Award details

Role of Dcytb in dietary iron absorption

Reference	BB/F003056/1
Principal Investigator / Supervisor	Professor Andrew McKie
Co-Investigators / Co-Supervisors	Dr Robert Simpson
Institution	King's College London
Department	Nutritional Sciences c
Funding type	Research
Value (£)	379,430
Status	Completed
Type	Research Grant
Start date	01/05/2008
End date	30/06/2011
Duration	38 months

Abstract

The absorption of dietary non haem iron involves at least two proteins present on the brush border membrane, a divalent metal transporter (DMT1) and a ferric reductase (Dcytb) and at least two proteins located on the basolateral membrane a ferrous iron transporter (Ferroportin) and a multicopper oxidase (Hephaestin). Dcytb mRNA and protein levels in the duodenal enterocyte are highly up-regulated by iron deficiency and in iron overload diseases where iron absorption is increased such as haemochromatosis. An initial study of Dcytb KO mice has suggested that Dcytb may not be required for iron absorption under normal conditions however may be important in iron limiting conditions. The lack of phenotype in mice fed a normal diet may be explained by several factors including: genetic strain; dietary iron content and chemical form; up-regulation of other duodenal ferric reductases; release of luminal reducing factors such as ascorbate. We aim to investigate these questions by measuring duodenal ferric reducatse activity and iron absorption in Dcytb KO mice under normal and iron deficient conditions, breeding Dcytb KO mice onto other strains of mice more susceptible to iron deficiency and investigating the role of ascorbate and other reductases in iron absorption.

Summary

Iron is an essential nutrient required by our bodies to make red blood cells and enzymes involved in energy production in our muscles. Eating a diet poor in iron leads to anaemia (lack of haemoglobin in red blood cells) and changes in energy metabolism leading to tiredness and fatigue. It is estimated by WHO that iron deficient anaemia affects millions of people worldwide. On the other hand, too much iron is also a health problem as in the disease haemochromatosis, where too much iron is absorbed from the diet leading to iron accumulation in tissues including the liver, heart and pancreas. Excess iron is toxic to cells causing organ damage. Therefore iron absorption from the diet must be tightly controlled. Over the past few years medical advances have identified several proteins expressed in the gastrointestinal tract that are responsible for absorption of dietary iron. These proteins are regulated by the body's iron stores so that we absorb the correct amount of iron from our diet. Our work aims to study one of these proteins (named Dcytb for duodenal cytochrome b). By studying iron absorption in mice in which the Dcytb gene has been lost we will increase our understanding of absorption of an essential nutrient.

Committee	Closed Committee - Agri-food (AF)
Research Topics	Diet and Health
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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