Hematopoiesis: erythrocytes

RBC: Spectrin & Glycophorin

• Spectrin:

  • Peripheral membrane protein

  • Intertwined alpha and beta chains→ forms flexible tetramers

  • Forms microfilament skeletal structure

  • Connects RBC skeleton network together, stabilizes junction between spectrin and actin

• Glycophorin

  • Integral membrane/ transmembrane protein

  • Negative charge (sialic acid)→ RBCs repel each other

  • Interacts with outside antigens and transports them inside

  • Cytoskeleton allows cell support, stability, flexibility, deformability

  • Anchors inner spectrin skeleton to outer lipid membrane

  • Glygophorin A (GPA) most common, but there’s A-E variants

RBC: Actin and Ankyrin

• Actin

  • Junctional complex between spectrin tetramers

  • Links integral membrane proteins (like band 3) via proteins like ankyrin and protein 4.1

• Ankyrin

  • Links integral membrane proteins to spectrin-actin cell cytoskeleton intracellularly

  • Cluster and positions ion channels, ion exchangers, transporters, cell-adhesion molecules to specialized membrane domains

  • Have 33-AA repeats

RBC: Band 3, Band 4.1

• Band 3

  • Ion exchange: Trades chlorine for bicarbonate (HCO₃⁻) across membrane→ CO2 transport

  • Structural supprot: connects outer lipid payer to internal skeleton tia ankyrin

• Band 4.1

  • Links inner skeleton proteins to outer membrane proteins (ex: GPC and band 3)

  • General structural and flexible support

RBC ions

Maintained by Na+/K+ -ATPase (sodium potassium pump)

• Transports 3 Na+ outside, and 2 K+ inside

• Failure= Na+ enters, K+ leaves cell→ Lysis

Na+ higher on outside, K+ higher on inside

• High extracellular K+ could also be caused by hemolysis after centrifugation

Hemolytic anemia: Lysis of RBCs

RBC metabolism- ATP

No nucleus= no oxidative respiration to metabolize glucose and obtain ATP

RBCs use glycolysis via Embden-Meyerhof pathway (EMP) (mnemonic: MeyeRBC)

• Glucose→ Absorbed through plasma membrane→ metabolizes to lactic acid (instead of pyruvic acid)→ 2 ATP per glucose

• Goes through aerobic phosphorylation and anaerobic glycolysis

RBC metabolism- oxygen

Via Luebering-Rapport shunt (mnemonic: Wrapper like wrapping up oxygen)

Produces 2,3-DPG or BPG (2,3 DIphosphoglycerate)

• Presence= Closed salt bridge→ Prevents Hgb to grab O2 (tense state)

• Absence= open salt bridge→ Delivery of O2 to tissues. Offloads 25%

Oxygen dissociation curve

Sigmoid curve

Bohr effect: Hgb’s O2 binding affinity inversely related to acidity and concentration of carbon dioxide

In lungs (pressure is 100 mm Hg), Hgb fully saturated: has all O2 it can hold.

At 40 mm, Hgb saturated 50% but willing to give up 50% of it’s O2

normal blood: pH 7.4. 75% Hb has O2, 25% can be released to tissues

Right shift: lower pH (7.2), Increased 2,3 DPG, higher body temperature, more CO2→ more Oxygen offloaded

RBC metabolism- glutathione

Via Pentose Phosphate Pathway (PPP)