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.

Diagnostic value of plasma tryptophan and symmetric dimethylarginine levels for acute kidney injury among tacrolimus-treated kidney transplant patients by targeted metabolomics analysis

“…Once renal dysfunction occurs, both the lost control of AA metabolism by kidney as well as the impact of renal failure and acidosis on whole-body nitrogen metabolism would contribute to the disturbed plasma AA levels 8 . Data from previous researches had shown promising evidence of AA analytics in monitoring the progress of kidney diseases 9 . AA profile in patients’ plasma and urine were of relevance with their clinical evaluation not only in different stages of chronic kidney disease 10 , but also in the AKIs 11 , 12 .…”

A cost-effective approach to produce 15N-labelled amino acids employing Chlamydomonas reinhardtii CC503

“…[ 1 ]. Therefore, the determination of amino acids in biological samples is important not only in the food industry or drug development but also in laboratory medicine as abnormal levels of these compounds are associated with diseases or metabolic disorders [ 2 ].…”

Pre-clinical study of subchronic toxicity of ormustine on rats

“…В числе синтезированных и прошедших отбор соединений оказалось производное из класса НАМ на основе L-орнитина, получившее название Ормустин и прошедшее далее ряд доклинических испытаний в ФГБУ «НМИЦ онкологии им. Н. Н. Блохина» Минздрава России [2,[4][5][6].…”