Transcript Lh6Ch14aGlycolPPP

Chapter 14
Glycolysis, Gluconeogenesis,
and the
Pentose Phosphate Pathway
Part 1: Glycolysis
Glycolysis
Key topics: Things to Know
– Chemistry of each glycolytic reaction:
Forwards and Backwards.
– The general thermodynamics of each reaction.
– Other sugars entry to glycolysis.
– What to do with Pyruvate?
Central Importance of Glucose
• Glucose is an excellent fuel
– Yields good amount of energy upon oxidation
– Can be efficiently stored in the polymeric form
– Many organisms and tissues can meet their
energy needs on glucose only
• Glucose is a versatile biochemical
precursor
– Bacteria can use glucose to build the carbon
skeletons of:
•
•
•
•
All the amino acids
Membrane lipids
Nucleotides in DNA and RNA
Cofactors needed for the metabolism
Discoverers of Glycolysis (EMP Pathway)
Jacob Parnas
1884-1948
Showed that the sugar intermediates were
Phosphorylated
Glycolysis Overall
1 Glucose  2 Pyruvates
+ 2ATP
+ 2 NADH
10 Reactions: Know
them Backwards and
Forwards!!!!
Where is this going on in
a cell?
EOC Problems 1+2 can be
worked from this Figure and
Lactate Dehydrogenase Rxn
(slide 35)
Another View of
Glycolysis
What is This??
from KEGG
Pathways Linked to
Glycolysis, Enzymes by
EC numbers
Human enzymes in
green
Hexokinase
Phosphohexose Isomerase
Phosphofructokinase-1 (PFK-1)
Fructose-1,6-bisphosphate Aldolase
Keep Track of those Carbons!
EOC Problem
9..checks out the
carbons from triosephoshpates! Think
about the aldolase
ΔG.
TIM
3-P-Gyld DH
EOC Problem 14 is about arsenic poisoning and what
happens when arsenate is involved with this reaction.
3-PGA Kinase
3-PGA Mutase
Enolase is a Dehydrase
Pyruvate Kinase
A Fun Homework Problem
Add up all the ΔG’o ‘s and see how:
1. Aldolase’s endergonic ΔG is over come.
2. Total for Glycolysis…what enzymes are
doing the work?
But, is that all…what about REALITY?
EOC Problem 10: A look at modifying Glycolysis,
could it work?
The Real ΔG
Showed cancer cells had
high rate of glycolysis,
first to crystalize most
glycolytic enzymes.
Devised the first reliable,
quantitative O2 uptake
apparatus, lovingly called
a Warburg!..but replaced
by oxygen electrodes.
Nobel Prize, 1931
and trained 6 future Nobel
Laureates!! One of which
is Hans Krebs who
worked out the Citric Acid
Cycle.
Medical Aspect: CANCER
Most tumors: Glycolysis goes 10X faster than normal
cells. And is mainly fermentative (producing lactic
acid).
The strategy is to:
1. Use this in Detection
2. To slow glycolysis down in cancer cells.
Hypoxia Induced
Transcription Factor
Use of 6-Phospho-FdG in Positron Emission Tomography,
it accumulates in regions of high glycolytic activity
See next slide
CT and PET
Scans
Patient with malignant
melanoma –ingested 6Phospho-FdG
Left-CT scan –shows
location of bone, soft
tissue
Center-PET scan
showing high glucose
use.
Natural areas of high
glucose use: brain but
not bladder
Cancer has spread to liver, muscle
Right –false color composite
Type 1 Diabetes
and Glycolysis
Entry of other Sugars
Glycogen Phosphorylase
Entry of other Sugars
Conversion of Pyruvate to Something Else
Lactate DH
Why Lactate DH? Consider the Outputs of
Catabolism and Needs of Anabolism !
Lactate DH
Alligators do not have a great Cori Cycle
Alcohol Fermentation
EOC Problem 4: Calculating the Keq of Alcohol
Dehydrogenase (use Table 13-7)
EOC Problem 6: follow the carbons from glucose
into ethanol.
Entry of Glycerol into Glycolysis
Energetics of Glycerol as An Energy Source
Glycerol kinase
- ATP
Glycerol-3-P DH
+ NADH
3-P-Gyld DH
+ NADH
3-PGA Kinase
+ ATP
Pyr Kinase
+ ATP
Total
=
1 ATP + 2 NADH
Can GLYCEROL be FERMENTED?
Explain
Commercial Ethanol Fermentation
EOC Problem 7…all about the heat released from
fermentation…what’s going on?
Things to Know and Do Before Class
1. Each glycolytic reaction: substrates/products,
enzyme name, ΔGs.
2. Keep track of the carbon numbers from glucose
to pyruvate.
3. Overall glycolytic ΔG.
4. Getting other sugars and glycerol into
glycolysis.
5. EOC Problems: 1, 2, 4-7, 9, 10, 14.