Short-term measurement of catabolic rates using iodine-labeled plasma protein

Fractional catabolic rates of iodine-labeled plasma albumins and fibrinogens have been measured in experiments of a few hours duration in adult rabbits. The method used which is based on release of labeled iodide from the protein gives accurate estimates of catabolic rates (expressed as fractions of the plasma protein pool catabolized per day) after 36 hr without the need for urine collections. At earlier times and using undenatured albumin, fractional catabolic rates increased steadily from approximately 10% per day in the first few hours to a constant 20-25% per day after 24 hr. Fibrinogen values which started at 15% plateaued after 24 hr at 30-35% per day. The fractional synthesis rate of albumin, measured with (14)C-labeled carbonate in the first 6 hr when the short-term fractional catabolic rate was 10.2% agreed with the 36 hr plateau value of 29% per day. The presence of traces of denatured or polymerized proteins was revealed by high initial fractional catabolic rates, and in a few experiments biological screening in another animal was not fully effective in removing them. On the other hand, some labeled albumins showed no traces of denatured protein even without biological screening. Fibrinogen polymer was catabolized rapidly and behaved like denatured or incipiently clotted fibrinogen. Irradiation of albumin produced a marked increase in early fractional catabolic rates, and some proteins after prolonged storage and labeling behaved similarly. Alternative theories to explain the low fractional catabolic rates in the first 24 hr are considered. Since radioautographic experiments failed to provide evidence for retention of labeled proteins or their nondiffusible breakdown products inside catabolic cells, preference is given to the view that catabolism occurs in a pool of significant protein content which is either a subunit of the extravascular pool or is independent and sandwiched between the plasma and extravascular pools. Earlier hypotheses concerning small catabolic pools in which protein specific activities approximate closely to plasma values at the same time are considered to be no longer tenable.