Red Blood Cell Metabolism

Question 1

Features of RBC that facilitate its function?

Answer 1

1. RBCs are biconcave shape so ↑ SA:V ratio, facilitating oxygen transport efficiently
2. RBCs have high elasticity & reversible deformable ability
3. Able to change its membrane shape & size when squeezing through narrow capillaries and regains its biconcave shape after without rupturing its membrane
4. RBCs obtain energy by anaerobic glycolysis

Question 2

Sites that HMP shunt is active

Answer 2

1. RBCs
2. Adipose tissue
3. Liver
4. Bone marrow

Question 3

How does the HMP shunt maintain RBC membrane integrity?

Answer 3

1. RBC membrane integrity is essential to maintain reversible deformable ability when passing through capillaries
2. RBCs are frequently exposed to highly oxidative environments so ↑ ROS is produced in metabolic reactions
3. ROS directly oxidizes macromolecules like polysaccharides, proteins & lipids
4. ROS are attractive to PUFAs in the cell membrane; they oxidize the PUFA & destroy phospholipids in the membrane
5. These accumulate in the membrane making it more rigid & damages membrane + impairs integrity
6. ROS also reacts with protein compounds in RBCs like Hb + oxidized -SH groups containing AAs get precipitated in RBC membrane
7. Further impairs integrity by producing Heinz bodies
8. NADPH acts as a reducing agent to maintain reduced glutathione levels in RBCs to prevent ROS damage to macromolecules
9. NADPH is exclusively produced in RBCs via the HMP shunt

Question 4

How does 2,3-BPG help RBC function?

Answer 4

1. 2,3 - Bisphosphoglycerate is produced by using intermediates of anaerobic glycolysis (takes place in RBC for ATP production)
2. 1,3 - BPG → 2,3 - BPG
3. RBCs transport oxygen from alveoli to tissue capillaries via blood (Hb is the main oxygen carrier)
4. 2,3 - BPG facilitates effective oxygen transport; it binds with Hb allosterically & tightens bonds b/w 2 dimers of Hb
5. Reduces oxygen affinity of Hb & stabilizes the T state
6. Shifts oxygen dissociation curve to the right
7. ↓ oxygen saturation at tissue level @ partial pressure of 40mmHg
8. 2,3 - BPG facilitates oxygen release towards tissue at tissue level for proper functioning of RBCs

Question 5

What are the mechanisms in RBC to prevent its lysis?

Answer 5

1. Antitrypsin is an alpha 1 - globulin plasma protein
2. Acts as carriers for lipids + hexosamines
3. Also acts as protease inhibitor (especially trypsin)
4. Trypsin produced by pancreas can be released into circulation due to pancreatic tissue damage or intestinal damage
5. So alpha 1 - antitrypsin inhibits trypsin and prevents conversion of trypsinogen → trypsin, hence it protects against tissue damage
6. In alpha 1 - antitrypsin deficiencies, the proteases that enter circulation cannot be inhibited
7. So cannot prevent the conversion
8. These proteases will hydrolyse protein compounds in tissues
9. Leads to tissue damage