On the Calculation of "Turnover Time" and "Turnover Rate" From Experiments Involving the Use of Labeling Agents

Abstract

Although labeling agents have been widely used to characterize the course of reactions in the animal body, their application to quantitative aspects of the turnover of a substance has been slow to develop.I r a certain fraction of the administered isotopic substance a is incorporated into a compound, at least the same fraction of the total administered labeled substancO must have been converted into that compound. Such a calculation gives a minimum value for the conversion of a labeled substance into a compound. Fishier (1) showed that the fraction of the administered pn recovered in the phospholipid of liver, muscle, or blood of rats after a 12 hour interval was the same even though the amounts of labeled phosphate injected varied from 6 to 48 rag. This demonstrates that the administered labeled phosphate was negligible in comparison with the phosphate available for incorporation into phospholipids in the animal body. It must therefore be obvious that such minimum values have little significance, for when the amount of injected labded substance was ~aried eightfold the minimum value was altered to the same extent.For the above type of calculation to yield a correct measure of the amount of labeled atoms ~ incorporated into a substance, the amount of labeled molecules injected should be large enough to render negligible the amount of those molecules already present in the organism. Such a procedure, however--namely one in which the amount of injected substance is large enough to yield a correct measure of the amount of newly formed compound--would probably disturb the normal metabolism of the organism.Artom et al. made an interesting contribution to this field, well realizing the difficulties involved in simplifying the complex system in which most of the biological reactions occur (2).By means of repeated injections of Pn Heresy and Hahn (3) maintained a constant specific activity of inorganic phosphate in the plasma. They assumed 1 Isotopic molecules (-substance) --all the molecules (substance) containing the particular isotopic atom.Labeled atoms (-molecules, -substance) = all the atoms (molecules, substance) mixed with, and chemically indistinguishable from, the isotopic atoms (-molecules, -substance).

Selection and Characterization of [alpha]-Methyltryptophan-Resistant Lines of Lemna gibba Showing a Rapid Rate of Indole-3-Acetic Acid Turnover

“…As previously discussed (Zilversmit et al, 1943;Epstein et al, 1980;Nonhebel and Cooney, 1990), use of this equation assumes that the change in isotope ratios obeys first-order kinetics and that the labeled material is metabolized at a rate similar to that of the unlabeled material.…”

The metabolic clearance of glucose: measurement and meaning

“…Tracers have long been used to determine fluxes of glucose both in [31][32] and out of steady-state [33][34][35]. The essential characteristics of a glucose tracer are: (a) it is present in quantities that are so small that it has no effect on glucose kinetics, (b) it can be separately measured: the glucose is labelled with H 3, H 2, C 14 or C 13 and the concentration of labelled glucose determined by liquid scintillation counting or mass-spectrometry, (c) its kinetic and chemical behaviour is exactly analogous to that of glucose, and (d) it is administered at an entry point equivalent to that of the endogenous or exogenous glucose.…”

Wound Healing and Collagen Formation

“…With these data one can ask whether there is conformation to some particular conceptual model, and utilize, with appropriate provisos, the available kinetic formulation (38,40). Zilversmit et al (43) made the early attempts at evaluation of precursor-product relationship by tracer kinetic analysis. Others have modified and extended this.…”

“…Providing certain initial assumptions are fulfilled one can use these formulations to make presumptive or probable statements about systems in which appropriate measurements can be made (40). The assumptions in the original formulation (43) are that (a) the amount of material present in the system is constant during the interval over which the measurements are made, (b) the rate of flux between the compartments is constant during the time interval of measurement, and (c) molecules are treated randomly.…”