5: RBC Biochem Flashcards
Lifespan of an RBC
120 days
During what stage of erythropoiesis is the majority of Hb synthesized?
Before nulceus is extruded to form a reticulocyte from a normoblast
HbF composition
A 2 y 2
Two types of adult Hb composition
HbA: a 2 B 2
HbA2: a 2 D 2 (only 3%)
Iron positioning in heme before vs after O2 binds
Before: Fe slightly outside plane of porphyrin
After: moves into plane -> pulling down proximal histidine -> changes interactions with associated globin chains
Type of oxygen dissociation curve for hemoglobin vs myoglobin
Hemoglobin: sigmoid also (due to cooperativity)
Myoglobin: hyperbolic
Cooperative binding of Hb
Binding one molecule of O2 facilitates binding of another by pulling the proximal histidine downward
Partial pressure of O2 in the lungs
About 100 mmHg
Why is Fe an ideal catalyst for redox reactions
It readily exchanges electrons
Two states of iron
Ferrous: Fe2+
Ferric: Fe3+
Two major functions of Fe
- Oxygen transport via Hb
2. Component of cytochromes in ETC
Main way iron is regulated
Modulating absorption
Two major places iron is found in the body
- Hb: 67%
2. Stored iron as ferritin: 27%
What product is formed during ferritin breakdown
Hemosiderin
Main source of heme vs non-Heme iron
Heme: animal products on-heme: plant products
What does ferric reductase require to function?
Vitamin C
What does ferroportin require vs what regulates it?
Requires hephaestin, blocked by hepcidin
What happens when hepcidin binds ferroportin?
Internalization of ferroportin + degradation in lysosomes
Three things that control levels of hepcidin
- Transferrin
- Transferrin receptor
- HFE: human homeostatic iron regulator protein
Hepcidin expression when iron is high vs low
High iron: high hepcidin
Low iron: low hepcidin
Causes of iron deficiency
- Insufficient dietary iron or absorption
- Excess blood loss
- Overuse of aspirin
- Ulcers of GI tract
What type of anemia occurs from iron deficiency
Hypochromic microcytic anemia
Two compounds necessary for RBC production
Folate, vitamin B12
Why does a deficiency in vitamin B12 or folate cause anemia?
Diminished DNA synthesis
Where is folic acid found in diet?
Most foods - fruits, liver, eggs, milk, legumes, yeast, and especially leafy veggies
How much folate is stored in the liver?
5-10 mg, which can last 3-6 months
Methotrexate
Inhibits FH2 reductase -> antineoplastic agent
85% of B12 deficiency is due to what?
Lack of intrinsic factor
Test to determine cause of pernicious anemia
Schilling test
Describe part one of schilling test
- Given Cobalt-labeled B12 + unlabeled B12 -> saturates receptors in liver so that if absorbed, will pass into urine
- Urine collected for 24 hours
- If radioactivity is present -> normal
- If radioactivity NOT present -> pernicious anemia -> move to part 2
Describe part 2 of the schilling test
- Give dose of cobalt-labeled B12 + intrinsic factor + some unlabeled B12 to saturate the receptors
- Urine collected for 24 hours
- If radioactive B12 present -> pernicious anemia due to lack of intrinsic factor
How many globular units comprise hemoglobin
Four
Describe a Porphyrin ring
Four 5-membered rings containing N connected by single carbon bridges
Two locations of heme biosynthesis
Liver, erythroid cells of bone marrow
What occurs with defects in heme synthesis?
Porphyrias
Major antagonist of ALA synthase
Heme
Two enzymes inactivated by Lead, especially in lead poisoning
- ALA dehydratase
2. Ferrochelatase
Lead poisoning - what accumulates and what is causes
ALA accumulates -> is neuro toxic -> neuro sx and anemia and energy metabolism is impacted
Porphyria
Genetic disorder caused by defects in heme synthesis
Acute hepatic vs erythropoietin porphyrias in general
Acute hepatic: neuro sx
Erythropoietin: skin sx, photosensitivity
What does porphyria mean in Greek?
Purple pigment
Which type of bilirubin is insoluble?
Unconjugated/indirect
What is added to bilirubin to make it conjugated?
Glucuronic acid
How does phototherapy work for jaundice?
Blue fluorescent light causes BR to undergo conversion into a more soluble isomer
