Pyruvate Kinase Deficiency in Red Blood Cells

• RBCs don't have mitochondria

• They rely on anaerobic glycolysis for energy

  • no TCA or ETC

1. Pyruvate Kinase Deficiency ➡️

2. Slow Glycolysis ➡️

3. Loss of ATP ➡️

4. Can't Power/Run Sodium-Potasium-ATPase ( pump ) ➡️

5. Sodium ions accumulate in cytosol ➡️

6. Osmotic pressure increases ➡️

   • cell looses shape here , becomes "spiculated"

7. Cell lyses ➡️

8. Anemia

9. Build up of 2,3-BPG

Major Protein Kinase Families

• Serine / Threonine

  • example = AMPK

• Tyrosine

  • example = insulin receptor

• Serine / Threonine and Tyrosine ( dual-specificity )

  • can phosphorylate both serine/threonine and tyrosine residues

  • example = MEK1 / MEK2 ( Mitogen-Activated Protein Kinase Kinase )

• Histidine

  • example = CheA ( involved in bacterial chemotaxis )

Know 3 Receptors that Act via Tyrosine Kinase Signaling

• RTKs are generally membrane-anchored to facilitate ligand binding and signal transduction

1. Insulin

   • stimulates carbohydrate utilization and protein synthesis

   • rate = seconds to minutes

     • direct ligand to receptor binding

     • immediate release of pre-stored granules

     • but also has longer transcriptional effects

2. Platelet Derived Growth Factor

   • stimulates survival , growth , proliferation , and migration of various cell types

   • rate = minutes to hours

     • needs time for secondary signaling cascades to occur

3. Nerve Growth Factor

   • stimulates survival and growth of some neurons

   • rate = hours to days

     • transcriptional changes take a while

Major Protein Phosphatase Families

• unlikely to be on the quiz

1. Protein Phosphateses

   • remove phosphate groups from proteins, reversing the action of kinases to regulate cellular processes like metabolism, signaling, and cell cycle.

2. Nucleotidases

   • hydrolyze phosphate groups from nucleotides ( e.g., AMP, ADP, ATP ) to maintain nucleotide balance and regulate energy metabolism.

3. Gluconeogenosis

   • enzymes like glucose-6-phosphatase and fructose-1,6-bisphosphatase that dephosphorylate metabolic intermediates in the gluconeogenesis pathway to produce glucose from non-carbohydrate precursors