Pentose Phosphate Pathway - Oxidative Phase

Summary

The pentose phosphate pathway begins with glucose-6-phosphate, a molecule which itself has several metabolic fates. Glucose-6-phosphate is usually thought of as coming from glycolysis, which helps explains its other name: the hexose monophosphate shunt. This is because the pentose phosphate pathway provides an alternative shunt for hexose monophosphates, like glucose-6-phosphate.

Since glycolysis and the pentose phosphate pathway are directly related, it should help you remember that the pentose phosphate pathway takes place in the cytoplasm.

When examining the pathway in detail, we can break it into two phases: an oxidative phase and a non-oxidative phase.

The oxidative phase is characterized by the oxidation of molecules, starting with of course glucose-6-phosphate. This oxidation is used to reduce NADP+, forming high-energy NADPH molecules. NADPH are distinct and important products of the pentose phosphate pathway, and their formation is a hallmark of the oxidative phase.

The oxidative phase ends with the production of ribulose-5-phosphate, which is the first pentose phosphate produced. In the non-oxidative phase, we’ll touch further on the production of pentose phosphates for which the pathway is named.

The pathway is regulated based on the energy needs of the cell and the body. When NADP levels are high and NADPH levels are low, the pathway is stimulated in an attempt to increase levels of NADPH. Conversely, when NADPH levels are high, the pathway is inhibited.


Key Points

• Pentose Phosphate Pathway (PPP) Oxidative Phase
  • Etymology
    • also called the hexose monophosphate shunt
      • Glucose-6-phosphate (starting substrate) is a hexose ring with 1 phosphate group that is ‘shunted’ from glycolysis to enter the PPP
  • Summary
    • Pentose Phosphate Pathway (PPP) is a metabolic pathway that generates NADPH and precursor molecules for biosynthesis
    • PPP occurs in the cytoplasm
      • Interconnects with glycolysis
        • glycolysis also occurs in the cytoplasm
        • PPP starting substrate, glucose-6-phosphate, is produced by the first step of glycolysis
          • Can be produced in other ways too
    • Two phases
      • Oxidative Phase: generates NADPH
        • energy generating phase: irreversible
          • oxidizes carbon to reduce 2 NADP+ to 2 NADPH
        • NADPH is a reducing agent
        • utilized by cells for numerous functions such as reductive biosynthesis (such as fatty acids and cholesterol) and reducing glutathione
          • NOT the same as NADH
      • Non-oxidative phase: generates precursors for biosynthesis
  • reaction steps (oxidative phase)
    • Glucose-6-phosphate + H2O → [glucose-6-phosphate dehydrogenase] 6-phosphogluconate
      • Intermediate: 6-phosphogluconolactone
        • Lactone ring has an ester group as a result of the oxidation of glucose-6-phosphate
        • Lactonase catalyzes conversion to final product via hydrolysis reaction
      • Reduces NADP+ to NADPH
      • Irreversible rate-limiting step (regulatory site)
    • 6-phosphogluconate → [6-phosphogluconate dehydrogenase] ribulose-5-phosphate
      • Produces CO2
        • Loss of 1 Carbon as CO2 allows it to go from a 6 carbon chain to a 5 carbon chain
      • Produces NADPH
      • Irreversible
      • Ribulose-5-phosphate enters the non-oxidative phase of the pentose phosphate pathway
  • Regulation
    • Regulation is based on energy supply and NADPH demand
      • PPP is anabolic and therefore upregulated when there is plenty of sugar
    • Glucose-6-phosphate dehydrogenase reaction is the primary regulatory step
    • PPP speeds up (upregulation of glucose-6-phosphate dehydrogenase)
      • High energy supply
        • Insulin
          • Release is stimulated by rising blood glucose levels
      • High need for NADPH 
        • NADP+
    • PPP slows down (downregulation of glucose-6-phosphate dehydrogenase)
      • Low need for NADPH
        • NADPH