Binding of copper to mucosal transferrin and inhibition of intestinal iron absorption in rats

Abstract

1. The chromatographic elution patterns on Sepharose 6B of the supernatant from mucosal homogenates prepared 10 min after administration of copper into duodenal segments in vivo, indicate that copper is bound preferentially in the fraction of mucosal transferrin. 2. In iron deficiency the amount of 64Cu-copper taken up into the duodenal mucosa is more than two times higher and the amount bound to proteins of the supernatant is also increased to approximately the same degree whereas the amount transferred into the body is diminished to one fourth. 3. In the iron deficient group 64Cu-copper was also bound to a fraction which contains probably metallothionein. 4. The distribution of copper in the supernatant was changed due to a simultaneous administration of iron; the amount of copper bound in the transferrin fraction decreased in favor of the metallothionein fraction and another copper binding fraction was eluted between the transferrin and the metallothionein fraction. 5. Copper in a tenfold molar excess inhibited the iron absorption; simultaneously, the iron bound in the iron binding fractions of the supernatant was remarkably diminished. 6. The results suggest that the affinity of copper to two mucosal iron binding proteins, transferrin and metallothionein, is at least partly responsible for the inhibitory effect of copper on iron absorption in iron deficiency.

Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver

“…These authors also showed, in duodenal loop experiments, that lack of DMT1 impaired copper absorption in iron-deficient (i.e., Belgrade) rats (as compared to normal littermate controls). DMT1 could thus, at least in part, mediate increased copper transport into duodenal enterocytes during iron deprivation, which would support the observation that copper content increased in the duodenal epithelium during ID (78, 248). Given these disparate results, further experimentation and documentation is required to establish a possible role of intestinal DMT1 in copper homeostasis during ID, and during physiological (and possibly pathological) conditions in other mammalian species (besides mice).…”

Molecular Mediators Governing Iron-Copper Interactions

“…Jiang et al (49) also used the DMT1-overexpression HEK293 cell model as well as a complementary ex vivo duodenal loop model to provide evidence that DMT1 transports copper specifically during iron deprivation. These observations suggest that DMT1 could, at least in part, mediate noted increases in copper content of the intestinal epithelium in rodent models of iron deficiency (22, 97). However, further experimentation is required before a consensus can be reached regarding a physiological role for DMT1 in copper homeostasis.…”

“…HIF signaling in the intestine is of particular interest because copper was shown to be required for transactivation of gene expression by the HIF transcriptional complex (which contains a hypoxia-responsive HIFα subunit and a constitutively expressed HIFβ subunit) (24, 69). It may then be logically postulated that increased copper levels in enterocytes (22, 97), in the liver, and in the blood (17, 21) potentiate HIF activity, leading to transactivation of genes that participate in intestinal (and whole-body) iron homeostasis. Interestingly, the HIFα subunits are also stabilized by iron deprivation in vivo and in vitro (83).…”

“…Studies in iron-deficient rats, however, found no increase in whole-body copper levels (87). It could thus be that the copper accumulating in the intestinal mucosa (22, 97) and liver is not released into the blood circulation but rather has localized effects on iron homeostasis. Alternative explanations for liver copper loading are that biliary copper excretion is impaired, cuproenzyme (e.g., CP) synthesis is perturbed, or mobilization of copper from the liver is otherwise altered during iron deficiency.…”

Chelated minerals for poultry

“…The competition between iron and copper is typical: they share at least two membrane proteins, transferrin and metalotionein. Excessive copper bound to those protein may lead to iron deficiency (El Shobaki & Rummer, 1979).…”