Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway Part 1: Glycolysis Chapter 14.

Glycolysis, Gluconeogenesis, and the

Pentose Phosphate Pathway

Part 1: Glycolysis

Chapter 14

Glycolysis

– Chemistry of each glycolytic reaction: Forwards and Backwards.

– The general thermodynamics of each reaction.

– Other sugars entry to glycolysis.

– What to do with Pyruvate?

Key topics: Things to Know

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 Parnas1884-1948

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 triose-phoshpates! 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 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

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.