– Chemistry of each glycolytic reaction:
Forwards and Backwards.
– The general thermodynamics of each reaction.
– Other sugars entry to glycolysis.
– What to do with Pyruvate?

– 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
– 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 O
2 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 6-
Phospho-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

Why Lactate DH? Consider the Outputs of
Catabolism and Needs of Anabolism !
Lactate DH

Alligators do not have a great Cori Cycle

EOC Problem 4: Calculating the K eq 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
Glycerol-3-P DH
3-P-Gyld DH
3-PGA Kinase
Pyr Kinase
Total =
- ATP
+ NADH
+ NADH
+ ATP
+ ATP
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.