Pathways of Carbohydrate Metabolism: Pentose Phosphate Pathway (HMP Shunt)

Introduction

The Pentose Phosphate Pathway (PPP), also known as the Hexose Monophosphate (HMP) shunt, is an alternative metabolic pathway for glucose utilization that provides important biochemical intermediates. It serves as a crucial source of reducing power in the form of NADPH and synthesizes pentoses required for nucleic acids.

Functions of the Pentose Phosphate Pathway

• NADPH Production: Essential for anabolic reactions, including fatty acid synthesis and maintaining cellular redox balance.
• Ribose-5-Phosphate Synthesis: Required for nucleotide and nucleic acid synthesis.
• Metabolic Intermediates: Provides molecules that integrate with glycolysis for energy production.

Phases of the Pentose Phosphate Pathway

Oxidative Phase

The oxidative phase is responsible for the generation of NADPH. It consists of irreversible reactions catalyzed by key enzymes.

1. Glucose-6-phosphate is oxidized by glucose-6-phosphate dehydrogenase (G6PD) to produce 6-phosphogluconate.
2. 6-Phosphogluconate undergoes further oxidation, forming ribulose-5-phosphate and releasing NADPH.

Non-Oxidative Phase

The non-oxidative phase generates pentose sugars for nucleic acid synthesis and converts excess ribose into glycolytic intermediates.

• Ribulose-5-phosphate is converted into ribose-5-phosphate, used for nucleotide synthesis.
• Additional rearrangement by transketolase and transaldolase creates intermediates like fructose-6-phosphate and glyceraldehyde-3-phosphate.

Clinical Relevance

Deficiency in glucose-6-phosphate dehydrogenase (G6PD) can lead to hemolytic anemia due to impaired ability to counter oxidative stress.

Conclusion

The Pentose Phosphate Pathway plays a vital role in metabolism by generating NADPH for anabolic processes and producing nucleotides essential for cell division and function.