Glucose Utilization and Biosynthesis

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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
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