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GLYCOLYSIS
Prof. S. Kajuna
Catabolism
Central Role of Glucose
Overview of glycolysis
Two phases of glycolysis
Two phases of glycolysis
Preparatory Phase
Reaction 1: phosphorylation
pg 526
Reaction 1: phosphorylation
Hexokinase vs. glucokinase
Tissue-specific
isozymes.
Reaction 2: isomerization
aldose
ketose
Reaction 2: isomerization
Reaction 3: phosphorylation
Reaction 3: phosphorylation
Reaction 4: cleavage
Reaction 4: cleavage
Reaction 5: isomerization
Reaction 5: isomerization
Keeping Track of Carbons
G3P
glucose
Reaction 6: oxidation
Reaction 6: oxidation
Reaction 7: substrate level phosphorylation
Reaction 8: shift of phosphoryl group
Reaction 8: shift of phosphoryl group
~Fig 14-8
Reaction 9: dehydration
Reaction 10: substrate level phosphorylation
Summary
Energy
investment
Cleavage
Energy
Harvest
https://www.youtube.com/watch?v=EfGlznwfu9U
Efficiency
Feeder
Pathways
 All
carbohydrate
s enter
glycolysis
 In muscle,
often via
hexokinase
glycerol
Glycerol 3-P
Fig 14-9
Fructose intolerance
Hereditary fructose intolerance results from a
defect in fructose breakdown in the liver, usually
in aldolase.
Glycogen
Breakdown
Glycogen
Breakdown
 Glycogen phoshorylase catalyzes the
simultaneous phosphorylation and cleavage of
an a-1,4 linked glucose from a non-reducing
end of glycogen.
 This reaction is called “phosphorolysis.”
Glycogen
Phosphorylase
Glycogen
Fig
15-12
Breakdown
Step 1.
Glycogen
Phosphorylase
Pyridoxal phosphate
Fig 14-12
Glycogen
Fig
15-12
Breakdown
Phosphoglucomutase
Fig 15-29
 G6P fate
depends on
tissue.
 In muscle,
G6P
proceeds
through
glycolysis.
 In liver, G6P
is converted
to glucose.
Limit Dextrins
Glycogen
Breakdown
Debranching
enzyme
Fig 15-28
Glycogen storage diseases
Fate of the products, pyruvate and NADH
Fig 143
Fig 143
Fermentation in Animals
Fermentation in Animals
• Lactic acid from skeletal muscle is sent into the
bloodstream.
• Lactate threshold occurs when production exceeds
clearance. Glycolysis cannot continue.
Cori Cycle
Fermentation in Yeast
Fermentation in Yeast
Pyruvate decarboxylase reaction
Alcohol dehydrogenase reaction
Regulation of
glycolysis
Irreversible steps are
regulated:
Hexokinase/Glucokinas
e
Phosphofructokinase I
Pyruvate Kinase
Control of Hexokinase
Glucose + ATP  G6P + ADP
Feedback inhibition by
G6P.
Tissue-specific
isozymes.
Control of PFK-1
Many allosteric effectors; e.g., ATP.
H+,
Control of PFK-1
ATP is an
allosteric
inhibitor of PFK1.
Two binding
sites: substrate
and allosteric
site.
Control of pyruvate kinase
PEP + ADP  pyruvate + ATP
Control of pyruvate kinase
Fig 15-19
Control of glycogen
phosphorylase
phosphorylation
phosphorylase b
(inactive)
phosphorylase a
(active)
glycogen
breakdown
Glycogen phosphorylase
is activated upon
phosphorylation by
phosphorylase kinase.
Glycogen phosphorylase
is activated upon
phosphorylation by
phosphorylase kinase.
Phosphorylase kinase is
activated upon
phosphorylation by protein
kinase A (PKA).
Glycogen phosphorylase
is activated upon
phosphorylation by
phosphorylase kinase.
Phosphorylase kinase is
activated upon
phosphorylation by protein
kinase A (PKA).
PKA is activated by
cyclic AMP, which is
produced by a G-protein in
response to
epinephrine/glucagon.
Fig 14-1
NADPH is
necessary to
protect against
reactive oxygen
species
Transketolase
requires
thiamine
pyrophospate
(TPP) as a
coenzyme
Ribose 5-P is
necessary in rapidly
dividing cells
Oxidative phase
•Rxns 1 and 3 produce NADPH
•Rxn 4 produces ribose-5phosphate
Glucose 6-P + 2 NADP+ + H2O 
Ribose 5-P + 2 NADPH + 2 H+ + CO2
From C1
Key Enzyme: G6P
Dehydrogenase
Case Study
Omar’s mother noticed that every time she
served falafel, her son complained of
feeling tired, hot, headachy, and sick to his
stomach. At first she thought he was just
being fussy, but sometimes he would
actually look yellow. Medical testing
confirmed hemolytic anemia. What’s up
with Omar?
Divicine leads to reactive
oxygen species
Favism!
A deficiency in G6PDH is the most common human enzyme
defect, affecting more than 400 million people worldwide.
Protective against malaria.
Case Study
Omar’s mother noticed that every time she
served falafel, her son complained of
feeling tired, hot, headachy, and sick to his
stomach. At first she thought he was just
being fussy, but sometimes he would
actually look yellow. Medical testing
confirmed hemolytic anemia. What’s up
with Omar?
X
Regulation
G6P
dehydrogenase is
allosterically
inhibited by
NADPH; activated
by NADP+
Oxidative Phase
Glucose 6-P + 2 NADP+ + H2O 
Ribose 5-P + 2 NADPH + 2 H+ + CO2
Some cells need NADPH but
not ribose 5-P
Ribose 5-P can be recycled
in the nonoxidative phase
Pentose Phosphate Pathway:
Nonoxidative Phase
Fig 14-22
Fig 14-23
Ribose
5-phosphate
Carbon Shuffling Reactions
Glucose
6-phosphate
Fig 14-23