Pentose phosphate pathway

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The pentose phosphate pathway (PPP), also known as the phosphogluconate pathway and the hexose monophosphate shunt, is a metabolic pathway parallel to glycolysis. It generates NADPH and pentoses (5-carbon sugars) as well as ribose 5-phosphate, a precursor for the synthesis of nucleotides. While it does not produce ATP, it is crucial for anabolic reactions and antioxidant defense.

Overview

The pentose phosphate pathway consists of two distinct phases: the oxidative phase and the non-oxidative phase.

Oxidative Phase

In the oxidative phase, glucose-6-phosphate is oxidized to produce NADPH and ribulose 5-phosphate. The key enzyme in this phase is glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the first step and is a major control point of the pathway.

Non-Oxidative Phase

The non-oxidative phase involves the interconversion of sugars. Ribulose 5-phosphate is converted into ribose 5-phosphate and other sugars such as xylulose 5-phosphate. These sugars can then enter glycolysis or be used in the synthesis of nucleotides and nucleic acids.

Functions

The pentose phosphate pathway serves several critical functions:

• **NADPH Production**: NADPH is essential for biosynthetic reactions, including fatty acid synthesis and cholesterol synthesis, and for maintaining the reduced glutathione pool in cells.
• **Ribose 5-Phosphate Production**: This sugar is a precursor for the synthesis of nucleotides and nucleic acids.
• **Metabolic Flexibility**: The pathway provides a means to metabolize pentoses and to interconvert sugars for various biosynthetic needs.

Regulation

The pentose phosphate pathway is primarily regulated at the level of glucose-6-phosphate dehydrogenase. The activity of G6PD is influenced by the cellular levels of NADP+ and NADPH. High levels of NADPH inhibit the enzyme, while high levels of NADP+ activate it.

Clinical Significance

Deficiencies in glucose-6-phosphate dehydrogenase can lead to G6PD deficiency, a genetic disorder that affects red blood cells and can result in hemolytic anemia. This condition is often triggered by certain foods, infections, or medications.

See Also

• Glycolysis
• Citric acid cycle
• Gluconeogenesis
• Metabolism