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Correcting Iron-delivery Defects in Animals

Scientists recently identified a small molecule compound capable of correcting iron-delivery defects in animal models. Iron is essential to the body’s oxygen-delivery system. Humans need iron to make hemoglobin, the oxygen-carrying molecule in red blood cells. Iron is shuttled to various tissues of the body by an exquisitely well-controlled series of proteins called iron transporters. Defects in iron delivery can lead to too little iron (also called iron deficiency anemia) or a buildup of too much iron (also called hemochromatosis) and are associated with more than 25 human diseases. Thus, approaches that restore normal iron delivery would be beneficial to those with these conditions.

The researchers began by studying iron transport in baker’s yeast, an organism readily amenable to experimentation. While evaluating a series of candidate compounds for their ability to restore growth capacity to yeast missing a specific iron transport protein, researchers discovered that the natural product hinokitiol—originally isolated from the essential oil of a tree—restored normal growth rates. After showing that hinokitiol binds tightly to two forms of iron (ferrous and ferric) found in cells, the investigators demonstrated that this small molecule had the inherent ability to transport both ferrous and ferric iron across a model cell membrane. Further studies suggested that hinokitiol dissipates iron buildup by transporting iron from areas of high iron concentration to areas of low concentration. In a set of experiments in mice and rats genetically engineered to lack specific iron transport proteins in the gut, the researchers showed that orally administered hinokitiol restored iron uptake in the animals. The researchers also demonstrated that hinokitiol restored normal hemoglobin production in zebrafish lacking a specific iron transport protein. This suggests that hinokitiol can work with the body’s existing regulatory systems to supply iron where it is needed without interfering with other cell functions.

The findings from this study suggest that small molecules like hinokitiol may one day be used to substitute for missing or defective human iron transport proteins. More research into hinokitiol’s function and safety will be needed to explore this fascinating possibility.

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