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Supplying Muscle Machines with Energy
Published in Peter W. Hochachka, Muscles as Molecular and Metabolic Machines, 2019
Unlike β-oxidation and the ETS, the Krebs cycle reactions are often considered as operating in solution in the mitochondrial matrix. Recently, however, this position has become less clear and certainly controversial. For example, mildly disrupted mitochondria can be prepared, which show exposed if readily sedimentable Krebs cycle enzymes. When either fumarate oxidation or the MDH-CS (malate dehydro-genase-citrate synthase)-coupled enzyme system are analyzed, relative kinetic advantages are observed over fully solubilized enzyme preparations. From these data Srere and his coworkers (Robinson et al., 1987) propose that the Krebs cycle in situ exists as a sequential complex of enzymes, a metabolon, favoring channelling of metabolites along the metabolic pathway and electrons directly to the ETS (as in the case of coupling between MDH and NADH ubiquinone oxidoreductase, Complex I in the ETS). Interestingly, the kinetic advantages observed for these coupled reactions are more sensitive to disruption than are the binding interactions with the overall particle; i.e., enzyme-enzyme interactions favoring metabolite hand-offs along the Krebs cycle are more fragile than are enzyme-inner mitochondrial membrane interactions (Robinson et al., 1987). This is one reason why experimental support for the metabolon concept has been difficult to obtain, and only now is the concept receiving broader attention (not all favorable, we hasten to add!).
Overcoming Chronic and Degenerative Diseases with Energy Medicine 1
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
A much more sensible concept for biochemical reactions is the metabolon, an orderly sequence of enzymes anchored on a structure such as a membrane or cytoskeletal filament (Srere 1985). A substrate molecule interacting with the first enzyme in the sequence is acted on and the reaction product is then quickly passed to the next enzyme, and so on. There is evidence for a Krebs cycle metabolon and for substrate channeling through the metabolon (Wu and Minteer 2014). While there is increasing evidence for this model, it is usually given only a footnote in biochemistry texts, which typically depict virtually all reactions as molecules more or less floating on the page, with no description of how they manage to find each other (examples are shown in Figure 27.7). Several books present organic chemistry more realistically, based on transfers of energetic electrons (Eberson 2011; Balzani 2001; Scudder 2013).
Mass spectrometry-based metabolomics diagnostics – myth or reality?
Published in Expert Review of Proteomics, 2021
Oxana P. Trifonova, Dmitri L. Maslov, Elena E. Balashova, Petr G. Lokhov
For the development of new clinical diagnostics tests, MS-based metabolomics has potential – both as a preliminary discovery base for routine testing, and as a prototype of a multi-test, which we hope will be introduced into clinical practice in the near future. One of the possible ways to develop multi-tests is the FDA regulated type of in vitro diagnostics – laboratory-developed test (LDT). LDTs can be used to measure or detect a wide variety of analytes within a single laboratory where it was designed and manufactured. A number of these tests were developed by Metabolon in 2018 and used in the Clinical Laboratory Improvement Amendments (CLIA) certified laboratories for the diagnosis of metabolic disorders by determining up to 1,000 metabolites in blood plasma and generating a heat map of metabolite Z-scores, which can be used to identify altered metabolic pathways. In addition, the company offers a clinically confirmed Quantose Impaired Glucose Tolerance Test, which uses a proprietary algorithm to produce an ‘IGT score’ based on a combination of glucose and seven metabolites. As LDTs, these tests have not been approved by the FDA but can be used in clinics as auxiliary tests and in combination with other standard clinical diagnostic tests [60]. Thus, MS-based metabolomics diagnostics have the potential to become a reality. However, the development and introduction of protocols for standardizing the research workflow, as well as clear compliance with all procedures, are required.
Diurnal variation of metabolites in three individual participants
Published in Chronobiology International, 2019
Fangyi Gu, Elizabeth B. Klerman, Sungduk Kim, Steve Moore, Kai Yu, Paul S. Albert, Neil E Caporaso
Metabolomics assays were performed by Metabolon Inc.; the platform and process have been described elsewhere (Evans et al. 2009; Suhre et al. 2011). Study samples were transported to Metabolon on dry ice and immediately stored at −80°C. At the time of analysis, samples were extracted and prepared for analysis using Metabolon’s standard solvent extraction method. The extracted samples were analyzed using ultra high-performance liquid-phase chromatography and gas chromatography coupled with mass spectrometry and tandem mass spectrometry. The mass spectra peaks were compared with a chemical reference library generated from over 2500 standards, to identify individual metabolites. The Metabolon Inc. detected 663 metabolites with known identity in plasma; all were included for our analyses.
Gut microbiota composition as a candidate risk factor for dimethyl fumarate-induced lymphopenia in multiple sclerosis
Published in Gut Microbes, 2022
Martin Diebold, Marco Meola, Srinithi Purushothaman, Lena K Siewert, Elisabeth Pössnecker, Tim Roloff, Raija LP Lindberg, Jens Kuhle, Ludwig Kappos, Tobias Derfuss, Adrian Egli, Anne-Katrin Pröbstel
Serum samples from the first 14 patients (available at the time point of analysis) within this cohort were characterized for metabolomics by UPLC-MS/MS, as described in.6 Each sample was analyzed using acidic positive ion conditions, basic negative ion optimized conditions, and negative ionization. Blinded data were processed and normalized by Metabolon Inc. (Durham, USA) for all assessed samples as described previously.6 Results were verified by paired analysis (for time points T1 and T2) for each observation and assessed using RF analysis on all measured metabolites.