Bilirubin Biochemistry

  1. What is the conjugating enzyme that everyone keeps talking about?
  2. High bilirubin level that is less than 20% indicates which cause?
    • Most likely due to hemolysis
    • Rarely is it a liver issue if it is less than 20%
  3. Direct bilirubin measures _____ bilirubin. Indirect measures _____ bilirubin. While total bilirubin test measures_____
    • Conjugated
    • Unconjugated
    • Total measures both conjugated and unconjugated (“indirect” is actually calculated by getting the total bilirubin subtracting direct to get the unconjugated bilirubin)
  4. Conjugated bilirubin is aka _______
    Bilirubin diglucuronide
  5. Notable receptors on the apical membrane of the hepatocyte are (receiving bilirubin from the sinusoids):
    • OATP1B1
    • OATP1B3
  6. Receptors on the basolateral membrane of the hepatocytes are (exporting conjugated bilirubin out to the bile canaliculi):
    • MRP2
    • ABCG2
  7. Most prevalent cause of jaundice is ____. And this causes increased ______ bilirubin
    • Hemolysis (prehepatic jaundice)
    • Indirect (a lot of unconjugated bilirubin)
  8. UDP-glucuronsyltransferase is encoded by which gene?
    UGT1A1 gene
  9. Which syndrome results from mutation to UGT1A1 gene? What is mutated?
    • Gilbert syndrome
    • UDP-glucuronsyltransferase is mutated
  10. Gilbert syndrome is a _____ cause of hyperbilirubinemia, with increased _____ bilirubin, since ___( gene) coding for ____(enzyme) is mutated
    • hepatic
    • Indirect
    • UGT1A1 gene
    • UDP-glucuronsyltransferase
  11. T/F: Gilbert syndrome is autosomal dominant
    False; it is autosomal recessive, loss-of-function
  12. What is Crigler Najjar type 1 syndrome?
    • Autosomal recessive, severe, lethal early in life.
    • Complete or near complete loss of UDP glucuronosyltransferase activity
  13. True//false: Crigler-Najjar type 1 and type 2, Gilbert syndrome are each caused by mutations of the gene UGT1A1 that encodes for UDP glucuronosyltransferase
  14. Syndromes due to loss of function mutations of UGT1A1, rank it from somewhat high bilirubin to lethal level of hyperbilirubinemia:
    • Gilbert (fluctuating high)
    • Crigler-Najjar type 2 (permananetly high)
    • Crigler-Najjar type 1 (lethal)
  15. What is Dubin-Johnson syndrome?
    Caused by autosomal recessive loss-of-function of MRP2 or ABCG2 – which are transporters on the basolateral hepatocyte that ships conjugated bili to the canaliculi en route to the gallbladder
  16. Mutations of MRP2 or ABCG2 receptors is _______ syndrome. This is a ___ Cause of hyperbilirubinemia, with increase ___ test
    • Dubin-Johnson
    • Hepatic
    • Direct
  17. T/F: backup of conjugated bilirubin will also cause some buildup of unconjugated bilirubin in Dubin-Johnson syndrome
  18. What is Rotor syndrome?
    Loss-of-function mutations affecting OATP1B1 and OAT1B3 transporters on the apical membrane
  19. T/F: rotor syndrome leads to increase in Direct bilirubin
    TRUE; weird, but true. This is because there are some sort of hopping action that occurs that still allows conjugated bilirubin to hop to the central vein
  20. These syndromes lead to increased indirect bilirubin:
    Crigler Najjar 1, Crigler-Najjar 2, Gilbert
  21. These syndromes lead to increased direct bilirubin
    • Dubin-Johnson
    • Rotor
  22. Biliverdin is ___ soluble. Bilirubin is _____soluble
    • Water
    • Fat
Card Set
Bilirubin Biochemistry
GI Final- Biochemistry