The pentose phosphate pathway (PPP) is a crucial metabolic route that diverges from the linear pathways typically seen in cellular metabolism. Unlike glycolysis, which has a straightforward input-output relationship, the PPP functions more like a web, allowing for multiple inputs and outputs. The pathway primarily begins with glucose 6-phosphate, which is converted into various important products, including ribulose 5-phosphate and NADPH.
In its simplest form, the PPP converts glucose 6-phosphate into two molecules of NADPH and one molecule of ribulose 5-phosphate. Ribulose 5-phosphate is essential for synthesizing ribose 5-phosphate, a key component in nucleotide and histidine synthesis. The pathway is unique in that it can fully oxidize glucose, unlike glycolysis, which only partially oxidizes it. This full oxidation occurs through a series of reactions that generate NADPH, a molecule similar to NADH but distinguished by the presence of an additional phosphate group.
The initial reactions of the PPP involve specific enzymes. The first reaction, catalyzed by glucose 6-phosphate dehydrogenase, converts glucose 6-phosphate into 6-phosphogluconolactone while producing NADPH. The second reaction, facilitated by lactonase, breaks the lactone ring to form 6-phosphogluconate. The third reaction, carried out by 6-phosphogluconate dehydrogenase, further processes this molecule to yield ribulose 5-phosphate and another NADPH.
Once ribulose 5-phosphate is formed, it can be converted into ribose 5-phosphate or xylulose 5-phosphate through the action of phosphopentose isomerase. Both of these 5-carbon sugars are necessary for subsequent reactions. The transketolase enzyme transfers 2-carbon units from xylulose 5-phosphate to ribose 5-phosphate, resulting in the formation of a 7-carbon molecule, heptulose 7-phosphate, and glyceraldehyde 3-phosphate (G3P), a key intermediate in various metabolic pathways. Following this, transaldolase transfers 3-carbon units from heptulose 7-phosphate to G3P, producing erythrose 4-phosphate and fructose 6-phosphate, both of which are vital for further biosynthetic processes.
NADPH plays a significant role in cellular defense against oxidative stress. It is utilized by superoxide dismutase to convert harmful superoxide radicals into hydrogen peroxide, which, while still reactive, is less dangerous than superoxide. Subsequently, glutathione reductase uses NADPH to regenerate reduced glutathione from its oxidized form, allowing the cell to neutralize hydrogen peroxide into harmless water. Additionally, NADPH regulates the PPP through feedback inhibition; excessive NADPH levels signal the cell to reduce glucose entry into the pathway, maintaining metabolic balance.
