Disorders of Bilirubin Metabolism

Bilirubin is the end product of degradation of the heme moiety of hemoproteins. Hemoglobin, derived from senescent erythrocytes, is the major source of bilirubin. Significant fractions are also derived from other hemoproteins of liver and other organs. Historically, hyperbilirubinemia has attracted the attention of clinicians as a marker of liver dysfunction. Subsequently, the studies of bilirubin chemistry, synthesis, transport, metabolism, distribution, and excretion have provided important insights into the transport, metabolism, and excretion of biologically important organic anions, particularly those with limited aqueous solubility. Bilirubin is potentially toxic, but is normally rendered harmless by tight binding to albumin, and rapid detoxification and excretion by the liver. Patients with very high levels of unconjugated hyperbilirubinemia are at risk for bilirubin encephalopathy (kernicterus). Kernicterus is found in some cases of severe neonatal jaundice and in inherited disorders associated with severe unconjugated hyperbilirubinemia. This chapter provides a brief review of bilirubin metabolism and its inherited disorders. N. Roy Chowdhury: Department of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461. I. M. Arias: Departments of Physiology and Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111. A. W. Wolkoff: Departments of Medicine and Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461-1602. J. Roy Chowdhury: Department of Medicine and Molecular Genetics, Albert Einstein College of Medicine Liver Center; Department of Medicine, Jack D. Weiler Hospital of Albert Einstein College of Medicine, Bronx, New York 10461. Fate of Bilirubin in the Gastrointestinal Tract 296 Alternative Routes of Bilirubin Elimination 297 Antioxidant Property of Bilirubin 297