Pentose Phosphate Pathway

Need help preparing for the Bio/Bio Chemistry section of the MCAT? MedSchoolCoach expert, Ken Tao, will teach everything you need to know about Pentose Phosphate Pathway of Metabolic Pathways which is a key component of the biochemistry section of the MCAT. Watch this video to get all the MCAT study tips you need to do well on this section of the exam!
Aside from glycolysis, another way that the body can oxidize glucose for use in the cells is through the pentose phosphate pathway (PPP). The pentose phosphate pathway runs parallel to glycolysis and occurs exclusively in the cytoplasm of cells. Furthermore, within the pathway, NADP+ serves as the electron acceptor and is reduced to NADPH. It is important to note that NADP+ and NADPH are not the same as NAD+ and NADH, and these two pairs of molecules serve opposite functions in the cell. Within the cell, NAD+ is at high concentrations, and NADH is at low concentrations. This concentration difference favors the reduction of NAD+ into NADH, allowing the cell to oxidize other compounds. In this way, NAD+ and NADH provide oxidizing power for the cell. Recall that NAD+ is used to oxidize glucose to release energy.
However, NADP+ and NADPH provide reducing power for the cell. In the cell, NADPH is at high concentrations, and NADP+ is at low concentrations. This concentration difference favors the oxidation of NADPH into NADP+, allowing the cell to reduce other compounds. This reduction capacity of the cell is useful for a variety of anabolic processes, for example, fatty acid, cholesterol, and steroid hormone synthesis, as well as, preventing oxidative damage from reactive oxygen species. In humans, the pentose phosphate pathway is responsible for about 60% of the body's NADPH production. Another product from the pentose phosphate pathway is ribose 5-phosphate, which is how the pathway gets its name. Ribose 5-phosphate is a pentose phosphate. Recall that ribose is a 5-carbon sugar, which is an essential component for nucleic acids. In other words, the pentose phosphate pathway produces a vital precursor of DNA, RNA, and other coenzymes such as NADH, FADH2, and coenzyme A.
Phases
There are two phases of the pentose phosphate pathway - the oxidative phase and the nonoxidative phase. The oxidative phase is irreversible. The overall reaction of the oxidative phase is:
Glucose 6-phosphate + 2(NADP+) + H2O → ribulose 5-phosphate + 2NADPH + 2(H+) + CO2
In the first step of the oxidative phase, glucose 6-phosphate is oxidized to 6-phosphoglucono-delta-lactone. Also, since glucose 6-phosphate is being oxidized, something else is being reduced. Here, NADP+ is being reduced to NADPH. This reaction is catalyzed by the enzyme glucose-6-phosphate dehydrogenase. Also, in this reaction, a lactone is generated, which is a cyclic carboxylic ester.
In the second step of the oxidative phase, 6-phosphoglucono-delta-lactone is hydrolyzed to 6-phosphogluconate by the enzyme lactase. This reaction is an example of hydrolysis, meaning that water is used to break one or more chemical bonds. In this step, water is used to break the ring cycle of pentose.
In the third step of the oxidative phase, 6-phosphogluconate is oxidized and decarboxylated to form ribulose 5-phosphate. Again, this step is an oxidative-reduction reaction, and since one compound is oxidized, another must be reduced. Here NADP+ is once again reduced to NADPH. This reaction is catalyzed by 6-phosphogluconate dehydrogenase.
In the last step of the oxidative phase, ribulose 5-phosphate is converted to ribose 5-phosphate by the enzyme phosphopentose isomerase.
The rest of the pentose phosphate pathway is the nonoxidative phase, which consists of a series of different reactions, which serve to convert ribose 5-phosphate into glycolytic intermediates. Ultimately, this process is reversible. The cell can choose, based on its needs, whether to run the pentose phosphate pathway, to produce ribose 5-phosphate or NADPH, or another metabolic pathway, such as glycolysis.
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