Historical and contemporary stable isotope tracer approaches to studying mammalian protein metabolism
نویسنده
چکیده
Over a century ago, Frederick Soddy provided the first evidence for the existence of isotopes; elements that occupy the same position in the periodic table are essentially chemically identical but differ in mass due to a different number of neutrons within the atomic nucleus. Allied to the discovery of isotopes was the development of some of the first forms of mass spectrometers, driven forward by the Nobel laureates JJ Thomson and FW Aston, enabling the accurate separation, identification, and quantification of the relative abundance of these isotopes. As a result, within a few years, the number of known isotopes both stable and radioactive had greatly increased and there are now over 300 stable or radioisotopes presently known. Unknown at the time, however, was the potential utility of these isotopes within biological disciplines, it was soon discovered that these stable isotopes, particularly those of carbon (13 C), nitrogen (15 N), oxygen (18 O), and hydrogen (2 H) could be chemically introduced into organic compounds, such as fatty acids, amino acids, and sugars, and used to "trace" the metabolic fate of these compounds within biological systems. From this important breakthrough, the age of the isotope tracer was born. Over the following 80 yrs, stable isotopes would become a vital tool in not only the biological sciences, but also areas as diverse as forensics, geology, and art. This progress has been almost exclusively driven through the development of new and innovative mass spectrometry equipment from IRMS to GC-MS to LC-MS, which has allowed for the accurate quantitation of isotopic abundance within samples of complex matrices. This historical review details the development of stable isotope tracers as metabolic tools, with particular reference to their use in monitoring protein metabolism, highlighting the unique array of tools that are now available for the investigation of protein metabolism in vivo at a whole body down to a single protein level. Importantly, it will detail how this development has been closely aligned to the technological development within the area of mass spectrometry. Without the dedicated development provided by these mass spectrometrists over the past century, the use of stable isotope tracers within the field of protein metabolism would not be as widely applied as it is today, this relationship will no doubt continue to flourish in the future and stable isotope tracers will maintain their importance as a tool within the biological sciences for many years to come. © 2016 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc. Mass Spec Rev.
منابع مشابه
Measuring synthesis rates of nitrogen-containing polymers by using stable isotope tracers.
The major N-containing polymer compounds in the body include protein, RNA, and DNA. The endogenous gastrointestinal secretions as well as the portal-drained visceral and peripheral immune responses are basic physiological functions. Elevated endogenous secretions and immune activities, as affected by developmental stages, diets, and management factors, decrease the availability of dietary nutri...
متن کاملLabeling of Human Serum Albumin with Stable Isotope of Bromine; an in Vitro Study
Background: Possibility to trace-label albumin with isotopes results in information concerning its synthesis, breakdown, and distribution in the intra and extra cellular spaces. The iodination of albumin is a widespread procedure used in scientific studies. Bromine not only is more reactive and less expensive than iodine, but bonds more easily with many elements. Therefore, it could be a suitab...
متن کاملStable Isotope Labeling of Mammals (SILAM).
INTRODUCTIONA general approach in quantitative mass spectrometry is to mix a protein sample containing only natural-abundance isotopes with an identical protein sample containing proteins labeled with heavy stable isotopes (e.g., (2)H, (13)C, (15)N, or (18)O). Introduction of stable isotope labels into proteins alters their molecular weight and such changes can be observed on the mass spectrome...
متن کاملRegulation of mammalian nucleotide metabolism and biosynthesis
Nucleotides are required for a wide variety of biological processes and are constantly synthesized de novo in all cells. When cells proliferate, increased nucleotide synthesis is necessary for DNA replication and for RNA production to support protein synthesis at different stages of the cell cycle, during which these events are regulated at multiple levels. Therefore the synthesis of the precur...
متن کاملThe use of stable and radioactive sterol tracers as a tool to investigate cholesterol degradation to bile acids in humans in vivo.
Alterations of cholesterol homeostasis represent important risk factors for atherosclerosis and cardiovascular disease. Different clinical-experimental approaches have been devised to study the metabolism of cholesterol and particularly the synthesis of bile acids, its main catabolic products. Most evidence in humans has derived from studies utilizing the administration of labeled sterols; thes...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 37 شماره
صفحات -
تاریخ انتشار 2018