Better Rap for Bilirubin

Frontlines | Better Rap for Bilirubin

Erica P. Johnson

The yellow bile pigment bilirubin has a bad reputation. The normal end-product of hemoglobin breakdown, in excess it causes jaundice, lethargy, seizures, and death. Yet, people with only slightly elevated levels are less prone to heart disease. Neuroscientist Solomon Snyder and colleagues at Johns Hopkins Medical School in Baltimore discovered why the body makes bilirubin at all, when its immediate precursor, biliverdin, is easily excreted: Bile is a powerful, if fleeting, antioxidant (D.E. Barañano et al., "Biliverdin reductase: A major physiologic cytoprotectant," Proc Natl Acad Sci, 99:16093-8, Dec. 10, 2002).

Using RNAi to block the enzyme that interconverts biliverdin and bilirubin doomed the human and rat cells exposed to oxygen radicals. But restoring enzyme function enabled the cells to withstand a 10,000-fold increase in peroxide concentration. Snyder explains that the bilirubin is continuously recycled to keep it functional. "As soon...