title: The why and how of amino acid analytics in cancer diagnostics and therapy.
abstract: Pathological alterations in cell functions are frequently accompanied by metabolic reprogramming including modifications in amino acid metabolism. Amino acid detection is thus integral to the diagnosis of many hereditary metabolic diseases. The development of malignant diseases as metabolic disorders comes along with a complex dysregulation of genetic and epigenetic factors affecting metabolic enzymes. Cancer cells might transiently or permanently become auxotrophic for non-essential or semi-essential amino acids such as asparagine or arginine. Also, transformed cells are often more susceptible to local shortage of essential amino acids such as methionine than normal tissues. This offers new points of attacking unique metabolic features in cancer cells. To better understand these processes, highly sensitive methods for amino acid detection and quantification are required. Our review summarizes the main methodologies for amino acid detection with a particular focus on applications in biomedicine and cancer, provides a historical overview of the methodological pre-requisites in amino acid analytics. We compare classical and modern approaches such as the combination of gas chromatography and liquid chromatography with mass spectrometry (GC-MS/LC-MS). The latter is increasingly applied in clinical routine. We therefore illustrate an LC-MS workflow for analyzing arginine and methionine as well as their precursors and analogs in biological material. Pitfalls during protocol development are discussed, but LC-MS emerges as a reliable and sensitive tool for the detection of amino acids in biological matrices. Quantification is challenging, but of particular interest in cancer research as targeting arginine and methionine turnover in cancer cells represent novel treatment strategies.
authors.affiliation: OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Manig
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Radiopharmaceutical and Chemical Biology, Dresden, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kuhne
authors.affiliation: OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Cläre
authors.initials: C
authors.lastname: von Neubeck
authors.affiliation: Department of Chemistry and Food Chemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schwarzenbolz
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Zhanru
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Kessler
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department Radiopharmaceutical and Chemical Biology, Dresden, Germany; Department of Chemistry and Food Chemistry, Technische Universität Dresden, Dresden, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.affiliation: OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany; CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK. Electronic address: leoni.kunz-schughart@oncoray.de.
authors.forename: Leoni A
authors.initials: LA
authors.lastname: Kunz-Schughart
mesh_terms: D000596:Amino Acids / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid; D004586:Electrophoresis / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*
chemical_list: D000596:Amino Acids; D014408:Biomarkers, Tumor