Isotope Labeling Ratios: A Tool for the Exploration of Metabolic Compartments

  • Joanne K. Kelleher
  • Robert T. Mallet
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 194)


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.


Metabolite Pool Label Metabolite Enzyme Aggregate Endogenous Pool Mitochondrial Pyruvate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Blum, J.J. 1978. Influence of metabolic compartmentation on the quantitative analysis of intermediary metabolism, in: dMicroenvironments and Metabolic Compartmentation,d R. Estabrook and P. Srere, ed., Academic, New York.Google Scholar
  2. Exton, J.H, and C.R. Park. 1967. Control of gluconeogenesis in liver: I. General features of gluconeogenesis in the perfused livers of rats. J. Biol. Chem., 242: 2622.PubMedGoogle Scholar
  3. Heath, D.F. 1968. Redistribution of carbon label by reactions involved in glycolysis, gluconeogensis, and the tricarboxylic acid cycle in rat liver. Biochem. J., 110: 313.PubMedGoogle Scholar
  4. Hetenyi, G., Jr. 1982. Correction for the metabolic exchange of 14C for 12C atoms in the pathway of gluconeogenesis in vivo, Fed. Proc. 41: 104.PubMedGoogle Scholar
  5. Katz, J. and R. Rognstad. 1978. Compartmentation of glucose metabolism in liver, in: dMicroenvironments and Metabolic Compartmentation, d R. Estabrook and P. Srere, ed., Academic, New York.Google Scholar
  6. Kelleher, J.K. 1984. Analysis of the tricarboxylic acid cycle using citrate 14C specific activity ratios, Am. J. Physiol., (in press).Google Scholar
  7. Mallet, R.T., J.K. Kelleher, and M.J. Jackson. 1984. Substrate metabolism by rat jejunal epithelium: The role of glutamine. Fed. Proc., 43: 446.Google Scholar
  8. Mendes-Mourao, J., A.P. Halestrap, D.M. Crisp, and C.I. Pogson. 1975. The involvement of mitochondrial pyruvate transport in the pathways of gluconeogenesis from serine and alanine in isolated rat and mouse liver cells. FEBS Letters 53: 29PubMedCrossRefGoogle Scholar
  9. Radziuk, J. 1982. Sources of carbon in hepatic glycogen synthesis during absorption of an oral glucose load in humans, Fed. Proc. 41: 110.PubMedGoogle Scholar
  10. Soboll, S.,R. Elbers, and H.W. Heldt. 1979. Metabolite measurements in mitochondria and in the extramitochondrial compartment by fractionation of freeze-stopped liver tissue in nonaqueous media. Methods in Enzymol. 56: 201.CrossRefGoogle Scholar
  11. Zuurendonk, P.F., M.E. Tischler, T.P.M. Akerboom, R. Van Der Meer, J.R. Williamson, and J.M. Tager. 1979. Rapid separation of particulate and soluble fractions from isolated cell preparations (Digitonin and cell cavitation procedures). Methods in Enzymol. 56: 207.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Joanne K. Kelleher
    • 1
  • Robert T. Mallet
    • 1
  1. 1.Department of PhysiologyThe George Washington UniversityUSA

Personalised recommendations