1. Pentose Phosphate Pathway
Five carbon sugars are produced, needed for DNA and RNA.
NADPH is produced for biosynthesis.
Reshuffling of carbons occurs to give products with three, four, six and seven carbons.
Anabolism is biosynthesis
The pentose phosphate pathway is an anabolic pathway.
It does two things to help with biosynthesis. It produces 5 carbon sugars that are needed for nucleotides (which are needed for DNA and RNA) The sugars are the ribose or deoxyribose part of the nucleotide triphosphate.
Also produceds NADPH for biosynthetic reactions. Difference between NADH and NADPH is a phosphate group otherwise they are functionally identical and yet the enzymes that recognize NADH will not bind to NADPH they are just totally different as far as that goes. And what that tag on there lets it keep its catabolic and anabolic reactions separate.
In addition once you have the 5 carbon sugars you can reshuffle the carbons to get different types of sugars. So you can get the different isomers and different size carbons. (3-7)

2. Fatty acid biosynthesis: taking acetyl CoA, 2 carbons at a time and linking them together build up a fatty acid.
Cholesterol biosynthesis: stitching together acetyl CoA and then reducing the carbons down to get reduced hydrocarbons that’s where NADPH is used to reduce the hydrocarbon chains and others.
Pretty much any biosynthetic pathway uses NADPH to drive it forward
In detoxification oxidized compounds are often reduced to detoxify and eliminate them.

3. 1. Oxidative – generation of NADPH 2. Nonoxidative – carbohydrate
PPP has two phases:
1. Oxidative – generation
of NADPH
2. Nonoxidative – carbohydrate
interconversions
Oxidative stage: a pathway that is essentially dedicated to anabolism and biosynthesis starting off with basically a catabolic reaction, it is an oxidation phase (little bit of oxidation here) but its purpose is not to get ATP but rather NADPH production so it has a slightly different purpose.
Then you have nonoxidative phase this is where the various sugars are produced. Involves a bunch of inverconversions of sugars where they can be used in metabolism.

4. Oxidation 6-phospho-D- glucono-d-lactone
The enzyme is named after its substrate it is oxidizing.
Electrons are moved from glucose-6-phosphate to create a lactone structure with a carbonyl group instead of a hydroxyl group.
This is the first reactant in the pathway.
6-phospho-D glucono-d-lactone

5. Oxidation
The lacton is hydrated by lactonase and becomes a carboxylic acid. We add water across this bond.
Typo on this slide it has an extra oxygen on it on the bottom the H-C-O the O shouldn’t be there.

6. Oxidation
The Carboxylic acid group is going to come off as CO2 and NADP+ gets turned into NADPH. So you get 2 NADPH produced from the oxidation of 1 glucose-6-phophate molecule. This is the essential function from the anabolic point of view of the pentose phosphate pathway is to make a lot of NADPH.
The reason why this is anabolic is because you don’t create any ATP or NADH you have NADPH.

7. Non-oxidative stage of PPP
Phase II: the nonoxidative phase. This phase has a lot of sugar interconversions. Don’t need to know all the structures.
Pay attention how this happens (the enzymes)
Riboulose 5 phosphate can be converted to D-ribose-5-phosphate which is an isomer. (enzyme is phosphopentose isomerase)
Or can be epimerized (an epimer can be produced, the structe on the right)

8. PP Shunt These are transaldolases and transketolases.
Transketolase moves carbons move 2 carbons. Takes them off one sugar and puts them on another you end up with one smaller sugar and one bigger by 2 carbons.

9. Pentose Phosphate Pathway
Transaldolases move 3 carbons at a time.

10. Pentose Phosphate Pathway
More transketolase
If you are doing enough of biosynthesis (your cells are making enough nucleotides) you will deplete the sugar pools and drive pentose phosphate pathway forward in other words you will draw more G6P in for more sugars and not NADPH but to generate more sugar residues. This is the second major function of the pentose phosphate pathway is to generate those sugar intermediates.

11. PPP: Nonoxidative phase
Produces important intermediates for nucleotide biosynthesis and glycolysis
Ribose-5-phosphate
Glyceraldehyde-3-phosphate
Fructose-6-phosphate
These intermediates here can be used for synthesis or catabolism (if the cell has enough sugar intermediates it will use them to burn them) It will take the NADH and recycle the sugar products back to catabolic purposes.
Examples:
Ribose-5-phosphate being used for nucleotide synthesis
Glyceraldehyde-3-phosphate can be oxidized in glycolysis
Fructose-6-phosphate can be fed into glycolysis
All of this stuff is happening in the cytoplasm so they are all using the same pool of intermediates.

12. If the cell requires more NADPH. than ribose molecules,
If the cell requires more NADPH than ribose molecules, products of the nonoxidative phase can be shuttled into glycolysis
Example of a red blood cell which consumes a lot of NADPH to protect itself from oxidative damage from the oxygen free radicals. You end up with a lot of free radical damage in red blood cells that can be reversed by glutathione (reducing agent in the cytoplasm that can reverse oxidative events)
Red blood cells produce a lot of NADPH but don’t do a lot of energetic activity. So the non-oxidative products can be shuttled back into glycolysis or some place else for other cells to be used.

14. Hemolytic Anemia NADPH generated by PPP protects against ROS
The PP Pathway supplies NADPH in red blood cells.
Glucose-6-phosphate dehydrogenase deficiency leads to less NADPH, less reduced glutathione (a peptide needed to maintain sulfhydryl groups and to keep iron as iron(II) in hemoglobin) thus anemia develops.
Over 100 million people have the deficiency which conveys some resistance to malaria.
This is a condition caused by a faulty pentose phosphate pathway. Its because individuals with this can’t produce much NADPH and they can’t regenerate reduced glutathione. So they can’t protect from oxidative damage so as a result the red blood cells (especially hemoglobin) undergoes oxidative damage and the hemoglobin becomes denatured and dysfunctional and the red blood cells can no longer carry oxygen. You get to be anemic. Also the red blood cells themselves are damaged and they are destroyed. So there needs to be NADPH to maintain the sulfhydrl groups on glutathione in the reduced condition.
These sick red blood cells are not good homes for plasmodium they can’t effect individuals as effectively with this condition. So on one hand you have anemia but at the same time you are resistance to malaria. Sickle cell anemia is also resistant to plasmodia.

15. Hemolytic Anemia Glutathione Reduced form provides H to
This is the reaction that gets you the reduced glutathione. The NADPH is oxidized back to NADP+ so it needs to go back through the pentose phosphate pathway to get re-reduced.
The glutathione can then go around an undo oxidative damage by reducing the oxidative states in proteins and lipids.
Reduced form provides H to
reduce protein disulfide links

16. Heinz bodies – clumps of denatured hemoglobin
The red blood cells have clumps of hemoglobin in there and become less capable of carrying oxygen.
Heinz bodies – clumps of denatured hemoglobin
G-6-P Dehydrogenase Deficiency patients are susceptible
to drug-induced hemolytic anemia
Pamaquine generates peroxides that kill plasmodium but
destroy RBC’s in G6PDD patients

17. Malaria plasmodium.