Glycolysis and the Pentose Phosphate Pathway

Now we're getting into the nitty-gritty details! (At least it's pretty easy to see the relevance of this lecture though :P)

Describe the reactions of glycolysis and the mechanism of energy production in the cytosol.  

Glycolysis, as you should know, is a pathway in which glucose is broken down to form energy. The main end product of glycolysis is pyruvate, which has three different fates: in the presence of oxygen, it can be converted to acetyl-CoA and enter the citric acid cycle; in anaerobic conditions, it can form lactate; and in some organisms it can be broken down to ethanol (such as in the fermentation process in yeast).

Glycolysis has two major phases: the preparatory phase and the payoff phase. (Not sure if those are official names, but they're on the slides.) In the first phase, 6-carbon glucose is converted into two 3-carbon sugars called glyceraldehyde 3-phosphate. In the second phase, glyceraldehyde 3-phosphate is converted into pyruvate, generating ATP and NADH. It should be noted that glucose is not the only fuel that can enter this pathway: it's the main fuel, but other sugars can enter the pathway at different stages.

Phase 1: Preparatory Phase

The preparatory phase consists of five steps:

1. Glucose --> Glucose 6-phosphate. Requires ATP and the enzyme hexokinase.
2. Glucose 6-phosphate <--> Fructose 6-phosphate. Requires the enzyme phosphohexose isomerase.
3. Fructose 6-phosphate --> Fructose 1,6-bisphosphate. Requires ATP and the enzyme phosphofructokinase-1.
4. Fructose 1,6-bisphosphate <--> Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. Requires the enzyme aldolase.
5. Conversion of dihydroxyacetone phosphate into glyceraldehyde 3-phosphate (so you end up with 2 molecules of glyceraldehyde 3-phosphate for every molecule of glucose). Requires the enzyme triose phosphate isomerase.

Note that 2 molecules of ATP are required (steps 1 and 3). Don't worry- we'll more than make up for that later.

Phase 2: Payoff Phase 

The payoff phase also consists of five steps:

1. Glyceraldehyde 3-phosphate <--> 1,3-bisphosphoglycerate. Requires the enzyme glyceraldehyde 3-phosphate dehydrogenase. During this step, NAD⁺ is also reduced to NADH, with a little help from HPO₄^2- which supplies the hydrogen.
2. 1,3-bisphosphoglycerate <--> 3-phosphoglycerate. Requires the enzyme phosphoglycerate kinase. Produces ATP. (1 molecule of ATP is produced for each molecule of 1,3-bisphosphoglycerate, but since one molecule of glucose produces two molecules of 1,3-bisphosphoglycerate, you actually get 2 molecules of ATP for every 1 molecule of glucose.
3. 3-phosphoglycerate <--> 2-phosphoglycerate. Requires the enzyme phosphoglycerate mutase.
4. 2-phosphoglycerate <--> Phosphoenolpyruvate. Requires the enzyme enolase. Produces some water.
5. Phosphoenolpyruvate --> Pyruvate. Requires pyruvate kinase. Produces ATP (the ATP yield of this step is the same as the yield for step 2 of this pathway).

As you can see, this pathway has two ATP-producing steps (2 and 5). These steps combined produce 4 molecules of ATP for every molecule of glucose. As 2 molecules of ATP were consumed in the first half, this results in a net yield of 2 ATP molecules per molecule of glucose.

Explain the difference between reversible and irreversible reactions.

Reversible reactions are reversible while irreversible reactions are irreversible...? Also, the reversible reactions tend to have a small free energy change, whereas irreversible reactions have a much larger one (I think).

The three irreversible reactions in the glycolysis pathway are steps 1 and 3 of the first phase as well as the final step of the second phase.

Have an understanding of the purpose of the pentose phosphate pathway.

The pentose phosphate pathway produces pentose sugars, such as ribose 5-phosphate, that are required for the production of nucleotides (and, by extension, DNA and RNA). Along the way, NADPH is formed, which is required for biosynthesis of fatty acids and production of glutathione (GSH).

The first step of this pathway is catalysed by glucose-6-phosphate dehydrogenase (G6PDH). If this is deficient, the red blood cell membrane might be lost, leading to haemolysis and haemolytic anaemia.