Pentose Phosphate Pathway (PPP) Lecture

Importance of PPP

• Takes place in the cytoplasm
• Two main reasons for importance:
  1. Generation of 5-carbon pentose sugars:
     • Used to produce DNA, RNA, ATP, NADH, FADH2, and coenzyme A
  2. Production of reducing agent NADPH:
     • Used in biosynthetic processes (e.g., fatty acids, cholesterol, nucleotides)
     • Involved in detoxification processes

Oxidative Phase of PPP

• Focus of this lecture
• Main activities:
  • Oxidation of glucose
  • Release of CO2
  • Generation of NADPH

Step-by-Step Breakdown of the Oxidative Phase

Step 1: Dehydrogenation

• Enzyme: Glucose 6-phosphate dehydrogenase
• Substrate: Glucose 6-phosphate
• Reaction:
  • NADP+ acts as an electron acceptor
  • Two electrons and an H+ ion are extracted from glucose 6-phosphate
  • Generates NADPH and 6-phosphoglucono-δ-lactone
• Significance:
  • Formation of NADPH (reducing agent)
  • Formation of an intramolecular ester bond (to be broken in step 2)

Step 2: Hydrolysis

• Enzyme: Lactonase
• Reaction: Opens the ring structure of 6-phosphoglucono-δ-lactone via hydrolysis
• Product: 6-phosphogluconate
• Preparation for next step: Molecule is now ready for decarboxylation

Step 3: Oxidative Decarboxylation

• Enzyme: 6-phosphogluconate dehydrogenase
• Reaction: Oxidation and decarboxylation of 6-phosphogluconate
  • Removal of carbon 1 (and its associated oxygens) to form CO2
  • Generation of NADPH and ribulose 5-phosphate
• Outcome: Net production of 2 NADPH molecules from one glucose 6-phosphate

Step 4: Isomerization

• Enzyme: Phosphopentose isomerase
• Reaction: Converts ribulose 5-phosphate (ketose) into ribose 5-phosphate (aldose)

Summary of the Oxidative Phase

• Four main steps:
  1. Oxidation-reduction reaction forming NADPH
  2. Hydrolysis opening the ring structure
  3. Oxidative decarboxylation forming another NADPH and releasing CO2
  4. Isomerization converting ribulose 5-phosphate to ribose 5-phosphate
• Outcome: Generation of necessary molecules for cell functions and biosynthesis
• Preparation for the non-oxidative phase in subsequent lectures