Pentose Phosphate Pathway

The Pentose Phosphate Pathway

• Overview of Growth Requirements

  • Growth is a complex biochemical process requiring:
  • Ribose Sugars: Essential for nucleic acid synthesis.
  • Biochemical Reducing Power (NADPH): Necessary for biosynthetic reactions.

• Sections of the Pathway

  • 26.1 NADPH and Five-Carbon Sugars
  • 26.2 Coordination with Glycolysis and Gluconeogenesis
  • 26.3 Role of Glucose 6-Phosphate Dehydrogenase in Oxidative Stress

26.1 The Pentose Phosphate Pathway Yields NADPH and Five-Carbon Sugars

• Function of the Pathway

  • Converts glucose 6-phosphate into:
  • NADPH: Used in various biochemical processes (e.g., fatty acid and cholesterol biosynthesis).
  • Five-Carbon Sugars: Required for DNA, RNA, and nucleotide synthesis.

• Pathway Stages

  1. Oxidative Phase:
     • Conversion of glucose 6-phosphate leads to NADPH production.
  2. Nonoxidative Phase:
     • Interconversion of sugars to regenerate intermediates.

• Pathways Requiring NADPH:

  • Fatty acid and cholesterol biosynthesis
  • Neurotransmitter and nucleotide biosynthesis
  • Detoxification processes

26.2 Metabolism in Context: Glycolysis and Pentose Phosphate Pathway Coordination

• Link Between Pathways
  • The pathways are integrated through glucose 6-phosphate, which can either enter glycolysis or the pentose phosphate pathway depending on cellular needs.
  • Control Mechanisms:
  • Key Enzyme: Glucose 6-Phosphate Dehydrogenase is the rate-limiting step, activated by NADP+ and inhibited by NADPH.
  • Modes of Metabolic Processing:
  • Mode 1: High ribose 5-phosphate demand (e.g., rapidly dividing cells) leads to conversion via glycolysis.
  • Mode 2: Balanced demand for NADPH and ribose 5-phosphate.
  • Mode 3: High NADPH demand (e.g., liver). Full oxidative consumption of glucose 6-phosphate.
  • Mode 4: Both NADPH and ATP needed; ribulose 5-phosphate converted to pyruvate.

26.3 Role of Glucose 6-Phosphate Dehydrogenase in Oxidative Stress

• Significance of NADPH

  • Protects against reactive oxygen species (ROS) by regenerating reduced glutathione (GSH).
  • GSH combats oxidative stress, essential in various tissues (e.g., red blood cells).

• Deficiency Effects:

  • Individuals lacking G6PD are sensitive to oxidative stress, leading to conditions like hemolytic anemia when exposed to oxidative drugs.

• Clinical Insights:

  • G6PD Deficiency: Often asymptomatic but can be serious when under oxidative stress. Found frequently in Mediterranean populations due to genetic advantages against malaria.

• General Summary: The pentose phosphate pathway provides essential ribose sugars and NADPH, plays a critical role in managing oxidative stress, and highlights the complexity of metabolic regulation within cells.