Haem's secret life as a hormone exposed

Researchers in the US have found that haem, the iron-containing molecule best known for its role as the oxygen-carrier in haemoglobin, may act as a hormone.¹ 

The groups of Fraydoon Rastinejad at the University of Virginia at Charlottesville and Thomas Burris at the Pennington Biomedical Research Center at Baton Rouge, Louisiana, have found that haem ’switches on’ two proteins that are part of a family of receptors normally activated by hormones. 

REV-ERBalpha and REV-ERBbeta are known to regulate the body’s circadian clock² but before the discovery no-one had pinned down a chemical trigger for either receptor. According to the researchers, the two proteins are purely sensing haem - and not oxygen or other gases bound to its iron atom. 

The work also links the biological clock to metabolism, as more haem is produced when the body burns fat. 

The authors are optimistic that their discovery will help pave the way to new drugs. ’[This finding] allows us to envision a tremendous range of potential medical applications,’ Burris said. Modified versions of haem, he suggests, could one day be used to treat sleep problems or metabolic disorders. 

Ueli Schibler of the University of Geneva, who first linked the REV-ERB receptors to the circadian clock, welcomed the findings. ’The binding of haem to REV-ERBs is very interesting, but not completely unexpected,’ he added. ’The Drosophila homolog E75 has been shown to bind haem two years ago.³ Nevertheless, there is definitely some romance in this discovery, as it will incite many researchers to uncover the function of haem binding.’ 

However, scientists contacted by Chemistry World dispute the idea that haem is acting as a hormone. ’In this context I would regard haem an intracellular ligand, rather than a hormone,’ Schibler said. 

Burris admits that there is no evidence so far that haem conveys information from one type of cells to another, as most hormones do. ’Although the classical definition of being secreted by one cell type, travelling to another cell type by blood is the most common definition... hormones have also been described where the hormone is produced within the same cell it acts,’ he told Chemistry World. 

Michael Gross