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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fre1p is a metalloreductase in the yeast plasma membrane that is essential to uptake of environmental Cu2+ and Fe3+. Fet3p is a multicopper oxidase in this membrane essential for high affinity iron uptake. In the uptake of Fe3+, Fre1p produces Fe2+ that is a substrate for Fet3p; the Fe3+ produced by Fet3p is a ligand for the iron permease, Ftr1p. Deletion of FET3 leads to iron deficiency; this deletion also causes a copper sensitivity not seen in wild type. Deletion of FTR1 leads to copper sensitivity also. Production in the ftr1delta strain of an iron-uptake negative Ftr1p mutant, Ftr1p(RAGLA), suppressed this copper sensitivity. This Ftr1p mutant supported the plasma membrane targeting of active Fet3p that is blocked in the parental ftr1delta strain. A ferroxidase-negative Fet3p did not suppress the copper sensitivity in a fet3delta strain, although it supported the plasma membrane localization of the Fet3p.Ftr1p complex. Thus, loss of membrane-associated Fet3p oxidase activity correlated with copper sensitivity. Furthermore, in vitro Cu1+ was shown to be an excellent substrate for Fet3p. Last, the copper sensitivity of the fet3delta strain was suppressed by co-deletion of FRE1, suggesting that the cytotoxic species was Cu1+. In contrast, deletion of CTR1 or of FET4 did not suppress the copper sensitivity in the fet3delta strain; these genes encode the two major copper transporters in laboratory yeast strains. This result indicated that the apparent cuprous ion toxicity was not due to excess intracellular copper. These biochemical and physiologic results indicate that at least with respect to cuprous and ferrous ions, Fet3p can be considered a metallo-oxidase and appears to play an essential role in both iron and copper homeostasis in yeast. Its functional homologs, e.g. ceruloplasmin and hephaestin, could play a similar role in mammals.
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PMID:Fre1p Cu2+ reduction and Fet3p Cu1+ oxidation modulate copper toxicity in Saccharomyces cerevisiae. 1295 29

Iron deficiency during pregnancy causes problems both for the mother and fetus. Iron deficiency is known to have secondary effects on copper metabolism. In this study, we use a rat model to examine the effect of iron deficiency on copper levels in maternal and fetal tissue. We assess whether the effects of iron deficiency on copper metabolism are due to alterations in mRNA levels of proteins of copper transport. Rowett Hooded Lister rats were fed diets with four different iron contents before and during pregnancy. Maternal and fetal samples were collected on day 21 of gestation. Copper and iron levels of liver and placenta were analyzed, mRNA levels of genes involved in copper transport were studied, and copper oxidase activity measured. Reduced dietary iron was found to increase maternal liver copper, inversely correlating with iron levels. Correspondingly, copper and ceruloplasmin increased in maternal serum. The placenta showed the greatest increase in copper levels. As the iron content of the maternal diet decreased so did the iron and copper levels in the fetal liver. In all tissues examined, mRNA expression for CTR1, ATOX1, ATP7A, and ATP7B was unchanged by iron deficiency. However, copper oxidase activity in maternal serum and placenta was increased. Our study in a rat model demonstrates that iron deficiency during pregnancy has a differential effect on copper metabolism in the mother and fetus. It is clear from this study that the changes in copper levels that accompany iron deficiency are not mediated by changes in transcription of the genes involved in copper transport.
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PMID:Iron deficiency in the pregnant rat has differential effects on maternal and fetal copper levels. 1515 43