Glycolysis Lecture Notes 🧬

Overview

• Topic: Glycolysis
• Importance: First step of carbohydrate metabolism to derive energy (ATP) from glucose
• Summary: Glycolysis, link reaction, Krebs cycle, and finally ATP generation
• Focus: Detailed discussion on only glycolysis

Glycolysis Background

• Carbohydrates: Monosaccharides (e.g., glucose - hexose sugar, 6-carbon compound)
• Objective: Convert glucose to ATP through various cycles
  • Glycolysis
  • Link reaction (Pyruvate Dehydrogenase Cycle)
  • Krebs Cycle
• Types: Aerobic vs. Anaerobic Glycolysis

Aerobic Glycolysis

• Occurs in the presence of mitochondria and oxygen
• End product: Pyruvate

Anaerobic Glycolysis

• Occurs in absence of mitochondria or oxygen (e.g., in RBCs, exercising muscles)
• End product: Lactate

Glucose Transporters (GLUTs)

• Function: Transport glucose from blood to cells
• **Types: Sodium-Dependent and Glucose Transporters (GLUTs) **

Sodium-Dependent Glucose Co-Transporters (SGLT)

• SGLT-1: Present in proximal tubule of kidney & luminal side of intestine
• SGLT-2: Present in proximal tubule of kidney
• Transport Mechanism: Against concentration gradient, use ATP generated elsewhere

GLUTs

• Insulin-Independent: GLUT-1, GLUT-2, GLUT-3, GLUT-5
• Insulin-Dependent: GLUT-4

Key GLUT Locations

• GLUT-1: RBCs, retina, brain, kidney, placenta, colon
• GLUT-2: Beta cells of the pancreas, liver, basolateral surface of the intestine, proximal convoluted tubule of kidney
• GLUT-3: Brain, kidney, placenta
• GLUT-4: Heart, skeletal muscle, adipose tissue
• GLUT-5: Luminal side of small intestine and spermatozoa (transports fructose)

Detailed Glycolysis Pathway (EMP Pathway)

• Definition: Sequence of reactions converting glucose to pyruvate with ATP production
• Location: Cytoplasm of the cell
• Phases: Preparatory phase, Splitting phase, Payoff phase

Phases Breakdown

1. Preparatory Phase

   • Convert glucose to glucose-6-phosphate (enzyme: hexokinase/glucokinase)
   • Conversion to fructose-6-phosphate then to fructose-1,6-bisphosphate (enzyme: phosphofructokinase)

2. Splitting Phase

   • Split fructose-1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (enzyme: aldolase)
   • Interconversion of DHAP and glyceraldehyde-3-phosphate (enzyme: triose phosphate isomerase)

3. Payoff Phase

   • Convert glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate (enzyme: glyceraldehyde-3-phosphate dehydrogenase)
   • Convert 1,3-bisphosphoglycerate to 3-phosphoglycerate (enzyme: phosphoglycerate kinase)
   • Convert 3-phosphoglycerate to 2-phosphoglycerate (enzyme: phosphoglycerate mutase)
   • Convert 2-phosphoglycerate to phosphoenolpyruvate (enzyme: enolase)
   • Convert phosphoenolpyruvate to pyruvate (enzyme: pyruvate kinase)

Hexokinase vs. Glucokinase

• Hexokinase: Active in low glucose, found in extra-hepatic tissues, feedback-inhibited by glucose-6-phosphate
• Glucokinase: Active in high glucose, found in liver and pancreas, induced by insulin

Anaerobic Glycolysis

• Steps: Similar to aerobic but pyruvate converts to lactate (enzyme: lactate dehydrogenase)
• Conditions: Lack of mitochondria or oxygen

Energetics

Aerobic Glycolysis

• Preparatory Phase: -2 ATP
• Payoff Phase: +4 ATP, +2 NADH (total: 7 ATP net gain)

Anaerobic Glycolysis

• Preparatory Phase: -2 ATP
• Payoff Phase: +4 ATP (total: 2 ATP net gain)

Total ATP Yield (Aerobic Oxidation of Glucose)

• Summary: Glycolysis (7 ATP) + Link reaction (5 ATP) + TCA cycle (20 ATP) = 32 ATP

Regulation and Inhibition

Regulatory Enzymes

• Hexokinase/Glucokinase
• Phosphofructokinase-1: Key regulator
• Pyruvate Kinase

Inhibitors

• Arsenate and Iodoacetate: Inhibit glyceraldehyde-3-phosphate dehydrogenase
• Fluoride: Inhibits enolase

Additional Pathways

Rapoport-Luebering Shunt

• Significance: 2,3-BPG production, which aids in oxygen release in hypoxia
• Overall ATP Gain: No net ATP in RBCs through this shunt

Summary

• Thorough breakdown of glycolysis, including glucose transporters, key steps, regulations, energetic outcomes, and lecture keynotes.