Hemoglobin Flashcards
How many red blood cells are produced per second?
2.4 million RBC/s
How long do red blood cells last?
120 days
What is the function of erythrocytes?
To transport oxygen from the lungs to the tissue.
How man liters of O₂ per day do human red blood cells carry?
500-1,000 liters
What percent volume of the erythrocyte does hemoglobin occupy?
33%
What percent of hemoglobin is synthesized before extrusion of the nucleus?
65%
Reticulocytes make what remaining percent of Hb?
35%
What percent of protein synthesis in reticulocytes is globin synthesis?
95%
Explain the stages of erythropoiesis, what happens at each phase, and what cell types are present?
Stem cell: (Hemocytoblast)
Commited cell: (Proerythroblast)
Phase 1: “ribosome synthesis” (Early erythroblast, Late erythroblast)
Phase 2: “Hb accumulation” (Late erythroblast, Normoblast)
Phase 3: “nucleus ejection” (Normoblast, Reticulocyte)
: Erythrocyte
What part of the body makes red blood cells at each point of development?
0-8 wks: Yolk sac
1 mos-birth: Liver
2 mos-birth+2 mos: Spleen
7 mos+: Bone marrow
What are the hemoglobin levels by age and sex?
Adult male: 14-18 g/dL
Adult female: 12-16 g/dL
Newborn: 111-16 g/dL
Child: 12-15 g/dL
What is the subunit protein structure of hemoglobin?
Tetramer
What is the globin stuctrue of hemoglobin?
2 ∝-globin chains
2 β-globin chains
How many heme per subunit and what is the charge of the iron atom?
1 heme per subunit
ferrous iron, Fe²⁺
What kind and how many rings are in the hemoglobin structure?
4 protoporphyrin IX rings
What are the types of globin chains in a normal adult?
∝ (alpha)
β (beta)
𝛿 (delta)
γ (gamma)
What is the length of the globin chains?
∝ globin= 141 amino acids
all others= 146 amino acids
Which chains are ∝-like?
ζ (zeta)
∝ (alpha)
Which chains are β-like?
ε (epsilon)
γ (gamma)
𝛿 (delta)
β (beta)
What are the globin genes?
HBA1, HBA2, HBB
What are the homoglobin names?
HbA, HbS, HbSC, HbF, Gower, Portland
Where are the globin genes located?
β globin genes= Chromosome 11
∝ globin genes= Chromosome 16
When is embryonic hemoglobin expressed and where is it made?
Yolk sac from 0-8 wks
When is fetal hemoglobin primarily expressed and where is it predominately made?
Liver & bone marrow from 34-36 wks
What does hemoglobin switching depend on?
Gestational age (time of fertilization)
What percentage of each hemoglobin type is present in a normal adult?
HbA: 97%
HbA2: 3%
HbF: 0.5%
What are the different types of hemoglobin and what globin chains are they made of?
Adult: *HbA (∝2β2) *HbA2 (∝2𝛿2) Fetal: *HbF (∝2γ2) Embryonic: *Hb Gower 1 (ζ2ε2) *Hb Gower 2 (∝2ε2) *Hb Portland (ε2γ2) Sickle cell: *HbS
What substitution occurs to cause sickle cell anemia and at what position does it occur?
An amino acid at position #6 in β globin substitutes valine for glutamic acid.
What causes the sickle shape shape in sickle cell anemia?
Polymerization of hemoglobin forming rods?
What are symptoms associated with sickle cell anemia?
Impeded circulation, hemolytic anemia, pain, organ damage strokes increased infections
What is a treatment for sickle cell anemia and what is the drawback?
Treatment with hydroxyurea to induce HbF & address inflammation. It is a chemotherapeutic agent.that can cause cancer.
In what order are globin genes arranged on the chromosome?
Linearly 5’ to 3’ in the same order of activation as expression.
What is the prosthetic group of hemoglobin?
Heme, a non-amino acid group
What is the organic component of heme and how many pyrole rings does it have?
Protoporphyrin
4 pyrole rings
How are amino acids labeled in hemoglobin?
Names according to helical segment & # amino acid in that segment e.g. F8 & E7
Which amino acid is bound to the heme group?
F8 the proximal histidine
Which amino acid is bound to the iron that O₂ binds to along with heme?
E7 the distal histidine
What stabilizes O₂ binding to iron?
E7 forming a H-bond with O₂
What occurs after O₂ binds iron?
A 0.4 Å shift pulls the rest of the globin chain pulling the F8 histidine
What is the structure of myoglobin?
Monomer
Where and at what pressure does hemoglobin pick up O₂ and where and at what pressure does hemoglobin drop off O₂?
Picks up O₂ in the lungs @ 100 mm Hg and drops it off to myoglobin in the tissues @ 10-20 mm Hg
What does it mean that O₂ binds cooperatively and what kind of curve represents this?
1 O₂ binding causes conformational ∆ in ∝-helix which ↑ affinity to bind more O₂. Represented by sigmoidal curve
What modulates Hb function and how does it change O₂ affinity?
↑ 2,3-BPG= ↑T form= ↓ O₂ affinity
↓ pH= ↓O₂ affinity
R form= ↑O₂ affinity
What is the sequential model?
Hb binds/releases O₂ sequentially
What is the concerted model?
Hb binds/releases O₂ all at once
What is carboxyhemoglobin and how strongly does it bond O₂?
CO+heme→carboxyhemoglobin, CO bond= 210* O₂ bond
What is HbA1c? What is its normal level and diabetic level?
β-globin+glucose→ HbA1c= irreversible.
Normal level= 3%= 2-3 in diabetics
