Biliverdin targets enolase and eukaryotic initiation factor 2 (eIF2α) to reduce the growth of intraerythrocytic development of the malaria parasite Plasmodium falciparum

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. In mammals, haem degradation to biliverdin (BV) through the action of haem oxygenase (HO) is a critical step in haem metabolism. The malaria parasite converts haem into the chemically inert haemozoin to avoid toxicity. We discovered that the knock-out of HO in P. berghei is lethal; therefore, we investigated the function of biliverdin (BV) and haem in the parasite. Addition of external BV and haem to P. falciparum-infected red blood cell (RBC) cultures delays the progression of parasite development. The search for a BV molecular target within the parasites identified P. falciparum enolase (Pf enolase) as the strongest candidate. Isothermal titration calorimetry using recombinant full-length Plasmodium enolase suggested one binding site for BV. Kinetic assays revealed that BV is a non-competitive inhibitor. We employed molecular modelling studies to pr...

Vitamin E Succinate Continues to Show Impressive Anti-Cancer Properties

Several recent short-term intervention studies failed to show vitamin E supplementation was protective against the development of various cancers, most notably lung and prostate cancer. In fact, in the SELECT study, individuals taking vitamin E supplements showed a 17 percent higher incidence of prostate cancer. In the SELECT study, researchers used a synthetic form of vitamin E known as dl-alpha tocopherol acetate. Some experts have argued this form of vitamin E has only half the potency of natural forms of vitamin E, and thus was a poor candidate for use in this and other trials. Others argue synthetic vitamin E competes with natural vitamin E (both tocopherols and tocotrienols) for receptor binding sites and other processes, reducing the cell’s vitamin E antioxidant defenses and/or reducing other anti-cancer effects afforded by natural vitamin E (d-alpha-tocopherol).1-10,19 Still others have implied vitamin E succinate should be the form of vitamin E used in intervention trials aimed at reducing cancer incidence, as it is the form of vitamin E with the strongest current research support as an anti-cancer agent.20 Adding to the confusion are recent studies that suggest ...