Flashcards in Lecture 38 Deck (21):
1
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
2
What are some iron transporters and how much iron do they carry?
Ferritin (4500 Fe), Transferrin (2 Fe), Lactoferrin (to get iron into milk)
3
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
4
What convert Fe+2 to Fe+3? Why is this important?
- ferroxidases
- in order for RBCs to carry O2, Fe must be +2
5
What is iron deficiency anemia?
- Poorly developed RBCs when FE not available for Hgb synthesis
6
What is Hemochromatosis?
- Excessive Fe absorption and storage leads to liver and other tissue damage
7
What is a heme? Where does synthesis occur?
- A porphyrin ring with Fe
- Synthesis occurs in all tissues, enriched in marrow and liver
8
Heme synthesis begins and ends in what compartment? Where do the intermediate steps occur?
- mitochondria
- cytosol
9
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
- Heme
- Pyridoxal phosphate (a b vitamin)
10
What is the general name for the intermediates occurring in the cytosol during heme synthesis?
- porphorinogen
11
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
- heme
12
What happens when 3 H2 are removed from Protoporphyrinogen IX to make Protoporphyrin IX (porphorinogens)?
- more double bonds - double bond structure changes
13
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?
- porphryias
- 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
- liver
14
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
- brown
- methemoglobin reductase (MR)
- NADH
15
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)
16
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
- NADPH
- Biliverdin IXa
- biliverdin reductase
- NADPH
- blue-green
- yellow
17
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
- liver
- bilirubin can be excreted via the bile ducts > gi tract > fisces
18
Where does liver take up bilirubin from? Where does it move it? What does it do with it there?
- blood
- smooth ER
- conjugates it, excretes into bile
19
Most of bilirubin is excreted as what? What percentage ends up in periperal blood? What percentage is sent back to liver?
- urobilinogen
- 15%
- 14%
20
Can disorders be measured using conjugated and unconjugated bilirubin in blood? What does elevated conjugated bilirubin mean? Elevated unconjugated?
- yes
- problem in excretion
- problem in transport or conjugation in the liver
21