BUFFALO, N.Y. -- Iron is the workhorse of trace minerals. An
essential component of red blood cells, disruption of iron levels
in the body will result in a myriad of serious conditions, and life
cannot be sustained without it.
In novel research, investigators at the University at Buffalo's
School of Public Health and Health Professions, have learned that
iron is only one half of an all-important duo of trace minerals --
the other being copper -- that work in tandem to maintain proper
iron balance, or homeostasis.
It appears the workhorse has a helper.
James F. Collins, Ph.D., UB assistant professor of exercise and
nutrition sciences and biochemistry, discovered that when
iron-absorption by cells lining the small intestine decreases
during iron-deficient states, copper absorption increases.
Collins now is exploring the relationship between these two
trace minerals through a $1.38 million grant from the National
Institute of Diabetes and Digestive and Kidney Diseases
The work will be carried out using established models of
intestinal iron absorption in humans, including iron and
iron/copper-deficient rodents and cultured intestinal epithelial
"This project is intended to test the overall hypothesis that
increased copper transport during iron-deficiency is critical to
enhance certain aspects of intestinal iron absorption," said
"Iron or copper deficiency causes anemia, and abnormal
intestinal iron transport is associated with several common human
pathologies, including anemia of chronic disease (ACD) and
hereditary hemochromatosis (HH), different forms of which result
from several common genetic defects."
HH is an inherited metabolic disorder characterized by
abnormally high absorption of dietary iron, which is deposited in
body tissues and organs, where it may become toxic. ACD is a blood
disorder caused by low body iron levels resulting from any medical
condition that affects the production and lifespan of red blood
cells, such as chronic infection, chronic immune activation
resulting in inflammation, or malignancy.
"In collaboration with Dr. Zihua Hu, Ph.D., a computational
scientist at UB's New York State Center of Excellence in
Bioinformatics and Life Sciences, we determined that several genes
related to iron and copper homeostasis were strongly induced by
iron deprivation across different developmental stages in the rat
small intestine," said Collins. "We will concentrate on
understanding the role of two key proteins encoded by these genes:
an intestinal iron transporter called divalent metal transporter 1
(Dmt1) and an intestinal copper transporter, the Menkes copper
The overall goal of the project is to answer three specific
questions regarding the role of copper in intestinal iron
transport, Collins noted: 1) Are Atp7a and Dmt1 solely responsible
for enhancing dietary copper absorption during iron-deficiency? 2)
What are the molecular mechanisms leading to induction of the Atp7a
and Dmt1 genes? and 3) Which physiological processes related to
intestinal iron ion homeostasis are enhanced by increased copper
levels in enterocytes (cells of the superficial layer of the
intestines) and in the liver?
"We also expect to learn more about the mechanisms of dietary
copper absorption, which currently are not well defined," Collins
said. "Furthermore, studies addressing the impact of increased
enterocyte and liver copper levels during iron-deficiency have not
been reported in the scientific literature to date, so this
investigation is novel. "
Key collaborators at UB are Hu, Michael D. Garrick, Ph.D.,
professor of biochemistry, and Laura M. Garrick, Ph.D., research
associate professor of biochemistry.
The University at Buffalo is a premier research-intensive
public university, the largest and most comprehensive campus in the
State University of New York. UB's more than 27,000 students pursue
their academic interests through more than 300 undergraduate,
graduate and professional degree programs. Founded in 1846, the
University at Buffalo is a member of the Association of American
Universities. The School of Public Health and Health Professions is
one of five schools that constitute UB's Academic Health