Pentose phosphate pathway

Every living organism has a set of blueprints in each of their cells called DNA and RNA. These blueprints are essential for life because they are the information on how to build the protein structures that make up each and everyone of us. Given the structural and functional importance of DNA and RNA for all living things, there are many layers of quality control to help avoid and correct mistakes when DNA and RNA are initially made.

While the products of glycolysis are sent through the rest of cellular respiration to produce energy (see video about glycolysis here), there is also an alternative branch off glycolysis to produce the sugars that make up DNA and RNA. This pathway, called the Pentose Phosphate Pathway, is special because no energy in the form of ATP, or adenosine triphosphate, is produced or used up in this pathway.

Similarly to some of the processes in cellular respiration, the molecules that go through the pentose phosphate pathway are mostly made of carbon. The easiest way to understand this pathway is to follow the carbon.

The breakdown of the simple sugar, glucose, in glycolysis provides the first 6-carbon molecule required for the pentose phosphate pathway. During the first step of glycolysis, glucose is transformed by the addition of a phosphate group, generating glucose-6-phosphate, another 6-carbon molecule. The pentose phosphate pathway can use any available molecules of glucose-6-phosphate, whether they are produced by glycolysis or other methods.

Now, we are ready to enter the first of two phases of the pentose phosphate pathway: 1) The oxidative phase and 2) The non-oxidative phase.

The “oxidative” word of this phase comes from the process of oxidation. Oxidation is the breakdown of a molecule as it loses at least one of its electrons.This phase is made up of 2 irreversible steps:

Glucose-6-phosphate is oxidized to form lactone. NADPH is produced as a byproduct of this reaction as NADP${}^{+}$‍ is reduced as glucose-6-phosphate is oxidized. Following the oxidation of glucose-6-phosphate, another reaction, catalyzed by a different enzyme, uses water to form 6-phosphogluconate, the linear product.

NADPH is similar in structure and function as the high energy electron shuttle, NADH, mentioned in the cellular respiration articles. NADPH has an added phosphate group and is used in the cell to donate its electrons, just like NADH. Once NADPH has donated its electrons it is said to be oxidized (oxidation = loss of electrons) and is now symbolized as, NADP${}^{+}$‍. NADPH is often used in reactions that build molecules and occurs in a high concentration in the cell, so that it is readily available for these types of reactions.

Next, a carbon is removed (cleaved) and CO${}_2$‍ is released. Once again, the electrons released from this cleavage is used to reduce NADP${}^{+}$‍ to NADPH. This new 5-carbon molecule is called ribulose-5-phosphate.

The non-oxidative phase is really handy because these reactions are reversible. This allows different molecules to enter the pentose phosphate pathway in different areas of the non-oxidative phase and be transformed up until the first molecule of the non-oxidative phase (ribulose-5-phosphate). Ribulose-5-phosphate is the precursor to the sugar that makes up DNA and RNA, and is also a product of the oxidative stage.

Ribulose-5-phosphate can be converted into two different 5-carbon molecules. One is the sugar used to make up DNA and RNA called, ribose-5-phosphate and this is the molecule we will focus on. Ribulose-5-phosphate isn’t being divided because the carbon count is the same in the next step.

The rest of the cycle is now made up of different options that depend on the cell’s needs. The ribose-5-phosphate from step 3 is combined with another molecule of ribose-5-phosphate to make one, 10-carbon molecule. Excess ribose-5-phosphate, which may not be needed for nucleotide biosynthesis, is converted into other sugars that can be used by the cell for metabolism.

The 10-carbon molecule is interconverted to create a 3-carbon molecule and a 7-carbon molecule. The 3-carbon product can be shipped over to glycolysis if it needs. That being said, recall that we can also work our way back up to another molecule in this phase. So that 3-carbon molecule could also be shipped over from glycolysis and transformed into ribose-5-phosphate for DNA and RNA production.

The 3-carbon molecule and the 7-carbon molecule, from the interconversion above in step 4, interconvert again to make a new 4-carbon molecule and 6-carbon molecule. The 4-carbon molecule is a precursor for amino acids, while the 6-carbon molecule can be used in glycolysis. The same reversal of steps in option 4 can happen here as well.

The pentose phosphate pathway takes place in the cytosol of the cell, the same location as glycolysis. The two most important products from this process are the ribose-5-phosphate sugar used to make DNA and RNA, and the NADPH molecules which help with building other molecules.

Oxidative phase:

Non-oxidative phase:

NADPH is readily available to donate its electrons in the cell because it occurs in such high concentration. Aside from helping build molecules, what kind of benefit is this really for the cell? NADPH is able to donate its electrons to compounds that fight dangerous oxygen molecules. These compounds are called antioxidants and you’ve probably heard about them being in some foods. Antioxidants donate electrons to neutralize dangerous oxygen radicals (super reactive oxygen molecules). Once they have given away their electrons, antioxidants need to quickly reload in case there are more oxygen radicals. NADPH is able to give antioxidants their constant flow of electrons to fight oxygen crime.

Cellular respiration articles: