Intracellular Aspects of Transferrin Synthesis and Secretion in the Rat

The incorporation of 14C-leucine in vivo into transferrin within rat liver cell fractions and in the blood stream has been measured and compared with that of serum albumin. The rate of transferrin production as measured by two techniques was about 0.13 mg per g of liver per hour, one-fifth the rate of albumin production. Both proteins are apparently synthesized directly from the pool of free leucine in the liver, but it takes about 2 min to form a molecule of transferrin in contrast to 1 min for an albumin molecule. Like albumin, transferrin remains bound to cytoplasmic membranes until its secretion into the circulation. The secretion of newly formed transferrin is a slower process than that of albumin, requiring a minimum time of about 30 min and an average of about 80 min. The amount of transferrin found in microsomes was correspondingly larger relative to its rate of production than the amount of albumin; the levels obtained by an immunochemical technique were 320 and 390 µg per g of liver, respectively. From the shapes of the curves of microsomal radioactivity, it is proposed that newly synthesized proteins migrate through the channels of the endoplasmic reticulum in an orderly sequence, but that some randomization of molecules of different ages occurs at a stage prior to secretion.