010915 heme catab, bile salts Flashcards
where is heme catabolized
macrophage
how is heme broken down?
heme ring opens
heme is converted to biliverdin and then bilirubin
liver’s role in heme breakdown
it takes bilirubin from the blood and conjugates it with glucuronic acid so that it can be excreted in bile
how is urobilinogen made?
by bacteria in the GI tract that remove glucuronic acid from conjugated bilirubin and convert it to urobilinogen
how is urobilin made?
kidney converts urobilinogen to urobilin, which is excreted in urine
first step of heme degradation uses what enzyme
heme oxygenase
conversion of biliverdin to bilirubin is catalyzed by
biliverdin reductase
once inside the hepatocyte, what happens to bilirubin?
bound to ligandin
undergoes conjugation
conjugation of bilirubin is catalyzed by
UGT1A1 (uridine diphosphate glucuronosytransferase)
action of UGT1A1
either one or two glucuronic acid moieties are transferred to bilirubin yielding BMG or BDG
purpose of conjugation of bilirubin
so it’s more water soluble and can be secreted into bile
hyperbilirubinemia can be divided into two classes-what are they?
disorders of unconjugated and conjugated type
neonatal jaundice is due to a combo of what 3 factors?
LOW ACTIVITY OF UGT1A1
decreased excretory capacity of hepatocytes
increased bilirubin production secondary to accelerated destruction of fetal erythrocytes
in most cases, neonatal jaundice is innocuous however
kernicterus appears in
neonatal jaundice due to high levels of UNCONJUGATED bilirubin in the brain
tx for neonatal jaundice
phototherapy (changes unconjugated bilirubin to a form that can be excreted in bile)
inherited unconjugated hyperbilirubinemia
Crigler-Najjar type I, type II
Gilbert Syndrome
(Crigler Najjar type I is most severe by no UDP glucuronsyltransferase activity)
conjugated hyperbilirubinemia–genetic causes?
Dubin Johnson
Rotor Syndrome
hemolytic cause of jaundice results in excess what?
unconjugated bilirubin
bile acids are made from
cholesterol
where are bile acids made
liver
a major mechanism through which cholesterol is excreted
bile acids
how are bile salts formed
primary and secondary bile acids are reabsorbed by the lower ileum into portal blood and taken up by hepatocytes to be conjugated to glycine or taurine, forming bile salts
familial hypercholesterolemia-defect is in?
gene encoding LDL receptor
tx of FH heterozygotes
bile acid binding resins
HMG Coa reductase inhibitors (statins)
diet low in cholesterol and fats
