Specialization of Proteins II

Question 1

Differentiate between reticulocytes and erythrocytes

Answer 1

Reticulocytes:

• precursors to RBCs
• contain no nucleus, but have some remaining ribosomes
• can’t replace degraded proteins
• represent about 1% of total RBC population
• in hemolytic anemia, the percentage of reticulocytes increases as they try to replace lost erythrocytes

Erythrocytes:

• mature RBCs
• contain no intracellular organelles
• shaped like biconcave discs
• transport oxygen and carbon dioxide between tissues and lungs
• by measuring RBC count in blood, can determine if a person is anemic, and along with other tests, what type of anemia and what may be causing it
• ex: iron deficiency can cause anemia because iron is a cofactor in Hb

Question 2

What is the role of carbohydrates associated with RBC membrane?

Answer 2

• located on surface of cell and are attached to either lipids or proteins (glycolipids or glycoproteins)
• these carbohydrates are important in cell to cell recognition (they are antigens)
• they also protect the lipids and proteins in the membrane from lipases and proteases (glycocalyx)

Question 3

What is the role of band 3 protein (anion exchange protein) associated with RBC membrane?

Answer 3

• the transmembrane protein that forms the channel for exchange of Cl- and HCO2- anions

Question 4

What is the role of cytoskeletal proteins associated with RBC membrane?

Answer 4

• interact to give RBC shape and flexibility
• spectrin is the primary protein, comprised of a pair of heterodimers
• spectrin binds to ankyrin, actin, and band 4.1 protein
• ankyrin binds to band 3, this interaction secures spectrin to the membrane
• actin binds to band 4.1, and band 4.1 interfaces with glycophorins in the membrane to help connect the cytoskeleton and the lipid bilayer

Question 5

Describe similarities and differences between myoglobin and hemoglobin

Answer 5

Both:

• are proteins that contain heme prosthetic groups and can bind to oxygen; oxygen will bind to a free electron on ferrous iron, Fe2+
• both have a crevice that forms an active site
• both composed mainly of alpha-helices (8) that fold to form the protein

Myoglobin:

• single globulin, therefore both histidines are exposed to the heme and play a role in active site
• located in muscle tissues
• transports oxygen
• much higher affinity for oxygen

Hemoglobin:

• located in blood
• transports oxygen
• tetrameric protein, with two alpha and two beta chains
• sigmoid curve for oxygen affinity

Question 6

Describe the alpha globin gene cluster

Answer 6

• has alpha 1 and alpha2 genes encoded, both are transcribed (duplicate genes)
• contains zeta gene

Question 7

Describe the beta globin gene cluster

Answer 7

• contains epsilon, Ggamma, Agamma (duplicate fetal genes), delta, and beta

Question 8

What is the globin chain composition of HbA1?

Answer 8

• two alpha polypeptides

- two beta polypeptides

Question 9

What is the globin chain composition of HbA2?

Answer 9

• two alpha polypeptides

- two delta polypeptides

Question 10

What is the globin chain composition of HbF?

Answer 10

• two alpha polypeptides

- two gamma polypeptides

Question 11

What are thalassemias?

Answer 11

• autosomal recessive
• both copies of the gene must be mutated for the disease to develop
• hereditary hemolytic disease caused by faulty hemoglobin synthesis

Question 12

What are the possible alpha thalassemias?

Answer 12

• there are four loci where mutation can occur: the allele for alpha1 and alpha2 on each chromosone
• no mutations: phenotype normal
• one loci mutated; biological effect is minimal; person is silent carrier
• two loci mutated; condition is known as alpha thalassemia minor (trait); mild microcytic, hypochromic anemia
• three loci mutated; alpha thalassemia intermidea, or HbH disease; both HbH (beta x4) or Hb Barts (gamma x4) can be present. Hb Barts occurs after birth due to only 25% normal alpha chains. Hb is unstable and has high oxygen affinity; poor oxygen delivery to tissues. Microcytic hypochromic anemia, and Heinz bodies (damaged precipitated Hb)
• four loci affected; fetus cannot survive; alpha thalaseemia major

Question 13

What are the possible Beta thalassemias?

Answer 13

• clinical presentation is more complicated due to possibility for beta gene to be deleted or have intermediate expression levels
• only two loci for mutation, one beta gene on each chromosone
• one beta gene mutated; beta thalassemia minor; mild microcytic anemia that is often asymptomatic
• both beta genes have intermediate expression levels; thalassemia intermedia; requires occasional transfusions
• both alleles mutated; thalassemia major (Cooley’s anemia); sever, microcytic, hypochromic anemia; transfusion-dependent
• alpha chain are unable to form a soluble tetramer; they accumulate and form precipitates, leading to hemolysis and anemia