Chapter 14.1 and 14.2: Glycolysis and Feeder Pathways CHEM 7784 Biochemistry Professor Bensley CHAPTER 14.1 and 14.2 Glycolysis Today’s Objectives: To learn and understand the – Process of harnessing energy from glucose via glycolysis – Various pathways by which carbohydrates other than glucose enter glycolysis Central Importance of Glucose • Glucose is an excellent fuel • Glucose is a versatile biochemical precursor • Four major pathways of glucose utilization Glycolysis: The Big Picture •Anaerobic process carried out by all cells but at different rates •Converts hexose to two pyruvates •Generates 2 ATP and 2 NADH •For certain cells in the brain and eye, glycolysis is the only ATP generating pathway Glucose + 2 ADP + 2 NAD+ + 2Pi 2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2H20 Glycolysis: Importance • Glycolysis is a sequence of ten enzymecatalyzed reactions by which glucose is converted into pyruvate • Two phases: – First phase converts glucose to two G-3-P – Second phase produces two pyruvate molecules • Three possible fates for pyruvate Glycolysis: The Preparatory Phase Glycolysis: The Payoff Phase STEP 1 - The Hexokinase Reaction • The first step, phosphorylation of glucose, is catalyzed by hexokinase in eukaryotes, and by glucokinase in prokaryotes • This process uses the energy of ATP STEP 2 - Phosphohexose Isomerization • An aldose can isomerize into ketose via an enediol intermediate • Overall – Glucose-6-Phosphate is converted to Fructose-6-Phosphate STEP 3 - The Second Priming Reaction; The First Commitment • This is an irreversible step • The product, fructose 1,6-bisphosphate is committed to become pyruvate and yield energy STEP 4 - Aldolases Cleave 6Carbon Sugars • Step four is the cleavage of Fructose 1,6Bisphosphate STEP 5 - Triose Phosphate Interconversion • DAP is converted enzymatically to GAP STEP 6 - Glyceraldehyde 3-Phosphate Dehydrogenase Reaction • First step in the “Payoff Phase” of Glycolysis • First energy-yielding step in glycolysis STEP 7 - First Substrate-Level Phosphorylation • 1,3-bisphosphoglycerate is a high-energy compound that can donate the phosphate group to ADP to make ATP STEP 8 - Conversion of 3Phosphoglycerate to 2-Phosphoglycerate • This is a reversible isomerization reaction Mechanism of the Phosphoglycerate Mutase Reaction STEP 9 - Dehydration of 2-Phosphoglycerate • The goal here is to create a better phosphoryl donor • Loss of phosphate from 2-phosphoglycerate would merely give a secondary alcohol with no further stabilization … STEP 10 - Second SubstrateLevel Phosphorylation … but loss of phosphate from phosphoenolpyruvate yields an enol that tautomerizes into ketone Feeder Pathways for Glycolysis