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Regulation of Synthesis and Turnover of Ferritin in Rat Liver

James W. Drysdale 1 and Hamish N. Munro 1

From the 1 Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, and The Department of Biochemistry, University of Glasgow, W.2, Scotland

Synthesis of liver ferritin induced by iron administration was investigated by treating rats by injection with pulse doses of leucine-14C at various times after a single intraperitoneal dose of iron. The iron caused a rapid but transient increase of leucine uptake into ferritin without affecting incorporation into mixed liver proteins; the ferritin response was dose-dependent and was followed by an increase in liver ferritin content. Since the action of iron was insensitive to actinomycin D, it was considered to be independent of synthesis of new messenger ribonucleic acid.

Ferritin turnover was studied by following loss of radioactivity from liver ferritin over a 72-hour period after leucine-14C administration. Repeated injections of iron during this period increased the iron to protein ratio of ferritin and retarded loss of radioactivity, thus suggesting that iron-rich ferritin molecules are less susceptible than iron-poor molecules to degradation. With the use of a sucrose density gradient to separate ferritin species of differing iron content, it was shown that the first fraction to become labeled after injection of leucine-14C was low in iron. Subsequently there was progressive transfer of the label to ferritin fractions richer in iron over a 72-hour period. Repeated injection of iron caused a larger proportion of the initial radioactivity of the iron-poor fraction to be retained as iron-rich ferritin.

To explain the actions of iron on ferritin metabolism by a single unifying hypothesis, it is proposed that iron can cause an apparent induction by stabilizing an unstable precursor of ferritin which would otherwise be rapidly degraded, and that iron can also stabilize iron-poor ferritin molecules by increasing their iron content and thus retarding their degradation.

Submitted on January 31, 1966


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