AJP - Gastrointestinal and Liver Physiology, Vol 251, Issue 3 398-G404, Copyright © 1986 by American Physiological Society
Preferential hepatic uptake of iron from rat asialotransferrin: possible engagement of two receptors
J. R. Rudolph, E. Regoeczi, P. A. Chindemi and M. T. Debanne
Hepatic iron uptake from and degradation of rat asialotransferrin prepared
from the least anionic (major) component of rat transferrin were studied in
intact rats. In experiments lasting 60-90 min, rat asialotransferrin
delivered a three to four times larger fraction of the Fe dose to the liver
than rat transferrin. Variations in the concentration of endogenous
circulating rat 2Fe-transferrin by up to 300% failed to affect the enhanced
hepatic delivery of Fe from rat asialotransferrin. However, pretreating the
animals with a large dose of asialomucin, or fully sialylated human
transferrin, or a combination of both did affect the delivery. In all
cases, rat asialotransferrin delivered Fe to the liver at rates comparable
with those seen with rat transferrin. The reason for the efficacy of human
transferrin was clarified in competitive binding studies on rat hepatocytes
and reticulocytes, which showed that human transferrin possessed an
approximately sevenfold higher affinity for rat transferrin receptors than
the homologous protein. These findings suggest that the enhanced hepatic
uptake of Fe from rat asialotransferrin is mediated by simultaneous binding
of the ligand both through its glycan and transferrin receptor affinity
site. Pretreatment with asialomucin and human transferrin had no
suppressing effect on basal hepatic delivery of iron from rat
2Fe-transferrin. The data suggest that deposition of a significant fraction
of Fe in rat liver from rat transferrin is likely to take place by a
mechanism not involving transferrin receptors. Desialylation shortened the
metabolic half-life of rat transferrin from 33 to 24 h.(ABSTRACT TRUNCATED
AT 250 WORDS)
