Post on 16-Dec-2015
Disturbances in Bilirubin Metabolism
Krista ChauWalter Gao
Sarah SonKin Wong
PHM142 Fall 2014 Instructor: Dr. Jeffrey Henderson
What is Bilirubin?
Yellow waste product from metabolism of heme
Open chain of tetrapyrrole
Known as bile pigment
Where Bilirubin is Made
80% degradation of heme in hemoglobin
20% myoglobin, cytochrome, catalase
How Bilirubin is Made
Oxidative cleavage by heme oxygenase, resulting in bilverdin
Reduction by biliverdin reductase, resulting in unconjugated bilirubin
Conjugation
Conjugated bilirubin enters bile and is secreted into the small intestines
Some urobilinogen is reabsorbed into the liver
Excretion
Urobilinogen is
converted to uribilin and
excreted with urine
Most of the urobilinogen
in the intestine is
converted to stercobilin
and excreted in feces
Hypobilirubinemia
Downregulation or inhibition of heme oxygenase and biliverdin reductase
Unconjugated Hyperbilirubinemia
Increased production of bilirubin
◦Acute hemolytic crises causes greater breakdown of heme
Erythropoiesis
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
How can we treat Jake the liver?
Liver or hepatocyte transplants
Cytochrome P450 inducers
◦Phenobarbital
Phototherapy
◦Wavelengths of 400-500 nm
Conjugated Hyperbilirubinemia
Rate of secretion or flow of bile is obstructed
Hepatitis or biliary obstructions
◦ Invasive treatments are preferred
BILE BILE
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.
References
Summary 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.