Glycolysis

The Embden-Meyerhof Pathway

I. Key Overview

A. Glycolysis1. Essential pathway for breaking down glucose2. Produces energy in the form of ATP3. Converts glucose into pyruvate4. Pyruvate generates Acetyl CoA for the Krebs cycle

II. Previous Concepts in Cellular Metabolism

A. Formation of Acetyl CoA1. Occurs through oxidation of substrates including pyruvate2. Involves oxidation-reduction reactions generating electron carriers (NADH, FADH2)

III. Importance of Glucose

A. Central Role in Metabolism1. Primary fuel source for brain and tissues2. Regulation of glucose levels impacts obesity and diabetesB. Metabolic Pathways Related to Glucose1. Links to glycogenolysis, gluconeogenesis, lactate production, and Krebs cycle

IV. Glycolysis - Summary of Stages

A. Overview of Glycolysis1. Occurs in cytoplasm2. Divided into two phasesa. Investment Phaseb. Energy Capture PhaseB. Stages of Glycolysis1. Stage 1: Priming of Glucosea. Requires 2 ATP to convert glucose to fructose 1,6-bisphosphate2. Stage 2: Splitting the Intermediatea. Fructose 1,6-bisphosphate splits into G3P and DHAP3. Stage 3: Oxidoreduction-Phosphorylationa. Produces ATP and NADH through substrate-level phosphorylation to pyruvate

V. Key Enzymes and Steps in Glycolysis

A. Step 1: Hexokinase Reaction1. Phosphorylates glucose to form glucose 6-phosphate2. Irreversible to retain glucose for metabolismB. Step 2: Isomerization1. Converts glucose 6-phosphate to fructose 6-phosphateC. Step 3: Phosphofructokinase-1 (PFK-1)1. Converts fructose 6-phosphate to fructose 1,6-bisphosphateD. Step 4: Aldolase Reaction1. Splits fructose 1,6-bisphosphate into G3P and DHAPE. Step 5: Isomerization of Triose Phosphates1. Converts DHAP into G3PF. Steps 6-10: Energy Capture Phase1. Step 6: Generates NADH and 1,3-bisphosphoglycerate2. Step 7: ATP production from 1,3-bisphosphoglycerate3. Step 10: Pyruvate production yielding ATP

VI. Energy Yield of Glycolysis

A. Yields 2 ATP per glucose (anaerobic)B. Can yield up to 32 ATP (aerobic)

VII. Regulation of Glycolysis

A. Key Steps and Control Points1. Hexokinase - Inhibited by glucose 6-phosphate2. PFK-1 - Regulated by energy state (ATP inhibits, AMP activates)3. Pyruvate kinase - Inhibited by ATP, activated by fructose 1,6-bisphosphateB. Control Strength and Pathway Flux1. Identifies enzymes with significant regulatory effects2. Reflects overall glycolytic throughput and efficiencyC. Glucagon and Glycolysis1. Promotes gluconeogenesis, inhibits glycolysis in the liver

VIII. Clinical Considerations

A. Pyruvate Kinase Deficiency1. Leads to hemolytic anemia2. Treatment: blood transfusions, therapiesB. Lactic Acidosis1. Increased lactate production during anaerobic metabolism2. Notable during shock or intense exercise.