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      A Specific Urinary Amino Acid Profile Characterizes People with Kidney Stones

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          Abstract

          Background

          Urolithiasis is the process of stone formation in the urinary tract. Its etiology is only partly known, and efficient therapeutic approaches are currently lacking. Metabolomics is increasingly used in biomarkers discovery for its ability to identify mediators of relevant (patho)physiological processes. Amino acids may be involved in kidney stone formation. The aim of the present study was to investigate the presence of an amino acid signature in stone former urine through a targeted metabolomic approach.

          Methods

          A panel of 35 amino acids and derivatives was assessed in urines from 15 stone former patients and 12 healthy subjects by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to define amino acid profiles of cases and controls. Results and Discussion. Our approach led to the definition of a specific amino acid fingerprint in people with kidney stones. A urinary amino acid profile of stone formers was characterized by lower levels of α-aminobutyric acid, asparagine, ethanolamine, isoleucine, methionine, phenylalanine, serine, tryptophan, and valine. Metabolomic analysis may lend insights into the pathophysiology of urolithiasis and allow tracking this prevalent condition over time.

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          Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption.

          Tomoyoshi Soga, Richard Baran, Makoto Suematsu … (2006)
          Metabolomics is an emerging tool that can be used to gain insights into cellular and physiological responses. Here we present a metabolome differential display method based on capillary electrophoresis time-of-flight mass spectrometry to profile liver metabolites following acetaminophen-induced hepatotoxicity. We globally detected 1,859 peaks in mouse liver extracts and highlighted multiple changes in metabolite levels, including an activation of the ophthalmate biosynthesis pathway. We confirmed that ophthalmate was synthesized from 2-aminobutyrate through consecutive reactions with gamma-glutamylcysteine and glutathione synthetase. Changes in ophthalmate level in mouse serum and liver extracts were closely correlated and ophthalmate levels increased significantly in conjunction with glutathione consumption. Overall, our results provide a broad picture of hepatic metabolite changes following acetaminophen treatment. In addition, we specifically found that serum ophthalmate is a sensitive indicator of hepatic GSH depletion, and may be a new biomarker for oxidative stress. Our method can thus pinpoint specific metabolite changes and provide insights into the perturbation of metabolic pathways on a large scale and serve as a powerful new tool for discovering low molecular weight biomarkers.
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            The growing role of precision and personalized medicine for cancer treatment

            Paulina Krzyszczyk, Alison Acevedo, Erika J. Davidoff … (2018)
            Cancer is a devastating disease that takes the lives of hundreds of thousands of people every year. Due to disease heterogeneity, standard treatments, such as chemotherapy or radiation, are effective in only a subset of the patient population. Tumors can have different underlying genetic causes and may express different proteins in one patient versus another. This inherent variability of cancer lends itself to the growing field of precision and personalized medicine (PPM). There are many ongoing efforts to acquire PPM data in order to characterize molecular differences between tumors. Some PPM products are already available to link these differences to an effective drug. It is clear that PPM cancer treatments can result in immense patient benefits, and companies and regulatory agencies have begun to recognize this. However, broader changes to the healthcare and insurance systems must be addressed if PPM is to become part of standard cancer care.
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              Plasma concentrations and intakes of amino acids in male meat-eaters, fish-eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort

              J Schmidt, S. Rinaldi, A Scalbert … (2015)
              Background/Objectives: We aimed to investigate the differences in plasma concentrations and in intakes of amino acids between male meat-eaters, fish-eaters, vegetarians and vegans in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. Subjects/Methods: This cross-sectional analysis included 392 men, aged 30–49 years. Plasma amino acid concentrations were measured with a targeted metabolomic approach using mass spectrometry, and dietary intake was assessed using a food frequency questionnaire. Differences between diet groups in mean plasma concentrations and intakes of amino acids were examined using analysis of variance, controlling for potential confounding factors and multiple testing. Results: In plasma, concentrations of 6 out of 21 amino acids varied significantly by diet group, with differences of −13% to +16% between meat-eaters and vegans. Concentrations of methionine, tryptophan and tyrosine were highest in fish-eaters and vegetarians, followed by meat-eaters, and lowest in vegans. A broadly similar pattern was seen for lysine, whereas alanine concentration was highest in fish-eaters and lowest in meat-eaters. For glycine, vegans had the highest concentration and meat-eaters the lowest. Intakes of all 18 dietary amino acids differed by diet group; for the majority of these, intake was highest in meat-eaters followed by fish-eaters, then vegetarians and lowest in vegans (up to 47% lower than in meat-eaters). Conclusions: Men belonging to different habitual diet groups have significantly different plasma concentrations of lysine, methionine, tryptophan, alanine, glycine and tyrosine. However, the differences in plasma concentrations were less marked than and did not necessarily mirror those seen for amino acid intakes.
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                Author and article information

                Contributors
                Pietro Manuel Ferraro:
                ORCID: https://orcid.org/0000-0002-1379-022X
                Journal
                Journal ID (nlm-ta): Dis Markers
                Journal ID (iso-abbrev): Dis. Markers
                Journal ID (publisher-id): DM
                Title: Disease Markers
                Publisher: Hindawi
                ISSN (Print): 0278-0240
                ISSN (Electronic): 1875-8630
                Publication date Collection: 2020
                Publication date (Electronic): 30 June 2020
                Volume: 2020
                Electronic Location Identifier: 8848225
                Affiliations
                1Università Cattolica del Sacro Cuore, Rome, Italy
                2Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy
                3Department of Physical and Chemical Sciences, Università degli Studi dell'Aquila, L'Aquila, Italy
                4Department of Chemistry, Sapienza Università di Roma, Rome, Italy
                Author notes

                Academic Editor: Robert Pichler

                Author information
                https://orcid.org/0000-0002-1379-022X
                Article
                DOI: 10.1155/2020/8848225
                PMC ID: 7345965
                SO-VID: f93d2d3e-cb54-4439-9661-682db82e8655
                Copyright © Copyright © 2020 Aniello Primiano et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 10 April 2020
                Date revision received : 8 June 2020
                Date accepted : 15 June 2020
                Categories
                Subject: Research Article

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