Review 10: Heme Metabolism Flashcards
Where is the biggest site of heme biosynthesis in the body?
1) bone marrow (for incorporation into hemoglobin)
2) liver (incorporation into cytochromes)
Define porphyria
genetic diseases resulting from abnormalities of enzymes of heme biosynthesis
Catabolism of heme produces ____________
bilirubin
What organ takes up bilirubin, conjugates it, and secretes it into bile?
the liver
What is the rate limiting step in heme biosynthesis?
Step 1 (succinyl coA + glycine ——> ALA) occurs in the mitochondria
Where in the cell does heme biosynthesis occur?
Steps 1, 6, 7, 8 –> mitochondria
Steps 2, 3, 4, 5 –> cytosol
What is the defining characteristic of porphyrinogen?
NO double bonds at bridging carbons (colorless)
What is the defining characteristics or porphyrins?
double bonds at bridging carbons (COLORED)
True or false: there is only one ALA synthase for both the liver and the bone marrow
FALSE (different enzymes under different regulation)
Which ALA synthase is regulated by heme?
ALAS1 in the liver
What is responsible for causing symptoms in porphyrias?
increase in metabolic intermediates (not a decrease in heme production)
What are 2 types of porphyria?
1) acute intermittent (deficiency of porphobilinogen deaminase leading to a build up of porphobilinogen)
2) variegate (cutaneous) (deficiency of
both have reduced heme synthesis
What does lead poisoning do to the body?
inhibit 3 important enzymes in the heme biosynthetic pathway
What is half life of RBCs?
120 days
Unconjugated bilirubin is carried in the plasma as a complex with _________
albumin (delivered to the liver)
How is unconjugated bilirubin conjugated in the liver?
2 glucuronic acid groups (from UDP-glucuronate) are attached to unconjugated bilirubin via propionic acid side chains
Where is bilirubin diglucuronide deconjugated?
the intestine by bacterial flora
oxidized to stercobilins which give stool its color
What compound gives urine its color?
urobilin
What is the cut off for classifying hyperbilirubinemia?
> 1mg/dL
True or False: hyperbilirubinemia only counts the conjugated form
FALSE; can be either the conjugated or unconjugated form
What is responsible for the yellowing color in jaundice?
elevated bilirubin diffusing into tissues (detectable in sclera when bilirubin reaches 2-2.5mg/dL)
Why is hyperbilirubinemia dangerous?
Conjugated form: benign
Unconjugated form: benign when bound to albumin (<25mg/dL) but above that when it is free, it can enter the brain and cause toxic encephalopathy
What are some causes of jaundice?
1) Hemolysis (increase in unconjugated bilirubin)
2) Biliary obstruction (conjugated spills over into blood – dark urine and chalky white feces)
3) hepatitis/cirrhosis (decreased conjugation of bilirubin)
4) Neonatal physiological jaundice – immature hepatic system (increase in unconjugated bilirubin)
Why are jaundice babies treated with UV light?
blue light can convert the insoluble, BBB permeable unconjugated bilirubin into isomers that are more soluble
