Chapter 14.1 and 14.2: Glycolysis and Feeder

Pathways

CHEM 7784

Biochemistry

Professor Bensley

CHAPTER 14.1 and 14.2 Glycolysis

– Process of harnessing energy from glucose via glycolysis

– Various pathways by which carbohydrates other than glucose enter glycolysis

Today’s Objectives: To learn and understand the

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 enzyme-catalyzed 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 6-Carbon Sugars

• Step four is the cleavage of Fructose 1,6-Bisphosphate

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 3-Phosphoglycerate 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 Substrate-Level Phosphorylation

… but loss of phosphate from phosphoenolpyruvate yields an enol that tautomerizes into ketone

Feeder Pathways for Glycolysis