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Lecture 6 Slides
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Warburg Effect
the Warburg effect is the observation that most cancer cells
predominantly produce energy by a high rate of glycolysis
followed by lactic acid fermentation in the cytosol
Otto Heinrich
Warburg
1931
Nobel Prize
in Medicine
Warburg Effect
Getting
other
sugars
into the
glycolytic
pathway
fig 14-10
A second route for fructose (in liver)
pg 545
Glycogen: nature’s sugar bowl
Liberating glucose units from glycogen
fig 14-11
more about glycogen later
From glycogen to glycolysis…
phosphoglucomutase
another mutase…
Now what?
fig 14-1
Now what?
fig 14-1
Now what?
Fermentation: anaerobic
metabolism of glucose
without oxidation...
fig 14-1
LDH converts pyruvate to lactate,
restoring the pool of NAD+
pg 547
LDH converts pyruvate to lactate,
restoring the pool of NAD+
pg 547
ethanol production: another NAD+ restoration strategy
pg 547
Thiamine pyrophosphate (TPP): an activated carbon
fig 14-14
Thiamine pyrophosphate in ethanol production
fig 14-14
TPP as a
carbanion
nucleophile
in pyruvate
metabolism
fig 14-14
TPP as a carbanion
nucleophile in pyruvate
metabolism
fig 14-14
TPP as a carbanion
nucleophile in pyruvate
metabolism
fig 14-14
TPP-mediated enzymatic reactions
TPP is all about carbonyl activation
table 14-1
The glycolysis energy landscape
(pyruvate set to 0)
Regulated glycolytic enzymes
hexokinse (and glucokinse)
regulated by G6P allosterically
liver isozyme is glucokinase, different
phosphofructokinase (PFK-1)
pyruvate kinase
regulated by ATP, citrate, and fatty acids
The glycolysis energy landscape
(pyruvate set to 0)
regulation of hexokinase: isozymes can differ
fig 15-12
PFK-1 :
a right
fancy
enzyme!
fig 15-14
PFK-1: allosteric regulation by ATP, etc…
fig 15-14
PFK-1: allosteric regulation by ADP, etc…
xxx
FPK-1 has multiple allosteric regulators
fig 15-14
Our book’s notation for regulators
inhibition
fig 15-14
activation
PFK-1 has multiple allosteric regulators
fig 15-14
Pentose
phosphate
pathway
oxidative
reactions
fig 14-21
Glucose as
a source of
other stuff
Pentose
phosphate
pathway
oxidative
reactions
fig 14-21
Pentose
phosphate
pathway
oxidative
reactions
fig 14-21
Pentose
phosphate
pathway
oxidative
reactions
fig 14-21
Pentose phosphate pathway: non-oxidative rxns
all movement
of carbonyl groups
to and fro…
fig 14-22
Pentose
phosphate
pathway:
nonoxidative
reactions
2C
3C
2C
2C
2C
fig 14-22
3C
end of lecture 6
LDH
converts
pyruvate
to lactate,
restoring
the pool
of NAD+
pg 547