Mechanisms Of Intestinal Iron Absorption And Consequences Of Iron Supplementation During The Perinatal Period
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Iron intake is particularly high during pregnancy and in the newborn to meet the requirements of the growing fetus and neonate. While it is widely recommended that women take iron supplements at this time, too much iron may adversely affect pregnancy outcome. The aim of this study is to understand the factors controlling iron intake in the perinatal and the consequences of excess iron. This will provide the physiological information required to make rational decisions about iron supplementation.
The Mechanism Of Intestinal Haem Iron Absorption And Characterization Of A Novel Haem-binding Protein
Funder
National Health and Medical Research Council
Funding Amount
$537,773.00
Summary
Iron is essential for normal health as many important proteins in the body require iron to function properly (e.g. haemoglobin). However, too much iron can be toxic, so the body must keep its iron content within defined limits. The amount of iron in the body is determined at the point of absorption from the diet in the small intestine. If too little iron is absorbed, then anaemia can result. If too much iron is absorbed, as is the case in the common disease haemochromatosis (with approximately 1 ....Iron is essential for normal health as many important proteins in the body require iron to function properly (e.g. haemoglobin). However, too much iron can be toxic, so the body must keep its iron content within defined limits. The amount of iron in the body is determined at the point of absorption from the diet in the small intestine. If too little iron is absorbed, then anaemia can result. If too much iron is absorbed, as is the case in the common disease haemochromatosis (with approximately 1 in 200 Australians at risk) then the body becomes iron loaded and various organs, particularly the liver, can become damaged. An understanding of how iron is absorbed will place us in a much better position to treat diseases such as this. Iron is present in the diet in two forms - inorganic iron and haem iron. Inorganic iron is the main form of iron in foods of plant origin while most haem iron comes from meat. In a typical diet 80-90% of the iron is inorganic iron and only 10-20% is haem. Despite this, 30-50% of the iron taken into the body comes from haem, so haem iron absorption is particularly efficient. While we have learned a great deal about the mechanims by which inorganic iron is absorbed in recent years, we know very little about the absorption of haem iron, so that is the focus of this project. We will study the pathway by which haem enters the body, how this process is regulated, and the characteristics of haem binding to the cells lining the small intestine. These cells are responsible for the uptake of all nutrients from the diet. In particular, we will examine the biology of a recently identified protein known as HCP1. Preliminary evidence suggests that HCP1 could be the main protein enabling haem to be taken up by intestinal cells. These studies will enhance our knowledge of an important nutritional pathway and improve our capacity to treat diseases such as haemochromatosis where iron absorption is defective.Read moreRead less
The Role Of Transferrin Receptor, Divalent Metal Transporter, Ferroportin And Hemochromatosis Protein In Iron Absorption
Funder
National Health and Medical Research Council
Funding Amount
$195,990.00
Summary
Within Australia 1 in 300 people of Caucasian origin have a genetic defect which makes them absorb more iron from the diet than they need. Excess iron is a major problem because it damages cells and this is most obvious in the pancreas where the cells make insulin are destroyed and diabetes mellitus develop. In the liver cirrhosis and cancer often occur. Iron also accumulates in other tissues such as the heart and joints resulting in damage to these organs. The genetic defect has recently been i ....Within Australia 1 in 300 people of Caucasian origin have a genetic defect which makes them absorb more iron from the diet than they need. Excess iron is a major problem because it damages cells and this is most obvious in the pancreas where the cells make insulin are destroyed and diabetes mellitus develop. In the liver cirrhosis and cancer often occur. Iron also accumulates in other tissues such as the heart and joints resulting in damage to these organs. The genetic defect has recently been identified but how the defective protein causes the cells of the intestine to absorb more iron into the body than is needed remains unknown. This has led to the idea that the normal protein is responsible for controlling the amount of iron absorbed. Recent studies have shown a link between this protein and another called transferrin receptor. These two molecules are thought to co-operate in determining how much iron will be absorbed. Once this is determined other molecules called iron transporters are produced and these are responsible for moving the iron from the intestine into the blood. When not much iron is required only a small number of transporters are made and when more iron is required then many more are produced. How these transporters program the level of iron absorption is unknown but the process probably involves the transferrin receptor and the hemochromatosis protein. This project will investigate the function of the molecules that determine the programe for how much iron is to be absorbed, and secondly how this is linked to the production and movement of the transproters that co-ordinate this function.Read moreRead less
The Effect Of Iron Supplementation In Pregnancy On Child Cognitive Development
Funder
National Health and Medical Research Council
Funding Amount
$91,562.00
Summary
During fetal life the brain grows very rapidly and animal studies have shown that inadequate iron nutrition of mothers during pregnancy can result in permanent structural and developmental problems in the offspring. Although this has not been examined in human infants, new studies suggest that the iron stores of the mother in pregnancy are an important determinant of the baby's iron stores during the first year of life. It may be that the critical period where iron nutrition influences later dev ....During fetal life the brain grows very rapidly and animal studies have shown that inadequate iron nutrition of mothers during pregnancy can result in permanent structural and developmental problems in the offspring. Although this has not been examined in human infants, new studies suggest that the iron stores of the mother in pregnancy are an important determinant of the baby's iron stores during the first year of life. It may be that the critical period where iron nutrition influences later development is in fetal life (during pregnancy). We have the opportunity to test whether iron nutrition in fetal life influences childhood development by assessing the cognitive abilities of children who were in our earlier study of iron supplementation in pregnancy. Our aim is to assess the children at 4 years to determine if iron nutrition in pregnancy predicts development. This may change the dietary advice we give pregnant women to ensure they give their babies the best start in life.Read moreRead less
Regulation Of The Nedd4 Family Of Ubiquitin Ligases By Adaptor And Accessory Proteins In Normal Physiology And In Disease
Funder
National Health and Medical Research Council
Funding Amount
$609,424.00
Summary
In part this proposal is to understand how the body controls iron uptake through iron transporters DMT1 and Nramp1. We will study the regulation of these transporters by proteins called Ndfip1, Ndfip2 and arrestins. We will also study the functions of these proteins in controlling ubiquitination, a fundamental process required for cellular homeostasis. The results from this study may ultimately contribute to the development of novel therapies for certain human diseases.
Does Weekly Iron Supplementation Increase Iron Uptake In Pregnant Women And Improve Maternal And Infant Health?
Funder
National Health and Medical Research Council
Funding Amount
$830,171.00
Summary
Anaemia and iron deficiency are common in pregnant women in developing countries and cause fatigue, prematurity, low birth weight, impaired infant groowth and development. Daily iron is recommended in pregnancy but often not taken because of unpleasant side-effects. Better strategies are needed to maintain iron and haemoglobin during pregnancy. We will compare the effect of weekly and daily iron tablets in 1200 pregnant Vietnamese women on anaemia rates, birthweight, maternal and infant health.