Discussions of metabolism in most introductory biology courses focus on glycolysis (oxidation of glucose to pyruvate) and the TCA cycle (oxidation of pyruvate to acetyl-CoA and the eventual complete oxidation to CO2). While these are important and universal metabolic pathways, many courses leave out the pentose phosphate pathway (PPP), also known as the hexose monophosphate shunt. In this class, we consider the PPP important for two key reasons. First, it is the primary route for the formation of pentoses, the five-carbon sugar required for nucleotide biosynthesis and a variety of other essential cellular components. Second, redox reactions in the PPP generate NADPH, the main mobile electron donor used in anabolic (building) reactions.
A note from the instructor
Like the modules on glycolysis and the TCA cycle, we do not expect students to memorize specific compound names or details of molecular structures in the pathway. We provide those details in the reading so you can understand the transformations occurring in this pathway and refer back to them when needed. Rather than memorizing, focus instead on the mastering the assigned learning goals related to the PPP.
Oxidative pentose phosphate pathway: a.k.a., the hexose monophosphate shunt
We call glycolysis, the TCA cycle and the pentose phosphate pathway central carbon metabolism. These three pathways (along with the reaction that converts pyruvate to acetyl-CoA) contain all the chemical precursors required by cells for the biosynthesis of nearly all other biomolecules. The PPP produces pentose phosphates (five-carbon sugars), eyrthrose-phosphate (a four-carbon sugar), and NADPH. The pentose phosphates are key precursors for nucleotide biosynthesis while NADPH serves as the main mobile electron donor for anabolic (building) reactions. The PPP also produces sedoheptulose-phosphate, an essential seven-carbon sugar used in the building of Gram-negative bacteria's outer cell membranes.
Below is a diagram of the pathway. The pathway involves several redox reactions and multiple molecular rearrangement that interconvert molecules of 3-, 4-, 5-, 6-, and 7-carbons. The pathway begins with the oxidation of Glucose-6-phosphate (G6P), a key intermediate of glycolysis, by the enzyme glucose-6-phosphate dehydrogenase (G6PDH). This enzyme oxidizes G6P through the coupled reduction of the electron carrier NADP+ to make NADPH. Enzymes called transaldolases and transketalases are used to produce the intermediates within the pathway. The net result is oxidation and subsequent decarboxylation of glucose to form a pentose. The total reaction involves three glucose-6-phosphate (in green) molecules being oxidized to form three CO2 molecules, one glyceraldehyde-phosphate (in red), and two hexose-phosphates (in red). In this cycle, the formed glyceradehyde-phosphate feeds into glycolysis and the two hexose-phosphates (e.g., glucose-phosphates) can recycle into the PPP or glycolysis.
As shown in the figure above, products of the pathway include glyceraldehyde-3-phosphate. This sugar can then be further oxidized via glycolysis. Fructose-6-phosphate that can reenter glycolysis and NADPH, a reductant for many biosynthetic (anabolic) reactions is also made. In addition, the pathway provides a variety of intermediate sugar-phosphates that the cell requires, such as pentose-phosphates (for nucleotides and some amino acids), erythrose-phosphate (for amino acids) and sedohepulose-phosphate (for gram-negative bacteria). The figure below illustrates the input-output relationship between PPP and the "top half" of glycolysis.
Figure 2. The relationship between glycolysis and PPP.
The Pentose Phosphate Pathway is shown as a "shunt" (alternative metabolic pathway) for glucose-6-phosphate.
Attribution: Marc T. Facciotti