The Effect of No and Co on Cellular Iron Metabolism: a Comparison of Two Diatomic Cell Signalling Molecules

Nitric oxide (NO) and carbon monoxide (CO) are toxic gases in the atmosphere that are usually associated with pollution. Surprisingly, both have been found to be synthesised within the body and have functions as signalling molecules. It has been shown that they actuate their signal by interacting with iron (Fe) in Fe-containing proteins. Fe is an obligate requirement for cells as many important enzymatic proteins utilise this element for redox activity. Activated macrophages produce large quantities of NO and it has been hypothesised that one of the cytotoxic mechanisms of activated macrophages is the NO crossing into the target cell and removing the Fe from the proteins and effluxing it from the cell. CO also interacts with Fe, but its effects on cellular Fe metabolism have not been examined in as great detail as NO has. This work has examined the effects of NO donors and CO gas and donors on cellular Fe metabolism. It describes the pathway NO utilises in its removal of Fe from cells and compares these results with CO. It indicates that although both molecules interact with Fe they have different effects on cellular Fe metabolism.