colitis Reveals Associated Gut Microbial and Host Metabolic Reprogramming

Metabolomics Identifies Perturbations in Human Disorders of Propionate Metabolism

Strategy for the Isolation, Derivatization, Chromatographic Separation, and Detection of Carnitine and Acylcarnitines

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