Heme Degradation Flashcards
Heme catabolism
- lifetime of RBC-120 days
- 9 billion destroyed daily
- tracked radioactive glycine to figure out
removal of RBCs
- in spleen
- liver and bone marrow can
- reticular endothelial cells engulf through phagocytosis
hemoglobin break down
- globin is broken down to amino acids
- heme is broken down into iron which is recycled, and the rest of the ring is broken down and digeted
three steps to heme breakdown
- break the ring
- reduce the broken ring (both in reticular endothelial cells)
- conjugate to sugars to make it water soluble-in liver
haptoglobin
binds methemoglobin dimers (iron in ferric state)
in case of destruction away from spleen and liver
hemepexin
- binds free heme
- incase breakdown other than spleen and liver
transferrin
- binds free iron
- in case of destruction away from spleen or liver
hemolytic anemias
-10% of red cell destruction in plasma
heme degradation
- heme to biliverden (breaks ring and uses 02 and NADPH)
- biliverden to bilirubin
- conjugation of bilirubin
heme oxygenase
- heme to biliverden
- catalyzes the rupture of the methylidyne group of heme between the pyrrole rings carrying vinyl groups
- bridging carbon removed as CO
- 1% of hemoglobins binding sites have CO
- spleen, ER
bilirubin
- easily passes through PM b/c it is lipid soluble
- diffuses into bloodstream and binds with serum albumin and transported to liver
- major antioxidant
biliverden reductase
- uses NADPH
- biliverdento bilirubin
- in spleen
conjugation of bilirubin
- bilirubin-albumin into liver, transferred to bilirubin ligandin
- made water soluble by adding two UDP-glucaronic acids (from glycogen) to P side chains (one each)
- forms bilirubin diglucaronide (conjugated bilirubin) which is secreted in the bile
glucuronyl bilirubin transferase
-transfers two gluronic acids from UDP gluronic acid to the P side chains
Crigler-Najjir syndrome
-deficiency in UDP glucuronyl transferase-severe jaundice because bilirubin around
neonatal jaundice
- production of insufficient UDP glucuronyl transferase by the infant
- temporary
- phototherapy
- irradiated bilirubin breakdown products are more soluble than bilirubin and can be excreted by the liver into the bile without conjugation
conjugated bilirubin
- passes from liver into bile canaliculi, to gall bladder,to the GI tract
- bacteria convert it to urobilinogens and related products
- some urobilinogen reabsorbed into portal system, then re excreted into bile, some leaves via the kidney
- oxidation of urobilinogen leads to urobilin, which gives color to urine and feces
prehepatic jaundice
- massive breakdown of red blood cells resulting in overproduction of free bilirubin
- liver cells can’t conjugate bilirubin at the rate it enters the liver, get build up of unconjugated in blood
- sickle cell, MVA
- no conj bili, normal AST and ALT, normal ALP, no uring bilirubin, but there is urine urobilinogen
hepatic jaundice
- can’t conjugate or deposit
- diseased condition of the liver (hepatitis, cirrhosis), that prevents the uptake or conjugation of bilirubin
- both conj and unconj in blood
- high conj, high AST, ALT, normal ALP, has both urine bilirubin and urobilinogen
post-hepatic jaundice
- blockage of bile flow out of the liver and into the intestinal tract, build up of conj
- gal stones, pancreatic cancer
- high conj, normal AST/ALT, high ALP, urine bilirubin, no urine urobilinogen
iron storage
- ferritin and hemosiderin
- ferritin can contain 4500 atoms in a reversible manner
- hemosiderin is degraded form of ferritin
- increased in iron=increase in ferritin
- most reserve in liver, bone marrow, skeletal muscles, spleen
- can get iron tox in transfusion patients
transferrin
- takes Fe from spleen to marrow (RBCs take it the other way)
- glycoprotein synthesized in liver that it plasma localized
- protein and receptor recycled
- keeps serum levels low and is antimicrobial
absorption of iron by receptor mediated endocytosis
- ferro-transferrin binds receptor on cell membrane at pH 7
- receptor and ligand are taken up in clathrin coated pits
- pH in the vesicle is lowered to 5 which makes iron dissociate
- receptor and apotransferrin are returned to PM where pH is 7 and transferrin no longer binds
Fe3+ binds to transferrin well at pH 7
apotransferrin releases receptor at pH 7
