0.28 Bis2a 07.4 pentose phosphate pathway

Intro into the pentose pathway

In most introductory biology and biochemistry courses focus on glycolysis (oxidation of glucose to pyruvate) and the TCA cycle, the oxidation of pyruvate to acetyl~CoA and the eventual complete oxidation to CO ₂ . While these are extremely important and universal reactions, most courses leave out the pentose phosphate pathway or hexose monophosphate shunt. This pathway, like the TCA cycle is partially cyclic in nature, where 3 glucose molecules enter and 2 glucose and 1 glyceraldyde-3-phosphate leave. The 2 glucose molecules can recycle and the G3P enters glycolysis. Its an important pathway because it is the primary mechanism for the formation of pentoses, the five carbon sugar required for nucleotide biosynthesis as well as the formation of a variety of other essential cellular components and NADPH, the cellular reductant primarily used in anabolic reactions.

A note from the instuctor

Oxidatvie pentose phosphate pathway: aka the hexose monophosphate shunt

While glycolysis has evolved to oxidize hexoses to form carbon precursors for biosynthesis, energy (ATP) and reducing power (NADH) the Pentose Phosphate Pathway (PPP) has evolved to utilize pentoses or five carbon sugars. Pentose are required precursors for nucleotides and other essential biomolecules. The PPP also generates NADPH instead of NADH, which is required for most anabolic reactions. The PPP, in conjuction with Glycolysis and the TCA cycle make up what we call Central Metabolism. These 3 central pathways (along with the reaction Pyruvate to Acetyl~CoA) are responsible for producing all of the necessary precursor molecules required by all cells. The PPP is responsible for producing pentos-phosphates (5 carbon sugars), Eyrthrose-phosphate (four carbon sugars)and NADPH . This pathway is also responsible for the production of Sedoheptulose -phosphate , an essential 7-carbon sugar used in the outer cell membranes of Gram-negative bacteria.

Below is a diagram of the pathway. The pathway is complex and involves a variety of novel rearrangement reactions that move two and three carbon units around. These reactions called transaldolase and transketalase 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 3 glucose-6-Phosphate (in green) molecules being oxidized to form 3 CO ₂ molecules, 1 glyceraldehyde-Phosphate (in red), and 2 hexose-phosphates (in red). In this cycle, the formed glyceradehyde-Phosphate feeds into glycolysis and the 2 hexose-Phosphates (glucose-Phosphates) can recycle into the PPP or gycolysis.

As shown in Figure 2, the net result of the pathway is 1 trios-phosphate (glyceraldehyde-3-Phosphate) that can then be further oxidized via glycolysis; 2 recycled hexose-phosphates (in the form of either glucose-6-phosphae or fructose-6-phosphate) and NADPH which is required reductant for many biosynthetic (anabolic) reactions. The pathway provides a variety of intermediate sugar-phosphates that the cell may require, such as pentose-phosphates (for nucleotides and some amino acids), erythrose-phosphate (for amino acids) and sedohepulose-phosphate, for Gram-negative bacteria.

The PPP along with glycolysis, the TCA cycle and the oxidation of Pyruvate to acetyl-Co makes up the major pathways of central metabolism and is required to some degree of all organisms to construct the basic substrates to create the building blocks of life.

Section summary

By the end of this module you should be able to describe the role the pentose phosphate pathway plays in central metabolism. Determine the end-products of the pathway.