Antony F. McDonagh

Bilirubin, the end product of heme catabolism in mammals, is generally regarded as a potentially cytotoxic, lipid-soluble waste product that needs to be excreted. However, it is here that bilirubin, at micromolar concentrations in vitro, efficiently scavenges peroxyl radicals generated chemically in either homogeneous solution or multilamellar liposomes. The antioxidant activity of bilirubin increases as the experimental concentration of oxygen is decreased from 20% (that of normal air) to 2% (physiologically relevant concentration). Furthermore, under 2% oxygen, in liposomes, bilirubin suppresses the oxidation more than alpha-tocopherol, which is regarded as the best antioxidant of lipid peroxidation. The data support the idea of a "beneficial" role for bilirubin as a physiological, chain-breaking antioxidant.

A newborn male infant is brought to the pediatrician's office with pronounced jaundice and a total serum bilirubin level of 19.5 mg per deciliter. Phototherapy is considered. In term and late-preterm infants, phototherapy is typically used according to guidelines that take into account the total serum bilirubin level, gestational age, postpartum age, and the presence or absence of specific risk factors.

Bilirubin, an insoluble yellow-orange pigment derived from heme catabolism, accumulates to toxic levels in individuals with impaired or immature liver function. The resulting jaundice may be managed with phototherapy to isomerize the biosynthetic 4Z,15Z-bilirubin-IXalpha to more soluble and excretable isomers, such as 4Z,15E-bilirubin. Bilirubin and its configurational isomers are transported to the liver by human serum albumin (HSA) but their precise binding location(s) on the protein have yet to be determined. To investigate the molecular details of their interaction, we co-crystallised bilirubin with HSA. Strikingly, the crystal structure--determined to 2.42 A resolution--revealed the 4Z,15E-bilirubin-IXalpha isomer bound to an L-shaped pocket in sub-domain IB. We also determined the co-crystal structure of HSA complexed with fusidic acid, an antibiotic that competitively displaces bilirubin from the protein, and showed that it binds to the same pocket. These results provide the first crystal structure of a natural bilirubin pigment bound to serum albumin, challenge some of the present conceptions about HSA-bilirubin interactions, and provide a sound structural framework for finally resolving the long-standing question of where 4Z,15Z-bilirubin-IXalpha binds to the protein.

Research Article| September 01 1972 The ready isomerization of bilirubin IX-α in aqueous solution A F McDonagh; A F McDonagh Search for other works by this author on: This Site PubMed Google Scholar F Assisi F Assisi Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1972) 129 (3): 797–800. https://doi.org/10.1042/bj1290797 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation A F McDonagh, F Assisi; The ready isomerization of bilirubin IX-α in aqueous solution. Biochem J 1 September 1972; 129 (3): 797–800. doi: https://doi.org/10.1042/bj1290797 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1972 London: The Biochemical Society1972 Article PDF first page preview Close Modal You do not currently have access to this content.