Heme Flashcards
Where is the majority of heme synthesized?
bone marrow
What other molecule is dependent on the heme pathway for its synthesis?
cytochrome
What two products does heme synthesis begin with?
glycine and succinyl-CoA
What does ALA synthase stand for?
aminolevulinic acid synthase
At what step is heme synthesis exported from the mitochondria?
aminolevulinic acid is exported from the mitochondria
What stage of heme synthesis re-enters the cytosol?
Protoporphyrinogen IX
What is the committed step of heme synthesis?
ALA synthase
What two drugs exacerbate heme synthesis disorders?
alcohol and barbiturates.
induction of cytochrome p450 pathways (MEOS)
What enzyme is affected in acute intermittent porphyria?
PBG deaminase
How does acute intermittent porphyria manifest itself?
patient will present with dark red urine
What enzyme is affected by porphyria cutanea tarda?
UPG III Decarboxylase
How does acute porphyria cutanea tarda manifest itself?
under UV light, urine of patient will emit a red fluorescence
Why can porphyrias cause photosensitivity?
porphyrins can absorb UV and visible light and use that energy to generate reactive oxygen species
What two enzymes of heme synthesis are affected by lead?
PBG synthase and ferrechelatase
What is the half-life of RBCs?
120 days
What two organs remove damaged RBCs?
spleen = majority
liver = some too
Heme oxygenase produces what two by-products?
carbon monoxide and Fe (III)
What reducing equivalent does bilivedin reductase consume?
NADPH
How many UGT molecules are attached to bilirubin?
two
Where is bilirubin produced?
spleen
How does bilirubin travel from the spleen to the liver?
albumin
What do gut bacteria catalyze bilirubin into?
urobilinogen
What else do the bacteria do to bilirubin?
remove the gluronic acid molecules
Oxidation or urobilinogen yields what product?
urobilin (stercobilin)
Where doe the yellow color of urine come from?
urobilins reabsorbed from the gut and renally excreted
At what concentration of bilirubin will it enter the tissues?
2-3 mg/dL
When bilirubin crosses the blood brain barrier, what is this condition called? Is this conjugated or unconjugated bilirubin?
kernicterus
unconjugated
What color of feces or urine indicates a bilirubin conjugation deficiency?
pale
What drug can interfere with bilirubin conjugation?
acetominophen
How does a blocked bile duct lead to jaundice?
impedes liver’s ability to excrete conjugated bilirubin into the feces
What two tenets can suggest cholestatic jaundice?
pale feces and dark urine
What marker is indicative of a blocked bile duct?
alkaline phosphatase in serum
Synthesis of what kind of detoxification enzymes consumes heme? How does this affect heme synthesis?
Cytochrome p450
increases heme synthesis by removing feedback inhibition
How does bilirubin get from the spleen to the liver?
albumin!
Bacterial processing of conjugated bilirubin in the gut produces what compound?
urobilinogens
What else do intestinal bacteria due to conjugated heme?
remove the glucoronic acid molecules
oxidation of urobilinogen yields what?
urobilin (feces color)
What gives urine its color?
reabsorbed urobilinogens from the gut
What is the criteria for diagnosis of hyperbilirubinemia?
1.5 mg/dL
bilirubin enters tissues at 2-3 mg/dL
What type of bilirubin can cross the blood brain barrier?
unconjugated bilirubin
What drug can cause hepatic jaundice?
acetominophen
What are the color of urine and feces in cholestatic jaundice?
dark urine and pale feces
Congenital erythropoietic porphyria is caused by a defeciency in what enzyme?
UPG III Synthetase
