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).
With the assistance of B. W. Shumway, Ph.D., and R. Skahen, M.D. 12. LINDSAY, S., AND CHAIKOFF, I. L.: Arteriosclerosis in the baboon: Naturally occurring lesions in aorta and coronary and iliac arteries.
The rates of excretion of taurocholic acid and lipids in the bile of the isolated perfused liver and the bile fistula rat were determined. In the bile fistula rats, there was, during the first 12 hours after cannulation, a fall in the excretion of taurocholic acid, which was then followed by an increase in the rate of excretion. The excretion of free cholesterol and phospholipids followed the same excretion pattern as for taurocholic acid, whereas the biliary excretion of glycerides and cholesterol esters was nearly constant. Livers perfused immediately after cannulation of the bile duct excreted only very small amounts of bile acids and lipids in the bile. On the other hand, when livers were perfused 48 hours after cannulation, the bile acids were excreted at a greatly accelerated rate and increased amounts of free cholesterol and phospholipids appeared in the bile. The infusion of cholic acid into a liver, perfused immediately after cannulation of the bile duct, gave rise to an increased biliary excretion of bile acids, free cholesterol and phospholipids.
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