Structure and function of hemoglobin Flashcards
What are the main components of HbA?
2-alpha chains
2-beta chains
Heme
What are the main components of HbA2
2-alpha chains
2-sigma chains
Heme
What are the main components of HbF?
2 alpha chains
2 gamma chains
Heme
What are the main components of HbA1c?
2 alpha chains
2 beta chains
Glucose
What is the attachment point of the glucose on HbA1c?
Amino group of the N-terminal valine of the beta-globin chain
What chromosome carries the alpha-globin genes?
Chromosome 16
What chromosome carries the beta-globin genes?
Chromosome 11
What are the embryonic hemoglobins?
Hb Gower 1
Hb Gower 2
Hb Portland
What, located upstream of the beta-globin genes, plays a significant role in expression?
Locus control region
What are the components of heme?
Ferrous iron - Fe++
Protoporphyrin IX
What are the 6 bonds to the ferrous iron in heme?
4 to the nitrogens in the porphyrin ring
1 to the histidine of globin
1 left available to bind to O2
How many heme are in each hemoglobin?
4
What is the function of the distal histidine in the heme binding site?
Stabilizes O2 binding to Fe++
What is the T form of Hgb?
Deoxygenated form with a low affinity for oxygen
What is the R form of Hgb?
Oxygenated form with high O2 affinity
What is the purpose of cooperative binding?
Allows Hgb to deliver more O2 to tissues
What is the function of myoglobin?
Reservoir of oxygen and as an oxygen carrier in muscle cells
What is the shape of the oxygen dissociation curve for myoglobin?
Hyperbolic
What is the shape of the oxygen dissociation curve for hemoglobin and why?
Sigmoidal because of cooperative binding
What factors affect the unloading and loading of O2 to hemoglobin?
PO2
pH
PCO2
Concentration of 2,3-BPG
What is the influence of low pH and increased PCO2 on the oxygen dissociation curve?
Increased unloading, shift curve to the right
What will happen to the oxygen dissociation curve if Hgb has a higher affinity for oxygen?
It shifts to the left
What is the function of 2,3-BPG and when is its concentration higher?
Decreases oxygens affinity for Hgb
Hypoxia and anemia
What occurs to the oxygen dissociation curve in chronic anemia?
Curve shifts to right –> increased O2 disassociation
What occurs to the oxygen dissociation curve during a panic attack?
Curve shift to the left –> hypoventilation decreased PCO2
What occurs to the oxygen dissociation curve in hypothermia?
Shifts to the left
What component performs the buffering action of Hb?
Imidazole group of histidine residues binds H+
What is the defect in HbS?
Glutamic acid at 6th position of beta-globin chain is replaced by valine
What is the defect in HbC?
Glutamic acid in the 6th position of beta-globin is replaced by lysine
What is the defect in HbSC?
Both HbS and HbC present
What is defect in thalessemia?
Imbalance in the synthesis of globin chains
What is the defect in methemoglobinemias/HbM)
Oxidation of heme iron from ferrous to ferric (Fe++ to Fe+++)
Is HbM/metHb able to bind oxygen?
No
What characterizes HbM?
Chocolate cyanosis –> brown colored blood with cyanosis
What enzyme may be deficient in HbM?
NADH-metHb reductase
What is the treatment for metHb?
Methylene blue
What can cause acquired metHb?
nitrate drugs
What changes to the oxygen dissociation curve are seen with CO?
Shifts curve to the left
Lowers plateau
Becomes hyperbolic