Glycolysis - Biochemistry - Medbullets Step 1

Overview
- Function
  - generation of ATP from glucose via substrate-level phosphorylation (as opposed to oxidative phosphorylation)
    
    used by all cells
    
    with O₂
    
    pyruvate enters citric acid cycle (after being created in glycolysis)
    
    NAD+ regenerated via oxidative phosphorylation
    
    without O₂
    
    pyruvate cannot enter citric acid cycle after glycolysis
    
    NAD+ must be regenerated via conversion of pyruvate to lactate
    
    catalyzed by lactate dehydrogenase
    
    only source of energy for RBCs
  - generation of intermediates for other pathways
    
    1,3-BPG
    
    intermediate of glycolysis
    
    can be converted to 2,3-DPG
    
    modifies the hemoglobin-O₂ binding curve
    
    binds HbA and ↓ binding affinity of O₂
    
    a compensatory mechanism for ↓pO₂
- Pathway
  - in cytoplasm
  - irreversible
  - net reaction
    
    glucose + 2P_i + 2 ADP + 2 NAD⁺ → 2 pyruvate + 2 ATP + 2 NADH + 2H⁺ + 2 H₂O
- Important enzymes
  - hexokinase - converts glucose into glucose-6-phosphate allowing "trapping" inside cell
    
    distribution
    
    widely present in most body tissues
    
    allows trapping of glucose at all blood glucose levels
    
    kinetics
    
    high affinity → low K_m
    
    low capacity → low V_max
    
    regulation
    
    feedback inhibited by glucose-6-phosphate
  - glucokinase (hexokinase IV)
    
    distribution
    
    liver
    
    β cells of pancreas
    
    uses as a means to measure blood glucose and release insulin accordingly
    
    mutated in the monogenenic, autosomal dominant form of diabetes called Maturity Onset Diabetes of the Young type 2 (MODY2)
    
    kinetics
    
    low affinity → high K_m
    
    high capacity → high V_max
    
    regulation
    
    induced by insulin (to store glucose in liver after a meal)
    
    no direct feedback inhibition
  - phosphofructokinase-1
    
    rate-limiting step
    
    inhibited by ATP, citrate
    
    stimulated by AMP, fructose-2,6-bisphosphate
    
    fructose 2,6-bisphosphate synthesized by phosphofructokinase-2
  - pyruvate kinase
    
    catalyzes substrate-level phosphorylation
    
    inhibited by ATP, alanine
    
    activated by fructose-1,6-bisphosphate
- Hormonal regulation
  - fasting state
    
    ↑ glucagon → ↑ cAMP → ↑ protein kinase A → ↑ FBPase-2, ↓ PFK-2
  - fed state
    
    ↑ insulin → ↓ cAMP → ↓ protein kinase A → ↓ FBPase-2, ↑ PFK-2

Disorders of Glycolysis
- Pyruvate kinase deficiency
  - AR (most commonly)
  - pathophysiology
    
    ↓ ATP generation
    
    inability to maintain Na+/K+ ATPase leads to
    
    RBC swelling
    
    RBC lysis
    
    back up of glycolysis
    
    ↑ 2,3-BPG and other glycolytic intermediates
  - presentation
    
    chronic hemolysis
    
    ↓ O₂ affinity for HbA
    
    due to ↑ 2,3-BPG
    
    no Heinz bodies
    
    unlike glucose 6-phosphate dehydrogenase deficiency

Action	Numeric Key	Letter Key	Function Key
Show Bullets		S	Enter (frontside only)
20%	1	N
40%	2	H
60%	3	F	Enter (backside only)
80%	4	E
100%	5	M
Toss	0	T