Pentose Phosphate Pathway Notes

Also known as the hexose monophosphate shunt.
Occurs in the cytoplasm of all cells.
Serves two major functions:
- Production of NADPH.
- Source of ribose-5-phosphate for nucleotide synthesis.

Begins with glucose-6-phosphate.
Ends with ribulose-5-phosphate.
Irreversible.
Produces NADPH.
Involves the rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD).
- G6PD is induced by insulin. The abundance of sugar entering the cell under insulin stimulation will be shunted into glycolysis and aerobic respiration (fuel utilization pathways), as well as fatty acid synthesis and glycogenesis (fuel storage pathways) and the PPP
- Inhibited by NADPH and activated by NADP+.

Begins with ribulose-5-phosphate.
Represents a series of reversible reactions.
Produces an equilibrated pool of sugars for biosynthesis, including ribose-5-phosphate.
Fructose-6-phosphate and glyceraldehyde-3-phosphate (glycolysis intermediates) are produced therefore intermediates can feed back into glycolysis.
Pentoses can be made from glycolytic intermediates without going through the G6PD reaction.
Interior conversions are primarily accomplished by the enzymes transketolase and transaldolase.

NAD+ acts as a high-energy electron acceptor (oxidizing agent).
- NADH produced from NAD+ reduction feeds into the electron transport chain to indirectly produce ATP.
NADPH acts as an electron donor (reducing agent).
Cells require NADPH for:
- Biosynthesis, mainly of fatty acids and cholesterol.
- Assisting in cellular bleach production in certain white blood cells (bactericidal activity).
- Maintenance of a supply of reduced glutathione to protect against reactive oxygen species (antioxidant).

Hydrogen peroxide ( $H<em>2O</em>2$ ) is produced as a byproduct in aerobic metabolism and can break apart to form hydroxide radicals ( $OH$ ).
Free radicals can attack lipids (including those in the phospholipids of the membrane).
Oxidized lipids lose their function, weakening the membrane and causing cell lysis.
Red blood cells are especially susceptible due to high oxygen levels, which can be oxidized by free radicals to become superoxide radicals ( $O_2$ ).
Free radicals can also damage DNA, potentially causing cancer.
Glutathione is a reducing agent that can help reverse radical formation before damage is done to the cell.

Carbohydrate metabolism processes that do not require oxygen are heavily tested, as is their integration.
The body can use, store, or create fuel 24/7 based on internal and external demands.
Pathways are regulated (turned on/off) as needed.
Acetyl CoA (downstream product of glycolysis) can turn off glycolysis, allowing the storage of extra sugar or the generation of new sugar if needed.
The next chapter will cover oxygen-requiring carbohydrate metabolism processes, including the citric acid cycle, electron transport chain (ETC), and oxidative phosphorylation.