The document summarizes the pentose phosphate pathway, which has four main purposes: maintaining carbon balance, providing precursors for synthesis of nucleotides and amino acids, producing the reducing agent NADPH, and combating oxidative stress. The pathway occurs in the cytoplasm of nearly all cells, especially liver and red blood cells, and involves both oxidative and non-oxidative stages to produce NADPH, trioses, hexoses, and pentoses from glucose-6-phosphate. Ribulose-5-phosphate produced in this pathway can be converted into other intermediates that re-enter glycolysis or are used for nucleotide synthesis. NADPH produced helps reduce hydrogen peroxide to water through the glutathione system, combating oxidative stress

1. SBCH212/4BCH212: Metabolism
Department of Biochemistry and Microbiology
Faculty of Science and Agriculture
University of Zululand
KwaDlangezwa, 3886
South Africa
Miss T Padayachee

3. Pentose Phosphate Pathway
The importance of this pathway:
1. Maintains carbon homeostasis (balance)
2. Provides precursors for nucleotide and amino acid synthesis
3. Produces NADPH that is required as a co-factor for major enzymes
4. Defeats oxidative stress
Occurs virtually in all cells but mostly in the liver and RBCs
Occurs in the cytoplasm
Produces NADPH
Produces Trioses, Hexoses and Pentoses
Pentoses are needed for nucleotide synthesis

4. Pentose Phosphate Pathway
Split into oxidative (irreversible) and non-oxidative (reversible) stages
Begins with Glucose-6-Phosphate (G6P)
Instead of G6P entering the glycolysis cycle, it gets shunted into this pathway
G6P becomes glucono-1,5-lactone-6P
Glucose-6-phosphate dehydrogenase catalyses this reaction
NADP+ is reduced to NADPH
This is a RATE LIMITING STEP

5. Pentose Phosphate Pathway
The product of this reaction (NADPH) inhibits Glucose-6-phosphate
dehydrogenase
Low levels of NADPH will activate the enzyme , High levels of NADPH will
inhibit the enzyme

6. Pentose Phosphate Pathway
Glucono-1,5-lactone-6-phosphate is converted to 6-phosphogluconate
Lactonase is the enzyme that catalyses this reaction, water is added
6-phosphogluconate is converted to Ribulose-5-phosphate
6-phosphogluconate dehydrogenase catalyses this reaction
NADP+ is reduced to NADPH, CO2 is released
STEP 1 and STEP 3 produce NADPH

7. Lactonase and H2O

9. Pentose Phosphate Pathway
Ribulose-5-phosphate can be converted into various intermediates
1. It can be converted into Xylulose-5-phosphate
• Ribulose-phosphate-3-epimerase catalyses this reaction
• Xylulose-5-phosphate can be converted to Fructose-6-phosphate which then
enters the glycolysis cycle.
 If your body requires NADPH, it will shunt G6P into this pathway, produce
NADPH in step 1 and 3 and thereafter return back to the glycolysis cycle using
the above step

11. Pentose Phosphate Pathway
Ribulose-5-phosphate can be converted into various intermediates
2. Ribose – 5 – phosphate
• Ribose phosphate isomerase catalyses this reaction
• Ribose -5-phosphate is converted into 5-phosphoribosyl-1-pyrophosphate
(PRPP)
• This molecule is very important as it is involved in purine and pyrimidine
synthesis (DNA)
• The breakdown of nucleotides, can produce ribose-5-phosphate which can enter
the glycolysis cycle by being converted back to ribulose-5-phosphate

13. Pentose Phosphate Pathway
Ribose-5-phosphate and Xylulose – 5 – phosphate can be converted into
glycolysis intermediates
Ribose-5-phosphate can be converted to seduheptulose-7-phosphate by the
enzyme transketolase
Seduheptulose-7-phosphate can be converted to fructose-6-phosphate by the
enzyme transaldolase
Phosphohexose isomerase will convert F6P into G6P which enters the glycolysis
cycle

14. Pentose Phosphate Pathway
Xylulose-5-phosphate can be converted to glyceraldehyde-3-phosphate by the
enzyme transketolase
Glyceraldehyde-3-phosphate can be converted to erythrose-4-phosphate by the
enzyme transaldolase
Transketolase will convert erythrose-4-phosphate into Fructose-6-phosphate
F6P will be converted into G6P by Phosphohexose isomerase
G6P enters the glycolysis cycle

16. Pentose Phosphate Pathway
 Why do we require NADPH?
 Defeats oxidative stress
• Hydrogen peroxide is toxic to the human body and needs to be converted to its
less harmful form of H2O
• Hydrogen peroxide can arise from various metabolic errors and drugs
• NADPH can be oxidized by glutathione reductase, this enzyme will take the
protons from NADPH and reduces glutathione.
• Glutathione peroxidase will take the protons from glutathione and reduces
hydrogen peroxide into water (H2O).
• Hence why we require NADPH and therefore the Pentose Phosphate Pathway
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