Flashcards in Lecture 38 Deck (21):
What is present to shuttle Iron into the cell? What oxidation state can it be in? Is it complete absorption?
- active transport system
- +2 or +3
- no - iron absoprtion isn't very efficient
What are some iron transporters and how much iron do they carry?
Ferritin (4500 Fe), Transferrin (2 Fe), Lactoferrin (to get iron into milk)
How much iron is in a 70 kg human? Where is it mainly?
- 3-4 g
- hemoglobin or stored ferritin in liver, reticuloendothelial cells and muscle
What convert Fe+2 to Fe+3? Why is this important?
- in order for RBCs to carry O2, Fe must be +2
What is iron deficiency anemia?
- Poorly developed RBCs when FE not available for Hgb synthesis
What is Hemochromatosis?
- Excessive Fe absorption and storage leads to liver and other tissue damage
What is a heme? Where does synthesis occur?
- A porphyrin ring with Fe
- Synthesis occurs in all tissues, enriched in marrow and liver
Heme synthesis begins and ends in what compartment? Where do the intermediate steps occur?
What two compounds combine in the first step of Heme synthesis? What is the enzyme? What inhibits it? What is the cofactor?
- succinyl CoA and glycine
- ALA synthase
- Pyridoxal phosphate (a b vitamin)
What is the general name for the intermediates occurring in the cytosol during heme synthesis?
How does the ALA synthase get into the mitochondria? What inhibits transcription of this enzyme?
- a basic signalling sequence is present at its end, a chaperone protein and ATP attach and it gets shuttled in
What happens when 3 H2 are removed from Protoporphyrinogen IX to make Protoporphyrin IX (porphorinogens)?
- more double bonds - double bond structure changes
What is a derangement in a number of genes or poryphyrin synthesis called that occur in a number of species called? Dominant or recessive? What happens in case of dominant? What can happen? What do they primarily affect? Where does most heme synthesis occur?
- can be both
- gain of function and overproduction of intermediates
- Defective Hgb and other heme-protein synthesis
- buildup of precursors to blockage point (reddish, brownish, light sensitive)
- nervous system, skin, liver, blood
What does auto-oxidation of Fe2+ in hemoglobin to Fe3+ produce? What color is triple state? What enzyme returns to 2+ state? What is needed for this reaction?
- inactive methemoglobin and superoxide
- methemoglobin reductase (MR)
Where is hemoglobin catabolized? What happens to the protein (globin)? What happens to the AA? What happens to Heme?
- reticuloendothelial (RE) cells of spleen and bone marrow
- cleaved off, hydrolyzed, exported as AA
- reused by organism
- degraded and must be excreted (3-5 mg/kg/day)
What breaks open Heme ring structure and removes Fe3+? What does it use? What is made? What converts Biliverdin to bilirubin? what does it use? What color is biliverdin? Bilirubin?
- heme oxygenase
- Biliverdin IXa
- biliverdin reductase
Bilirubin still isn't that soluble - how does body make it so? What enzyme does this? Where primarily? Why is this good?
- glucuronate conjugation
- Bilirubin UDP glucuronyltransferase
- bilirubin can be excreted via the bile ducts > gi tract > fisces
Where does liver take up bilirubin from? Where does it move it? What does it do with it there?
- smooth ER
- conjugates it, excretes into bile
Most of bilirubin is excreted as what? What percentage ends up in periperal blood? What percentage is sent back to liver?
Can disorders be measured using conjugated and unconjugated bilirubin in blood? What does elevated conjugated bilirubin mean? Elevated unconjugated?
- problem in excretion
- problem in transport or conjugation in the liver