How Dietary Iron Is Used By Cells
A four-year study on iron metabolism within cells,
an essential process that impacts both iron deficiency and iron
toxicity, conditions responsible for a multitude of human diseases,
is underway at the University at Buffalo funded by a $1.16
million grant from the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK).
Daniel Kosman, Ph.D., professor of biochemistry in the UB School
of Medicine and Biomedical Sciences, is lead researcher on the study.
"The concern about how iron is managed in our cells has
never been more acute," said Kosman. "The reasons for
this are three-fold. First is the endemic problem of iron deficiency
that the World Health Organization estimates afflicts 80 percent
of the world's population, or more than 5 billion people.
"Iron deficiency is not confined to developing nations.
In the U.S., 5 percent of newborns and 7 percent of new mothers
have clinical symptoms of iron deficiency. Reducing the incidence
of this nutritional deficit is one of the objectives of the U.S.
Department of Health and Human Services' Healthy People 2010 program.
"Second is the broad recognition that the 'corrosive chemistry'
associated with iron and oxygen interactions is a major factor
in a multitude of human diseases."
Too much iron in tissues, called iron-loading, is thought to
increase the risk of tumor development, infection, cardiomyopathy,
joint disorders and several endocrine and neurodegenerative disorders.
"And third, we now have an increasingly sophisticated knowledge
and understanding of iron metabolic pathways, the proteins involved
in these pathways and how these pathways are regulated in all
organisms, making this issue ripe for investigation," he
Kosman proposes that a general mechanism of cellular iron metabolism
requires that iron-handling proteins involved in sequential steps
in the pathway must be "architecturally arranged" contiguously
in the cell's membranes, at the interfaces between membranes and
soluble compartments or within soluble compartments.
The researchers will test this form-function model of ionic
iron metabolism by focusing on three steps critical to maintaining
the proper balance of iron in cells: 1) the reduction of ferric
to ferrous iron and the subsequent transport of ferrous iron into
a cell; 2) the "hand-off" of this ferrous iron from
a membrane protein to iron chaperones in the cell's cytoplasm;
and 3) the utilization of this ionic iron for the activation of
essential iron-containing enzymes.
"These three components of cellular iron metabolism are
relatively under-investigated," said Kosman, "yet they
represent the essence of cell iron metabolism in all organisms."
Understanding the intermediary metabolism of iron is one of
the primary objectives of a program announcement from NIH titled
"Metals In Medicine," he noted. This announcement encourages
studies that lead to the "identification and characterization
of the macromolecular players and vesicular compartments involved
in metal ion homeostasis and metal trafficking."