Pentose phosphate pathway

There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis phase, which involves the synthesis of five-carbon sugars. For most organisms, the pentose phosphate pathway takes place in the cytosol; in plants, most steps take place in plastids.

Like glycolysis, the pentose phosphate pathway appears to have a very ancient evolutionary origin. The reactions of this pathway are mostly enzyme-catalyzed in modern cells; however, they also occur non-enzymatically under conditions that replicate those of the Archean ocean, and are catalyzed by metal ions, particularly ferrous ions (Fe(II)). This suggests that the origins of the pathway could date back to the prebiotic world.

Outcome

The primary results of the pathway are:

• The generation of reducing equivalents, in the form of NADPH, used in reductive biosynthesis reactions within cells (e.g. fatty acid synthesis).
• Production of ribose 5-phosphate (R5P), used in the synthesis of nucleotides and nucleic acids.
• Production of erythrose 4-phosphate (E4P), used in the synthesis of aromatic amino acids in non-mammals.

Aromatic amino acids, in turn, are precursors for many complex biomolecules, including lignin in wood.

Dietary pentose sugars derived from the digestion of nucleic acids may be metabolized through the pentose phosphate pathway, and the carbon skeletons of dietary carbohydrates may be converted into glycolytic/gluconeogenic intermediates.

In mammals, the PPP occurs exclusively in the cytoplasm. In humans, it is most active in the liver, mammary glands, and adrenal cortex. The PPP is one of the three main ways the body creates molecules with reducing power, accounting for approximately 60% of NADPH production in humans.

One of the uses of NADPH in the cell is to prevent oxidative stress. It reduces glutathione via glutathione reductase, which converts reactive H₂O₂ into H₂O by glutathione peroxidase. Without NADPH, the H₂O₂ would be converted to hydroxyl free radicals by Fenton chemistry, which can attack the cell. Erythrocytes, for example, generate a large amount of NADPH through the pentose phosphate pathway to use in the reduction of glutathione.

Hydrogen peroxide is also generated by phagocytes in a process often referred to as a respiratory burst.