Pentose Phosphate Pathway (PPP)

• Overview

  • The Pentose Phosphate Pathway (PPP) begins with a common compound: Glucose 6-phosphate (G6-P).

  • The pathway serves two mission-critical functions:

  1. Production of Ribose 5-phosphate (R5-P)

     • R5-P is essential for synthesizing RNA, DNA, and cofactors.

     • Particularly important for rapidly dividing cells.

  2. Synthesis of NADPH

     • NADPH is formed from NADP+ and acts as an electron carrier similar to NADH.

     • Functions of NADPH include:

       • Synthesis of fatty acids.

       • Prevention and reversal of oxidative damage (e.g., in red blood cells).

• Tuning of the PPP:

  • The PPP can be adjusted to concentrate on either of the following outputs:

  • Mostly produce R5-P

  • Mostly produce NADPH

Schematic Overview

• Pathway Overview

  • The pathway consists of both oxidative and non-oxidative reactions:

  • Oxidative reactions include conversion of G6-P into NADPH.

    • $ext{G6-P} + NADP^+ <br>ightarrow NADPH + H^+ + CO_2$

  • Non-oxidative reactions primarily involve transformations of ribulose 5-phosphate (R5-P) into other pentose sugars (e.g., ribose 5-phosphate, xylulose 5-phosphate).

Non-Oxidative Reactions

• Educational Importance

  • The non-oxidative reactions are noted to be "fantastically educational" but do not require memorization.

  • They utilize C-C bond making and breaking mechanisms previously discussed.

  • Key mechanisms involved include:

    1. Schiff base

    2. Thiamine pyrophosphate (TPP)

• Big Picture

  • The first reaction is best represented by the equation:

  • 5C + 5C → 7C + 3C

  • This reaction is analogous to those seen in human aldolase and pyruvate decarboxylase.

• Representation of Non-Oxidative Reactions

  • The non-oxidative phase features specific reactions leading to transformations of various sugars including ribulose 5-phosphate and ribose 5-phosphate.

Enzyme Mechanisms in Non-Oxidative Reactions

• Types of Enzymes

  • The non-oxidative reactions utilize two types of enzymatic mechanisms:

  1. Transketolases

     • Function:

       • Transfer 2-carbon units from ketose (like xylulose 5-phosphate) to aldose (like ribose 5-phosphate).

     • Co-enzyme used: Thiamine pyrophosphate (TPP).

  2. Transaldolases

     • Function:

       • Transfer 3-carbon units.

     • Utilize a Schiff base intermediate during the transfer process.

• Reaction Mechanism Description

  • During the transfer process:

  • The recipient of the 2C or 3C unit is always the aldose variant whose C=O (carbonyl) site acts as the electrophile.

  • The nucleophile in these reactions is represented as follows:

    1. For Transketolases:

    • Nucleophile comes from a 2C fragment.

    1. For Transaldolases:

    • Nucleophile is represented as a 3C fragment prior to transfer, shown as:

      • $CH_2OH + C = NH-Lys-Enz$ (indicating the lysine side-chain involved).

• Carbanion Resonance Forms

  • In both types of reactions, carbanion resonance forms are emphasized to highlight the nucleophilic carbon involved in the reactions.

• Conclusion of Reactions

  • The major reactions outlined above set the stage for understanding how PPP aids in biosynthesis processes including the generation of both ribose sugars and NADPH, showcasing the versatile nature of glucose metabolism through the PPP.