Isotope Labeling Ratios: A Tool for the Exploration of Metabolic Compartments
Reports of metabolic compartmentation often stem from data viewed as unfortunate by the reporters. Namely, an investigation of a metabolic pathway by isotopic tracer techniques yields results incompatible with the starting assumption that a single pool of each metabolite is present in the system. Thus compartmentation is added so that the data are consistent. A reader offered a specific compartmentalized arrangement in the closing paragraphs of a paper may wonder what other possible compartmental arrangements might have been uncovered if, from the onset of the project, multiple compartments of each metabolite had been assumed. Our goal is to describe techniques for determining the information available from steady state isotopic tracer studies if we assume that multiple pools of each metabolite exist which mix when the system is analyzed. Essentially we assume that the specific radioactivity (SA) of metabolite pools cannot be determined by experiment. We are particularly interested in the application of these techniques to investigations of oxidative energy metabolism and pathways involving metabolic cycles. Our previous studies have focused on the TCA cycle (Kelleher, 1984; Mallet et al., 1984). In this area of metabolism, the presence of enzyme aggregates and a variety of compartments including mitochondrial and cytoplasmic spaces render the estimation rates from isotopic tracer studies especially perilous.
KeywordsMetabolite Pool Label Metabolite Enzyme Aggregate Endogenous Pool Mitochondrial Pyruvate
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