1. Krista Chau Walter Gao Sarah Son Kin Wong PHM142 Fall 2014 Instructor: Dr. Jeffrey Henderson

2.  Yellow waste product from metabolism of heme  Open chain of tetrapyrrole  Known as bile pigment

3.  80% degradation of heme in hemoglobin  20% myoglobin, cytochrome, catalase

4.  Oxidative cleavage by heme oxygenase, resulting in bilverdin  Reduction by biliverdin reductase, resulting in unconjugated bilirubin

5.  Conjugated bilirubin enters bile and is secreted into the small intestines  Some urobilinogen is reabsorbed into the liver

6.  Urobilinogen is converted to uribilin and excreted with urine  Most of the urobilinogen in the intestine is converted to stercobilin and excreted in feces

8.  Downregulation or inhibition of heme oxygenase and biliverdin reductase

9.  Increased production of bilirubin ◦ Acute hemolytic crises causes greater breakdown of heme  Erythropoiesis

10. Oh no! I’m lacking UDP- glucoronosyltransferase (UGT)! Oh no! I’m missing transporters to uptake bilirubin!  Impaired Conjugation Crigler-Najjar Syndrome Gilbert’s Syndrome  Impaired hepatic uptake

11.  Liver or hepatocyte transplants  Cytochrome P450 inducers ◦ Phenobarbital  Phototherapy ◦ Wavelengths of 400-500 nm

12.  Rate of secretion or flow of bile is obstructed  Hepatitis or biliary obstructions ◦ Invasive treatments are preferred BILE

13.  Fox, S. “Human Physiology.” 12e. 2011.  Kapitulnik, J. “Bilirubin: An Endogenous Product of Heme Degradation with Both Cytotoxic and Cytoprotective Properties.” Molecular Pharmacology. 2004. http://molpharm.aspetjournals.org/content/66/4/773  Leach, T. “Bilirubin Metabolism and Jaundice.” AlmostADoctor. 2014. http://almostadoctor.co.uk/content/systems/-gastrointestinal-tract/liver/bilirubin- metabolism-and-jaundice.  Nazer, H. and J. Katz. “Unconjugated Hyperbilirubinemia.” Medscape. 2013. http://emedicine.medscape.com/article/178841-overview.  Nelson, D.L., and M.M. Cox. “Principles of Biochemistry.” 5e. 2008.  Ophardt, C. “Hemoglobin Catabolism and Bilirubin.” Virtual Chembook. 2003. http://www.elmhurst.edu/~chm/vchembook/634bilirubin.html.  Weisiger, R.A., and J. Katz. “Conjguated Hyperbilirubinemia.” Medscape. 2013. http://emedicine.medscape.com/article/178757-overview.  Voet, D., J.G. Voet, and C.W. Pratt. “Fundamentals of Biochemistry: Life at the Molecular Level.” 4e. 1999.

14.  Bilirubin is a waste product formed from the catabolism of heme, using the enzymes heme oxygenase and biliverdin reductase.  In the liver, unconjugated bilirubin which is insoluble in water is conjugated with glucuronic acid by the enzyme UGT to form the soluble (conjugated) bilirubin.  Bilirubin is converted to microbial enzymes into urobilinogen and oxidized to stercobilin to be excreted in feces.  Urobilinogen can also be reabsorbed from intestines and converted to urobilin to be excreted in urine  Unconjugated hyperbilirubinemia is caused by increased production of bilirubin, impaired conjugation or impaired hepatic uptake  Conjugated hyperbilirubinemia is caused by hepatic or biliary obstructions  Gilbert's syndrome is the most common hereditary cause of hyperbilirubinemia, and is found in up to 5% of the population. It is caused by elevated levels of unconjugated bilirubin in the bloodstream as  a result of reductions in glucuronyltransferase.